Diagnostic and therapeutic insights in individuals with persistent post-dural puncture headache: A cross-sectional study.

BACKGROUND: Post-dural puncture headache (PDPH) is a frequent complication following lumbar puncture, epidural analgesia, or neuraxial anesthesia. The International Classification of Headache Disorders, third edition categorizes PDPH as a self-limiting condition; however, emerging evidence, including our findings, suggests that PDPH can have a prolonged course, challenging this traditional view. OBJECTIVES: To elucidate the diagnostic characteristics and treatment outcomes of persistent PDPH (pPDPH), offering insights into its demographic profiles and diagnostic features. METHODS: We executed an anonymous, web-based survey targeting individuals aged ≥18 years diagnosed with or suspected of having pPDPH. Recruitment occurred through self-help groups on Facebook. The survey comprised questions regarding diagnostic procedures, treatment regimens, outcomes, and healthcare consultation. RESULTS: The survey achieved a response rate of 179/347 (51.6%) individuals completing the questionnaire. Cerebrospinal fluid (CSF) leaks were confirmed in nine of 179 (5.0%) cases. Signs of intracranial hypotension without a CSF leak were observed in 70/179 (39.1%) individuals. All participants underwent magnetic resonance imaging scans of the brain and spine, with computed tomography myelography performed in 113/179 (63.1%) cases. Medications, including analgesics, theophylline, and gabapentin, provided minimal short-term relief. Epidural blood patch treatments resulted in slight-to-moderate short-term improvement in 136/179 (76.0%), significant improvement in 22/179 (12.3%), and complete effectiveness in eight of 179 (4.5%) individuals. For long-term outcomes, slight-to-moderate improvement was reported by 118/179 (66.0%) individuals. Surgical interventions were carried out in 42/179 (23.5%) patients, revealing pseudomeningoceles intraoperatively in 20/42 (47.6%) individuals. After surgery, 21/42 (50.0%) of the participants experienced slight-to-moderate improvement, 12/42 (28.6%) showed more pronounced improvement, and five of the 42 (11.9%) achieved complete effectiveness. CONCLUSION: This study underscores the complexities of managing pPDPH. The delay in diagnosis can impact the effectiveness of treatments, including epidural blood patch and surgical interventions, resulting in ongoing symptoms. This underscores the importance of tailored and adaptable treatment strategies. The findings advocate for additional research to deepen the understanding of pPDPH and improve long-term patient outcomes.

Conventional clinical signs and symptoms are poor predictors of postoperative cerebrospinal fluid leak: A single-centre cohort perspective.

BACKGROUND: Postoperative cerebrospinal fluid (CSF) leak remains a concerning complication of the endoscopic endonasal approach (EEA) for skull base pathology. Signs and symptoms suggesting CSF leak often trigger additional workup during the postoperative course. We systematically evaluate associations between subjectively reported clinical signs/symptoms noted during the immediate postoperative period and incidence of postoperative CSF leaks. METHODS: Retrospective chart review was conducted at a tertiary academic medical centre including 137 consecutive patients with intraoperative CSF leak during EEA with primary repair between July 2018 and August 2022. Postoperative CSF leak associations with clinical signs and symptoms were evaluated using positive (PPV) and negative predictive values (NPV), sensitivity, specificity and odds ratio (OR) via univariate logistic regression. RESULTS: Seventy-nine patients (57.7%) had high-flow leaks repaired and 5 (3.6%) developed CSF leaks postoperatively. Of reported symptoms, rhinorrhea was most common (n = 52, 38.0%; PPV [95% CI] = 7.6% [4.8%, 11.9%]), followed by severe headache (n = 47, 34.3%; 6.3% [3.1%, 12.5%]), dizziness (n = 43, 31.4%; 2.3% [0.4%, 12.1%]), salty or metallic taste (n = 20, 14.6%; 9.9% [3.3%, 25.8%]), and throat drainage (n = 10, 7.3%; 9.9% [1.7%, 41.4%]). Nausea or vomiting constituted the most reported sign concerning for CSF leak (n = 73, 53.3%; PPV [95% CI] = 4.1% [2.0%, 8.1%]). On univariate regression, no sign or symptom, including rhinorrhea (OR [95% CI] = 7.00 [0.76-64.44]), throat drainage (3.42 [0.35-33.86]), salty/metallic taste (4.22 [0.66-27.04]), severe headache (3.00 [0.48-18.62]), dizziness (0.54 [0.06-4.94]), fever (3.16 [0.50-19.99]), and nausea/vomiting (1.33 [0.22-8.21]), associated with postoperative CSF leak. CONCLUSIONS: A range of subjectively reported symptoms and signs failed to predict postoperative CSF leak. Further investigation is warranted to inform appropriate attention and response.

Diagnostic accuracy of intrathecal fluorescein versus other radiological modalities in evaluating non-congenital skull base defects: a systematic review and meta-analysis.

PURPOSE: The intraoperative detection of cerebrospinal fluid (CSF) leaks during endoscopic skull base surgery is critical to ensure watertight sealed defects. Intrathecal fluorescein (ITF) is a valuable adjunct to intraoperative investigation. Hence, our aim is to summarize the evidence of the efficacy of ITF as an accurate diagnostic modality and reconstruction guide for non-congenital skull base defects. METHODS: Using the Cochrane Central, MEDLINE, and Embase databases, we identified studies involving the use of ITF in non-congenital CSF leaks which were published until November 2023. The STATA 18 software was used for meta-analysis. RESULTS: Fourteen studies met the inclusion criteria, in which seven studies were included in the meta-analysis. ITF was used in 1898 (90.3%) of patients, with a detection rate of 88.1%. The overall detection rate of non-congenital CSF leaks among ITF concentrations of 5% and 10% had a statistically significant pooled effect size of 2.6 (95% CI = 2.25, 2.95), while when comparing the ITF to other alternative radiological tests, it was not statistically significant with a mean difference of 0.88 (95% CI = - 0.4, 2.16). Moreover, the pooled prevalence was statistically significant in regards of the complications associated with ITF with an effect size of 0.6 (95% CI = 0.39, 0.82), indicating that 60% of patients who underwent ITF would experience at least one of the measured complications. CONCLUSION: ITF is considered as an efficient tool in localizing skull base defects. However, there was no significant results when comparing the ITF to other alternative radiological tests. Accordingly, if the ITF intervention is indicated, patients should be carefully selected based on their clinical need.

Development and Clinical Validation of a Hook Effect-Based Lateral Flow Immunoassay Sensor for Cerebrospinal Fluid Leak Detection.

BACKGROUND AND OBJECTIVES: Rapid detection of cerebrospinal fluid (CSF) leaks is vital for patient recovery after spinal surgery. However, distinguishing CSF-specific transferrin (TF) from serum TF using lateral flow immunoassays (LFI) is challenging due to their structural similarities. This study aims to develop a novel point-of-care diagnostic assay for precise CSF leak detection by quantifying total TF in both CSF and serum. METHODS: Capitalizing on the substantial 100-fold difference in TF concentrations between CSF and serum, we designed a diagnostic platform based on the well-known "hook effect" resulting from excessive analyte presence. Clinical samples from 37 patients were meticulously tested using the novel LFI sensor, alongside immunofixation as a reference standard. RESULTS: The hook effect-based LFI sensor exhibited outstanding performance, successfully discriminating positive clinical CSF samples from negative ones with remarkable statistical significance (positive vs negative t -test; P = 1.36E-05). This novel sensor achieved an impressive 100% sensitivity and 100% specificity in CSF leak detection, demonstrating its robust diagnostic capabilities. CONCLUSION: In conclusion, our study introduces a rapid, highly specific, and sensitive point-of-care test for CSF leak detection, harnessing the distinctive TF concentration profile in CSF compared with serum. This novel hook effect-based LFI sensor holds great promise for improving patient outcomes in the context of spinal surgery and postsurgical recovery. Its ease of use and reliability make it a valuable tool in clinical practice, ensuring timely and accurate CSF leak detection to enhance patient care.

The cervical blood patch: A therapeutic "miraculous" for cerebrospinal fluid leaks: A case report.

RATIONALE: Cerebrospinal fluid (CSF) leaks, arising from abnormal openings in the protective layers surrounding the spinal cord and brain, are a significant medical concern. These leaks, triggered by various factors including trauma, medical interventions, or spontaneous rupture, lead to the draining of CSF-an essential fluid safeguarding the nervous system. A classic symptom of CSF leaks is an incapacitating headache exacerbated by sitting or standing but relieved by lying down. Spontaneous intracranial hypotension (SIH) denotes the clinical condition marked by postural headaches due to spontaneous CSF leakage and hypotension, often misdiagnosed or underdiagnosed. While orthostatic headaches are the hallmark, SIH may manifest with an array of symptoms including nausea, tinnitus, hearing loss, visual disturbances, and dizziness. Treatment options encompass conservative measures, epidural blood patches (EBP), and surgery, with EBP being the primary intervention. PATIENT CONCERN: The patient did not express any specific concerns regarding their medical diagnosis. However, they did harbor apprehensions that their condition might necessitate surgical intervention in the future. DIAGNOSIS: The patient had been treated with antibiotics with a pre-diagnosis of sinusitis and was admitted to the neurology department of our hospital when his symptoms failed to improve. Cranial magnetic resonance imaging was interpreted as thickening of the dural surfaces and increased contrast uptake, thought to be due to intracranial hypotension. Cranial MR angiography was normal. Full-spine magnetic resonance imaging revealed a micro-spur at the C2 to 3 level and the T1 to 2 level in the posterior part of the corpus. INTERVENTIONS: The cervical EBP was performed in the prone position under fluoroscopic guidance. There were no complications. OUTCOMES: The patient was invited for follow-up 1 week after the procedure, and control examination was normal. LESSONS: SIH poses a diagnostic challenge due to its diverse clinical presentation and necessitates precise imaging for effective intervention. Cervical EBP emerges as a promising treatment modality, offering relief and improved quality of life for individuals grappling with this condition. However, clinicians must carefully assess patients and discuss potential risks and benefits before opting for cervical blood patches.

Cerebrospinal Fluid Refill Test as a Novel Diagnostic Tool for Cerebrospinal Fluid Hypovolemia: Preliminary Result.

OBJECTIVE: Cerebrospinal fluid (CSF) hypovolemia presents with orthostatic headaches due to CSF leakage. However, a direct association between the lack of CSF and clinical symptoms has not been found. CSF hypovolemia can be improved by refilling CSF. Therefore, we assessed the validity of a CSF refill test. METHODS: From November 2019 to August 2021, we included 10 patients (≥18 years old) with potential CSF hypovolemia, clear orthostatic headaches, and a CSF opening pressure <10 cmH2O. In the CSF refill test, 10 mL of artificial CSF was injected intrathecally. The primary outcome was improvement in orthostatic headache assessed using a visual analog scale (VAS), while the secondary outcomes were the 10-m walk time and adverse events. When the symptoms temporarily improved after intrathecal injection, the patients underwent radiologic imaging to identify the CSF leak, and an epidural blood patch was proposed accordingly. RESULTS: All patients showed post-test improvements in the VAS score (median [interquartile range], pretest 63.0 [50.3-74.3] vs. post-test 1.5 [0.0-26.0]). The 10-m walk time also significantly improved (9.5 [8.5-10.2] s vs. 8.2 [7.9-8.7] s). One patient experienced temporary right leg numbness associated with a lumbar puncture. After radiologic investigation, 9 patients underwent epidural blood patches, of which 6 were completely cured, and 3 revealed partial improvement. CONCLUSIONS: The cerebrospinal fluid (CSF) refill test was safe and effective in demonstrating the direct association between the lack of CSF and clinical symptoms and may help predict the outcome of an epidural blood patch.

Spontaneous Cerebrospinal Fluid Leak in a Patient with Asymptomatic Idiopathic Intracranial Hypertension.

BACKGROUND: Spontaneous cerebrospinal fluid (CSF) leaks occur when there is a tear in the dura mater. Spontaneous CSF leaks are rare, and often associated with conditions like intracranial hypertension, connective tissue disorders, or congenital defects in the dura mater. CASE REPORT: The patient was a 66-year-old woman who presented to the Emergency Department with clear, positional nasal discharge from her left nostril for 1 week. She had a history of chronic headaches, which seemed to have been relieved around the time of onset of her rhinorrhea. Diagnostic imaging, including computed tomography and magnetic resonance imaging scans, confirmed the presence of a CSF leak and a left temporal meningoencephalocele. The patient subsequently underwent surgical repair of the leak and ventriculoperitoneal shunt placement, and was discharged home in stable condition. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Early detection of CSF leaks require a thorough history and physical examination, and is crucial in preventing potentially life-threatening complications such as meningitis and intracranial abscesses.

Multiple skull base defects in the setting of spontaneous cerebrospinal fluid rhinorrhea; a dual institution view.

PURPOSE: Idiopathic intracranial hypertension (IIH) is a condition of high cerebrospinal fluid (CSF) pressure that presents with CSF leak. The implications of multiple skull base defects (SBD) and associated synchronous CSF leaks have not been previously explored. MATERIALS AND METHODS: A dual institutional case-control study examined multiple SBD's and encephaloceles on the risk of CSF leak and postoperative failures post-repair. IIH patients with CSF leaks and IIH controls without leaks were selected retrospectively. Chi square analysis evaluated for statistically significant alterations in probability with CSF leak development. RESULTS: 192 patients were selected with 108 IIH controls and 84 spontaneous CSF leak cases. Signs and symptoms for IIH controls and CSF leak cases respectively were pulsatile tinnitus (60.2 % and 29.8 %), headaches (96.3 % and 63.1 %), papilledema (74.1 % and 12.5 %), visual field defects (60.8 % and 13 %) (p < 0.001). Encephalocele formation in controls was 3.7 % compared to cases at 91.6 % (p < 0.001). Multiple SBD's in controls compared cases was 0.9 % and 46.4 % respectively (p < 0.001). Subgroup analysis of CSF leak cases showed 15 patients with two CSF leak repairs due to a recurrence. 27 (39.1 %) single leak cases had multiple SDB's while 12 (80 %) recurrent leaks had multiple SDB's (p = 0.004). CONCLUSIONS: Patients with radiographic evidence of multiple SBD's and encephaloceles represent a high-risk population with a propensity for CSF leaks. Secondary SBD's are common in patients with spontaneous CSF rhinorrhea and higher in patients with a recurrence.

Case Report: Unilateral Cranial Nerve VI Palsy Secondary to Intracranial Hypotension.

SIGNIFICANCE: Intracranial hypotension is a condition that occurs from a cerebrospinal fluid leak. Various visual symptoms have been associated with this condition. Cranial nerve VI (CN VI) palsies are the most common ocular manifestation, as the abducens nerve is prone to injury because of its intracranial anatomical course. PURPOSE: This case report presents a CN VI palsy secondary to intracranial hypotension from ventriculoperitoneal shunt overfiltration. Diagnosis, treatment, and management considerations are discussed. No identifiable health information was included in this case report. CASE REPORT: A 70-year-old White man was referred to the eye clinic for evaluation of binocular horizontal diplopia. The patient had a recent history of a left ventriculoperitoneal shunt for a persistent cerebrospinal fluid leak after complex mastoid surgery. The patient was also symptomatic for positional headaches, which improved in a recumbent position. He was diagnosed with a left CN VI palsy secondary to intracranial hypotension from a ventriculoperitoneal shunt overfiltration. The patient was followed up by neurosurgery for shunt adjustments to resolve the overfiltration. Binocular horizontal diplopia was managed conservatively with Fresnel prism. CONCLUSIONS: Intracranial hypotension should be considered in patients presenting with cranial nerve palsies and positional headaches. Obtaining neuroimaging and comanaging with neurology or neurosurgery are advised to make prompt diagnosis and treatment. Careful clinical monitoring and conservative diplopia therapy are recommended as visual symptoms improve upon resolution of the cerebrospinal fluid leak.

[SPONTANEOUS CEREBROSPINAL FLUID LEAK OF THE TEMPORAL BONE].

INTRODUCTION: Spontaneous cerebrospinal fluid (CSF) leak into the temporal air spaces is a prominent risk factor for meningitis, often leading to debilitating neurological morbidities and even death. CSF leaks may arise due to trauma, congenital malformation, or surgery, but in most cases, they develop spontaneously. In spontaneous CSF leaks, no obvious triggering event is apparent in the patient's clinical history that points to this diagnosis, in contrast to some of the other etiologies. The clinical presentation of spontaneous CSF leaks is not unique and is characterized by patients' complaints, such as hearing loss and aural fullness. These symptoms are commonly associated with prevalent conditions, such as serous otitis media. For these reasons, a typical diagnostic delay of spontaneous CSF leaks, which can last for years in some cases, leaves the patients exposed to meningeal infection without being offered an efficient surgical treatment to keep them safe and protected.

Spontaneous intracranial hypotension: updates from diagnosis to treatment.

Spontaneous intracranial hypotension (SIH) is caused by spinal cerebrospinal fluid (CSF) leaks, which result in continued loss of CSF volume and multiple debilitating clinical manifestations. The estimated annual incidence of SIH is 5/100,000. Diagnostic methods have evolved in recent years due to improved understanding of pathophysiology and implementation of advanced myelographic techniques. Here, we synthesize recent updates and contextualize them in an algorithm for diagnosis and treatment of SIH, highlighting basic principles and points of practice variability or continued debate. This discussion includes finer points of SIH diagnosis, CSF leak classification systems, less common types and variants of CSF leaks, brain MRI Bern scoring, potential SIH complications, key technical considerations, and positioning strategies for different types of dynamic myelography. The roles of conservative measures, non-targeted or targeted blood patches, surgery, and recently developed endovascular techniques are presented.

Presumptive Idiopathic Intracranial Hypertension Based on Neuroimaging Findings: A Referral Pattern Study.

BACKGROUND: Radiologic findings of intracranial hypertension (RAD-IH) are common in idiopathic intracranial hypertension (IIH) patients. Paralleling the increasing rates of obesity, the burden of IIH is growing. Urgent neuro-ophthalmology consultations for possible IIH in patients with incidentally detected RAD-IH are increasing, with many patients receiving unnecessary lumbar punctures (LPs) and treatments. This retrospective observational study aimed to determine the prevalence of neuro-ophthalmology consultations for RAD-IH, rate of funduscopic examination by referring providers, prevalence of papilledema, outcomes after neuro-ophthalmic evaluation, and rates of misdiagnosis. METHODS: Records of 1,262 consecutive new patients seen in one neuro-ophthalmology clinic from January 2019 to January 2020 were reviewed. We identified patients who were: 1) referred with concern for IIH because of findings of RAD-IH; 2) referred for "papilledema"; 3) referred with a diagnosis of IIH; and 4) referred for spontaneous cranial cerebrospinal fluid (CSF) leaks. In addition to basic demographic profiles for all groups, detailed information was collected for patients referred solely for RAD-IH, including referral patterns, prior history of IIH, previous LPs, prior medical or surgical treatment(s), risk factors for increased intracranial pressure (ICP), presenting symptoms, radiologic features observed on neuroimaging, and final disposition. When available, the neuroimaging was reviewed by an expert neuroradiologist. RESULTS: Of 1,262 consecutive new patients, 66 (5%) were referred specifically for RAD-IH; most referrals came from neurologists (58%); 8/66 (12%) patients had papilledema; 16/66 (24%) patients had prior LP and 13/66 (20%) were already treated based on MRI findings; and 22/66 (33%) patients had ≤2 RAD-IH. Only 34/66 (52%) of patients referred for RAD-IH had prior funduscopic examinations. We confirmed papilledema in 26/82 (32%) patients referred for "papilledema." Only 29/83 (35%) patients referred with a diagnosis of IIH had active papilledema, and 3/16 (19%) patients with spontaneous CSF leaks had papilledema. In total, 247/1,262 (20%) new patients were referred to our clinic over 1 year with concern for IIH, among whom only 66 (27%) were confirmed to have active IIH with papilledema. CONCLUSIONS: One in 5 new patient referrals seen in our neuro-ophthalmology clinic were referred because of concern for increased ICP, but only 1/4 had active papilledema. Most patients referred for isolated RAD-IH do not have papilledema, many having undergone unnecessary LPs and treatments. The burden of these "rule-out IIH" consultations is overwhelming and will only continue to increase with the concurrent rise of obesity and IIH, straining the already limited neuro-ophthalmologic resources available in the US.

Expanding the clinical spectrum of idiopathic intracranial hypertension.

PURPOSE OF REVIEW: Idiopathic intracranial hypertension (IIH) is a disorder of raised intracranial pressure (ICP). Although the majority of patients with IIH present classically with headache and papilledema, some patients may have unusual presentations or manifestations. Recent advancements in neuroimaging have facilitated the identification of other presentations associated with IIH. This review provides an overview of the expanding clinical spectrum of IIH. RECENT FINDINGS: Presentations of IIH that are considered unusual include highly asymmetric or unilateral papilledema, IIH without papilledema, and IIH associated with cranial nerve involvement. These presentations likely reflect differences in the way cerebrospinal fluid (CSF) pressure is transmitted intracranially. Radiological signs of intracranial hypertension are increasingly recognized in patients with IIH and provide further insights into the effects of raised ICP on intracranial structures. Osseous changes in the skull base leading to formation of meningoceles and encephaloceles have been identified in patients with IIH, spontaneous skull base CSF leak, and drug-resistant temporal lobe epilepsy, suggesting a possible association. SUMMARY: Clinicians should be familiar with the expanding clinical spectrum of IIH and the implications for the management of these presentations.

A supervised machine-learning algorithm predicts intraoperative CSF leak in endoscopic transsphenoidal surgery for pituitary adenomas.

BACKGROUND: Despite advances in endoscopic transnasal transsphenoidal surgery (E-TNS) for pituitary adenomas (PAs), cerebrospinal fluid (CSF) leakage remains a life-threatening complication predisposing to major morbidity and mortality. In the current study we developed a supervised ML model able to predict the risk of intraoperative CSF leakage by comparing different machine learning (ML) methods and explaining the functioning and the rationale of the best performing algorithm. METHODS: A retrospective cohort of 238 patients treated via E-TNS for PAs was selected. A customized pipeline of several ML models was programmed and trained; the best five models were tested on a hold-out test and the best classifier was then prospectively validated on a cohort of 35 recently treated patients. RESULTS: Intraoperative CSF leak occurred in 54 (22,6%) of 238 patients. The most important risk's predictors were: non secreting status, older age, x-, y- and z-axes diameters, ostedural invasiveness, volume, ICD and R-ratio. The random forest (RF) classifier outperformed other models, with an AUC of 0.84, high sensitivity (86%) and specificity (88%). Positive predictive value and negative predictive value were 88% and 80% respectively. F1 score was 0.84. Prospective validation confirmed outstanding performance metrics: AUC (0.81), sensitivity (83%), specificity (79%), negative predictive value (95%) and F1 score (0.75). CONCLUSIONS: The RF classifier showed the best performance across all models selected. RF models might predict surgical outcomes in heterogeneous multimorbid and fragile populations outperforming classical statistical analyses and other ML models (SVM, ANN etc.), improving patient management and reducing preventable morbidity and additional costs.

Systematic Review: Evaluating the Efficacy of Intrathecal Fluorescein for Localizing Cerebrospinal Fluid Rhinorrhea.

OBJECTIVES: A defect in the skull base can result in leakage of cerebrospinal fluid (CSF) out of the subarachnoid space into the sinonasal cavities, termed CSF rhinorrhea. Patients presenting with CSF rhinorrhea often require surgical repair, typically performed endoscopically. Successful surgical intervention is highly reliant on accurate identification of the leak site. Identification can be enhanced by the administration of intrathecal fluorescein (IF) via a lumbar drain before surgery. The objective of this systematic review is to better characterize the benefits and limitations of IF administration. METHODS: A systematic search was conducted for literature documenting the use of IF for CSF leak localization. The results of this search were subjected to initial review, followed by full-text evaluation of selected texts, and final inclusion based on predetermined selection criteria. Primary outcomes were specificity and sensitivity of IF administration in identifying CSF leak sites. Secondary outcomes included administration technique and safety data. RESULTS: A total of 25 studies representing 3801 instances of IF administration met inclusion criteria. When injected slowly for up to 30 minutes at doses of <50 mg, IF administration results in minimal complications. A total of 25 mg doses (92.36%) of IF appear more sensitive than 10 mg (71.88%) doses of IF while maintaining a similar safety profile. Mixing fluorescein with double distilled water instead of CSF or saline may decrease waiting times before fluorescein can be identified and increase its safety profile. CONCLUSIONS: Intrathecal fluorescein may play an important role in the identification of CSF leak site during endoscopic repair.

Low Preoperative Prealbumin Levels Are a Strong Independent Predictor of Postoperative Cerebrospinal Fluid Leak Following Endoscopic Endonasal Skull Base Surgery.

OBJECTIVE: Prealbumin levels correlate with overall nutritional status, and low values are associated with poor wound healing. We investigated whether low preoperative prealbumin levels predict risk of endoscopic endonasal skull base surgery (EESBS) reconstruction failure, as demonstrated by postoperative cerebrospinal fluid (CSF) leak and/or infection. METHODS: Between October 2018 and February 2020, 98 patients with documented preoperative prealbumin levels were prospectively followed. The incidence of CSF leak and infection in patients with low prealbumin levels (≤20 mg/dL) was compared with those with normal prealbumin levels (>20 mg/dL). Numerous factors previously shown to influence CSF leak rates were assessed. Both univariate and multivariable analyses were performed to identify independent predictive factors. RESULTS: Within this prospectively gathered patient cohort composed of >95% "high-risk" expanded EESBS, 14 of 98 patients (14.3%) experienced a postoperative CSF leak. Factors univariately associated with postoperative complications at the 0.2 level of significance were used in a multivariable model. Low prealbumin levels (≤20 mg/dL) proved to be a strong independent predictive factor associated with a 5-fold increased risk of postoperative CSF leak (odds ratio 5.01, P = 0.01), and postoperative surgical-site infection (P = 0.0009). These associations remained after controlling for multiple other factors, including body mass index, surgical pathology, previous EESBS, risk assessment index, and high- versus low-flow intraoperative CSF leaks. CONCLUSIONS: Preoperative prealbumin levels are an independent predictor of EESBS associated CSF leak and infection. Future studies are needed to investigate the utility of screening and correcting prealbumin levels to limit postoperative complications.

Evaluate the safety and efficacy of dura sealant patch in reducing cerebrospinal fluid leakage following elective cranial surgery (ENCASE II): study protocol for a randomized, two-arm, multicenter trial.

BACKGROUND: Cerebrospinal fluid (CSF) leakage is a frequent and challenging complication in neurosurgery, especially in the posterior fossa, with a prevalence of 8%. It is associated with substantial morbidity and increased healthcare costs. A novel dural sealant patch (LIQOSEAL) was developed for watertight dural closure. The objective of this study is to clinically assess the safety and effectiveness of LIQOSEAL as a means of reducing intra- as well as postoperative CSF leakage in patients undergoing elective posterior fossa intradural surgery with a dural closure procedure compared to the best currently available dural sealants. METHODS: We will conduct a two-arm, randomized controlled, multicenter study with a 90-day follow-up. A total of 228 patients will be enrolled in 19 sites, of which 114 will receive LIQOSEAL and 114 an FDA-approved PEG sealant. The composite primary endpoint is defined as intraoperative CSF leakage at PEEP 20 cm H2O, percutaneous CSF leakage within 90 days of, wound infection within 90 days of or pseudomeningocele of more than 20cc on MRI or requiring intervention. We hypothesize that the primary endpoint will not be reached by more than 10 patients (9%) in the investigational arm, which will demonstrate non-inferiority of LIQOSEAL compared to control. DISCUSSION: This trial will evaluate whether LIQOSEAL is non-inferior to control as a means of reducing CSF leakage and safety TRIAL REGISTRATION: ClinicalTrials.gov NCT04086550 . Registered on 11 September 2019.

Quantitative lateral flow immunoassay for rapid detection and monitoring of cerebrospinal fluid leakage following incidental durotomy.

Cerebrospinal fluid (CSF) leakage due to incidental durotomy is an inherent complication of spine surgery. With appropriate treatment, complications of CSF leakage, such as headache and even meningitis, can be reduced. CSF leakage could be detected on the basis of correlated clinical symptoms; diagnosis should be based on these symptoms and appropriate imaging studies. However, the diagnosis of CSF leakage remains a challenge, especially if incidental durotomy is unrecognized during surgery; even if incidental durotomy is detected and repaired intraoperatively, the severity of the leakage and quality of the primary dural repair are difficult to evaluate postoperatively. Rapid, inexpensive, and safe methods of detecting CSF-containing samples are currently lacking; hence, the development of a point-of-care test (POCT) method to improve diagnostic efficiency is necessary. We developed a high-sensitivity lateral flow immunoassay with a stacking pad (sLFIA) for quantitative detection of ß-trace protein (BTP), a specific CSF marker. The BTP concentration in 39 clinical samples was calculated using a calibration equation for test-line intensity and evaluated by a standard laboratory method. To avoid the hook effect, we diluted each sample prior to testing. The correlation coefficient between the enzyme-linked immunosorbent assay and our BTP sLFIA method was 0.991 A 75-fold sample dilution was applied owing to the hook effect point, identified as 175 ng mL-1. We established an optimal sample-specific cutoff point at a value of 4.0 µg mL-1 for CSF leakage in subfascial drainage samples following spinal posterior decompression. The sensitivity and specificity of the BTP sLFIA method were 90% and 97%, respectively, according to a receiver operating characteristic curve analysis. In addition, clinical samples from patients who underwent primary dural repair intraoperatively were tested, and CSF leakage was successfully diagnosed using our method. Finally, the quantitation of BTP in samples collected daily provided an accurate assessment of the severity of the residual leakage. Our results demonstrate that the BTP sLFIA method possesses the potential to serve as a POCT method for screening and monitoring postoperative CSF leakage.

Can the Risk of Postoperative Cerebrospinal Fluid Leakage Be Predicted for Patients Undergoing Cervical Spine Surgery? Development and Evaluation of a New Predictive Nomogram.

OBJECTIVE: Previous studies have retrospectively analyzed the likely causes of cerebrospinal fluid leakage (CSFL) during cervical spine surgery and the management of CSFL after its occurrence. In the present study, we aimed to develop and validate a nomogram for the risk of CSFL in Chinese patients who had undergone cervical decompression and internal fixation (CDIF) surgery. METHODS: We performed a retrospective analysis of patients who had undergone CDIF surgery. Of the 1286 included patients, 54 were in the CSFL group and 1232 were in the normal group. The patients were randomly divided into training and validation tests. The risk assessment for CSFL included 21 characteristics. The feature selection for the CSFL model was optimized using the least absolute shrinkage and selection operator regression model in the training test. Multivariate logistic regression analysis was performed to construct the model according to the selected characteristics. The clinical usefulness of the predictive model was assessed using the C-index, calibration curve, and decision curve analysis with identification and calibration. RESULTS: The risk prediction nomogram included the diagnosis, revision surgery, ossification of the posterior longitudinal ligament, cervical instability, and a history of malignancy in the training test. The model demonstrated high predictive power, with a C-index of 0.914 (95% confidence interval, 0.876-0.951) and an area under the curve of 0.914. The results of the decision curve analysis demonstrated the clinical usefulness of the CSFL risk nomogram when the probability threshold for CSFL was 1%-62%. CONCLUSIONS: Our proposed nomogram for CSFL risk includes the diagnosis, revision surgery, ossification of the posterior longitudinal ligament, cervical instability, and a history of malignancy. The nomogram can be used to evaluate the risk of CSFL for patients undergoing CDIF surgery.

Color Change of Intranasal Fluorescein Cannot Detect Cerebrospinal Fluid Leaks.

BACKGROUND: The color change of topical intranasal fluorescein has been used to confirm the presence of cerebrospinal fluid (CSF) during endoscopic endonasal surgery. We aimed to validate the use of topical intranasal fluorescein for CSF detection. METHODS: Blood, CSF, saliva, and normal saline were combined with decreasing fluorescein concentrations (from 10% to 0.1%). The solutions were photographed in high definition on nasal pledgets and in 1.5-mL Eppendorf tubes. The color difference (ΔE) was objectively measured via the International Commission on Illumination coordinates. Four otolaryngologists who were unaware of the study parameters also evaluated the samples for perceptible color differences. The human eye cannot detect color differences at an International Commission on Illumination ΔE of <5. RESULTS: All otolaryngologists agreed a color difference could be seen with blood across all fluorescein concentrations. However, a perceptible color difference between the experimental samples that excluded blood was not appreciable. Objectively, the ΔE was <5 on average for all nonblood samples when mixed with 5% and 10% fluorescein in the Eppendorf experiment. The ΔE for the nonblood samples was >5 for the remaining tested. Similarly, the average ΔE for the nonblood samples in the pledget experiment was >5 across all fluorescein concentrations. The blood ΔE was consistently >50 throughout all fluorescein concentrations in the Eppendorf experiment and >20 throughout the pledget experiment, correlating with the subjective ease of discernment between blood and the control sample in both groups. CONCLUSIONS: Color change alone is not sufficient to determine a difference between CSF, saliva, and saline. Blood, however, is readily identified using this method. Adjunct characteristics, in addition to the color change, are necessary to properly identify an active CSF leak.