OBJECTIVE: Recurrent cerebrospinal fluid (CSF) rhinorrhea caused by sequential, anatomically separated skull base defects is rarely reported in the literature. Neither management nor etiology has been sufficiently investigated. We present an illustrative case and a systematic review of the literature regarding etiology, diagnostics, and management of this rare phenomenon.
METHODS: A systematic literature search looking for articles reporting sequential CSF leaks with multiple skull base defects was performed. Data from included articles were descriptively reported, and the quality of the included studies was assessed with Grading of Recommendations Assessment, Development and Evaluation.
RESULTS: A 71-year-old woman with posttraumatic CSF rhinorrhea and left-sided CSF otorrhea due to a left-sided horizontal fracture of the petrous bone presented at our institution. After initial surgical repair and a 10-week symptom-free interval, CSF rhinorrhea recurred. Imaging revealed a preexisting contralateral meningoencephalocele of the lateral sphenoid recess causing recurrent CSF rhinorrhea most likely after initial traumatic laceration. The defect was successfully treated. A literature search identified 366 reports, 6 of which were included in the systematic review with a total of 10 cases. Quality was deemed good in 8 of 10 cases. The most common location for primary and sequential CSF leaks was along the sphenoid bone (4/10 and 5/10 patients, respectively). All publications except one reported the presence of a meningo (encephalo)cele as cause of the sequential CSF leak.
CONCLUSIONS: Occurrence of recurrent CSF rhinorrhea due to an anatomically separated sequential skull base lesion remains a rare phenomenon. Reassessment of imaging studies and a structured diagnostic workup to detect sequential CSF leaks independent of the primary lesion should is recommended.

OBJECTIVE: 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.
CONCLUSIONS: 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.

BACKGROUND: Beta-2 transferrin (B2-Tf) gel electrophoresis (GE) is the preferred non-invasive diagnostic modality for confirming cerebrospinal fluid (CSF) in body fluids. While B2-Tf GE testing is highly sensitive and specific for CSF, false-positive (FP) and false-negative (FN) results can lead to diagnostic and therapeutic dilemmas. Several series have demonstrated potential causes of false B2-Tf GE results, but few studies have reported reasons for these errors. The purpose of this systematic review was to describe sources of B2-Tf GE errors.
METHODS: A systematic review was performed by searching OVID, EMBASE, and Web of Science databases for B2-Tf GE studies. After applying exclusion criteria, original research studies directly addressing erroneous B2-Tf GE results underwent qualitative analysis.
RESULTS: Of the 243 abstracts screened, 71 underwent full-text review and 18 studies reporting B2-Tf GE errors were included for analysis. There were 15 potential FPs, 12 actual FPs, 12 potential FNs, 19 actual FNs, and 14 indeterminate results. There were also 246 potentially indeterminate results from in vitro studies. Reasons for B2-Tf GE errors included serum transferrin alterations (n = 17; all potential), infection related (n = 13; 9 potential), orbital or salivary contamination (n = 2; 1 potential), and collection related (n = 255; 246 potential). There were 31 false or indeterminate results with unspecified reasons. There were no reported errors due to laboratory processing.
CONCLUSIONS: Multiple potential or actual reasons for false or indeterminate results have been reported for B2-Tf GE testing of rhinorrhea and otorrhea. Future studies should explore reasons for B2-Tf testing errors and how these may affect clinical decision making.

OBJECTIVE: To assess existing literature on topical intranasal fluorescein (TINF) for the diagnosis and localization of nasal cerebrospinal fluid (CSF).
METHODS: Systematic review.
METHODS: A 6-database literature search was conducted to identify articles providing insight into TINF for the diagnosis and treatment of sinonasal CSF leak. Demographic characteristics, technical details, efficacy, and safety data were extracted and analyzed. Methodological quality was assessed using Methodological Items for Non-Randomized Studies (MINORS) criteria.
RESULTS: All studies reported a diagnostic accuracy rate ≥96%. There were no major complications reported for any patient (n=99) with either 5% or 10% fluorescein use. The MINORS instrument of methodological quality indicated that the assessed studies were of moderate quality (7.29 out of a maximum score of 24).
CONCLUSIONS: This systematic review indicates that TINF is an easy, safe, inexpensive, and sensitive approach for the diagnosis and treatment of sinonasal CSF leakage. For these reasons, it may be especially well suited for resource-limited clinical scenarios.

BACKGROUND: Idiopathic intracranial hypertension can lead to dural defects and spontaneous leakage of cerebrospinal fluid (CSF) from the skull base. Skull base CSF leaks are rarely reported in pregnancy but pose unique challenges for obstetricians and anesthesiologists.
METHODS: A 31-year-old G4P1021 at 14 weeks developed debilitating headaches and CSF rhinorrhea. Brain imaging revealed a bony defect of the sphenoid sinus with a meningoencephalocele and a partially empty sella, consistent with CSF leakage from a skull base defect. The patient was neurologically stable without signs of meningitis; thus, management was focused on symptomatic alleviation. A planned cesarean section was performed at 38 weeks under spinal anesthesia. The patient had spontaneous marked improvement of her symptoms postpartum.
CONCLUSIONS: Pregnancy may exacerbate skull base CSF leaks, requiring careful management with a multidisciplinary team. Neuraxial anesthesia can safely be performed in pregnant individuals with spontaneous skull base CSF leakage, but further studies are needed to determine the safest mode of delivery in these patients.

The present study aimed to improve the diagnosis and treatment outcome of cerebrospinal fluid (CSF) rhinorrhea caused by patent meningoencephalocele of Sternberg\'s canal of the sphenoid sinus by analyzing the clinical data and imaging features of two rare cases of this disease and by reviewing the relevant literature for possible etiology, diagnoses, and treatments.
Together with the relevant literature, we retrospectively studied the clinical and imaging data of two patients (mother and child) with CSF rhinorrhea caused by patent meningoencephalocele of Sternberg\'s canal of the sphenoid sinus, analyzed their diagnostic and treatment procedures, and proposed a potential, feasible treatment method.
On the 2nd day after surgery, the expansive sponge and iodoform gauze in the nasal cavity were removed in both patients, and the lumbar subarachnoid drainage was removed 3 days after the operation, as no nasal discharge was observed. One week after the operation, head magnetic resonance imaging (MRI) showed that the abnormal tissue in the sphenoid sinus had disappeared, and no accumulation of the CSF was observed. Both patients were discharged after 2 weeks. At the time of discharge, both patients were without nasal drip, fever, headache, and other discomforts, and they had grade 5 muscle strength in their extremities, with normal muscle tension.
CSF rhinorrhea is usually caused by secondary factors. Spontaneous CSF rhinorrhea caused by encephalocele of the skull base due to congenital dysplasia of the skull base is very rare and easily misdiagnosed. The presence of brain tissue or CSF signal in the sphenoid sinus on preoperative MR images is an important imaging feature of the disease. Conditional cisternography can be used to further detect CSF leaks. Endoscopic transnasal transsphenoidal repair of CSF leaks combined with short-term postoperative lumbar subarachnoid drainage is an effective treatment method. According to previous literature, the possible causes of meningoencephalocele with patent Sternberg\'s canal of the sphenoid sinus include abnormal development of the sphenoid sinus or the craniopharyngeal canal and bone defects of the skull base. There are no related reports on patent meningoencephalocele caused by Sternberg\'s canal in direct blood relatives, such as mother-son; therefore, the possibility of this disease having a genetic origin should be considered in future studies on its pathophysiological mechanisms.

OBJECTIVE: 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.

Encephaloceles rarely develop following traumatic skull fractures. Given their low incidence, the clinical presentations and management strategies of these lesions are confined to case reports and limited case series. A systematic literature review was performed using PubMed, Ovid, and Web of Science databases to identify relevant articles using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 37 articles met inclusion criteria, including the case presented herein. These articles reported 52 traumatic encephaloceles. Mean patient age was 25.3 years (range 6 mo-66 y) with a male predominance (63%, 33/52). The most common bony defects resulting in encephalocele formation were the orbital roof (52%, 27/52), ethmoid (35%, 18/52), and sphenoid (10%, 5/52). Mean time from traumatic injury to initial presentation was 21.3 months (range 0 d-36 y) with a bimodal distribution split between immediately following the traumatic injury (57%, 26/46) or in a delayed manner (43%, 20/46). Common presentations of orbital roof, frontonasal, and temporal bone encephaloceles were exophthalmos (85%, 23/27), cerebrospinal fluid rhinorrhea (71%, 17/24), and hearing loss (100%, 4/4), respectively. Operative approach, repair technique, and materials used for encephalocele reduction were highly variable. Surgical intervention afforded definitive symptomatic improvement or resolution in the majority of cases (89%, 42/47). Clinical outcomes did not differ between orbital, frontonasal, or temporal bone encephaloceles ( P =0.438). Traumatic encephaloceles are a rare entity with diverse presenting symptomatology dependent upon the location of fracture dehiscence. Surgical intervention affords symptomatic improvement in the majority of cases irrespective of encephalocele location, time to presentation, or operative approach.

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Endoscopic endonasal eustachian tube obliteration (EEETO) is a valuable option for treating cerebrospinal fluid rhinorrhea (CSFR) after lateral skull base surgery. Several small case series describe different techniques because of the rarity of this indication.
To review available literature on EEETO focusing on technique and factors affecting success. We also contribute a new case series using a knotless barbed suture technique.
This was a retrospective chart review of EEETO using barbed suture for CSFR at our institution from 2018 to 2021. Scoping review was performed by searching PubMed for articles on EEETO for CSFR. Patients were pooled for data syntheses.
Our retrospective series contained 7 patients. Two patients (28.6%) required revision, but all were ultimately successful. Six studies were identified in scoping review for a combined total of 23 patients. Most of the patients initially underwent translabyrinthine (52.2%) resection of vestibular schwannoma (82.6%). Average time to initial CSFR was 362.6 days (standard deviation ± 1034.2, range 0-4320 days). Twenty-two patients underwent lumbar drain, and 11 underwent prior surgical attempts before EEETO. The initial success rate of EEETO was 65.2%. In 8 patients needing revision, EEETO was ultimately successful in 6. There were no differences in demographics or presentation between successful and revision cases. Seven different techniques were described.
EEETO can treat CSFR after lateral skull base surgery. Revision surgery is common and difficult to predict. Several techniques have been described, and utilization of barbed suture is a viable method with comparable success, but without the need for endoscopic knot tying.