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Frontiers in Allergy ·

Volume 7 - 2026 | https://doi.org/10.3389/falgy.2026.1914144

Can negative HRCT locate ethmoid CSF leaks? A retrospective analysis

  • Jie-Wen Zhou1,2,3
  • Xin-Yu Zhang1,2,3
  • Yu-Wen Gong2,3
  • Jing-Wen Yuan1,2,3
  • Meng-Qi Zhao2,3
  • Xiao-Bai Pang1,2,3
  • Jian Li1,4,5,2,3,6*corresponding author
  • Wei-Ping Wen1,5,2,3,7*corresponding author
  • Nian-Zhen Zheng1,2,3*corresponding author
  1. 1Department of Otorhinolaryngology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
  2. 2Otorhinolaryngology Institute, Sun Yat-sen University, Guangzhou, Guangdong, China
  3. 3Guangzhou Key Laboratory of Otorhinolaryngology, Guangzhou, Guangdong, China
  4. 4Guangxi Hospital Division, the First Affiliated Hospital, Sun Yat-sen University, Nanning, China
  5. 5Department of Allergy, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
  6. 6Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China
  7. 7Department of Otorhinolaryngology, the Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
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Abstract

Spontaneous cerebrospinal fluid (CSF) rhinorrhea is a rare condition, and preoperative identification of the defect location can be challenging. This study aims to summarize the clinical characteristics of spontaneous CSF rhinorrhea and analyze the relationship between ethmoid region defects and missed detection on high-resolution computed tomography (HRCT). We included patients diagnosed with spontaneous CSF rhinorrhea via endoscopic surgery from 2016 to 2024 at the First Affiliated Hospital, Sun Yat-sen University. Retrospective cohort study. Descriptive statistical analysis was conducted to summarize clinical characteristics. The t-test and Fisher's exact test were used for comparison between patients with defects located in the ethmoid region and those without. Multifactorial logistic regression analysis was performed to evaluate the relationship between ethmoid region defects and HRCT missed detection. A total of 49 patients were included in the study, comprising 20 males (40.82%) and 29 females (59.18%). The average BMI was 25.68 kg/m 2. Common symptoms included clear rhinorrhea (89.80%) and headache (20.41%). Multifactorial logistic regression revealed that patients with ethmoid region defects had a 0.04 times lower likelihood of HRCT detection (OR 0.06, 95% CI 0.00–0.40) compared to those with defects located elsewhere. Ethmoid region is the most common site of spontaneous CSF rhinorrhea. Pre-operative detection of rhinorrhea defects using HRCT, the most commonly used imaging method in clinical practice, is challenging. Endoscope exploration is necessary for patients who had suspicious symptoms.

Keywords

Introduction

Spontaneous cerebrospinal fluid (CSF) leaks occur with an incidence of approximately 5 per 10,000 individuals, with nearly 40% of cases being non-traumatic (1). Among these, spontaneous CSF rhinorrhea is the predominant form and is frequently associated with idiopathic intracranial hypertension (IIH). This condition is characterized by a non-negligible recurrence rate (2, 3). As the prevalence of obesity rises, spontaneous CSF rhinorrhea has gained increasing attention within both rhinology and neurosurgery (4). β2-transferrin testing is widely used in clinical practice for qualitative diagnosis of spontaneous CSF rhinorrhea, with a reported sensitivity ranging from 87% to 100% and specificity from 71% to 100% (5).

Accurate localization of the defect is also crucial for the diagnosis and management of spontaneous CSF rhinorrhea (6, 7). The ethmoid roof and cribriform plate are the most common sites of defect, followed by the sphenoid lateral recess and sphenoid roof, and the posterior wall of the frontal sinus was the least affected (8). High-resolution CT (HRCT) is a simple and essential imaging modality for diagnosis, while endoscopy can provide preliminary assessment based on the direction of fluid drainage. However, as the most widely used imaging technique, HRCT exhibits a sensitivity range of 58.8%–100% and specificity between 57% and 100%. Despite its widespread use, HRCT has limitations, particularly in cases with multiple defects (6).

MRI is also utilized in clinical practice, with 3D MRI and heavily weighted T2W MRI significantly improving defect detection. However, the utility of these techniques is limited by the hardware capabilities of medical institutions (9). CT or MRI cisternography, while effective for defect localization, are more invasive, less sensitive, and associated with potential complications (1). Intrathecal fluorescein administration is an intraoperative method for CSF rhinorrhea defect localization. Its sensitivity increased with increasing fluorescein concentration (73.8%–92.9%). Nevertheless, meta-analysis indicated that 60% of patients who underwent this procedure would experience at least one of the measured complications (10).

Despite the availability of various diagnostic methods, some patients still present with unidentified defects before surgery, requiring surgical exploration (11). The cribriform plate and ethmoid roof, being the most fragile parts of the anterior skull base, are often excessively pneumatized and contain numerous natural channels. This anatomical complexity can make defect recognition via imaging, particularly HRCT, challenging (11). In this article, we aim to summarize the clinical characteristics of spontaneous CSF rhinorrhea and investigate whether defects in the ethmoid skull base pose a particular challenge for HRCT detection, suggesting the need for further imaging investigation and possibly surgical exploration.

Methods

Patient inclusion

This retrospective study included patients diagnosed with spontaneous CSF rhinorrhea who were admitted to the otolaryngology department of the First Affiliated Hospital, Sun Yat-sen University, for CSF rhinorrhea repair surgery from January 1, 2016, to December 31, 2024. The inclusion criteria for spontaneous CSF rhinorrhea were: Surgical confirmation was necessary to validate the diagnosis. Patients with a confirmed etiology such as trauma or tumors were excluded from the study.

  • Clear rhinorrhea with a glucose concentration greater than 1.7 mmol/L.
  • HRCT indicating a suspected skull base bone defect.
  • Nasal endoscopy showing clear rhinorrhea from the middle meatus or olfactory cleft.
  • In the absence of the above features, a medical history of clear rhinorrhea (differentiated from allergic rhinitis), meningitis, or aspiration pneumonia was required for empirical diagnosis.

Clinical and imaging data collection and subgroup analysis

Demographic data, clinical symptoms, signs, and endoscopic findings were collected from the medical record system. Two radiologists with over 10 years of experience reviewed the preoperative CT and MR images of these patients. The radiologists confirmed the CSF rhinorrhea-related imaging findings and the location of the skull base defects. The CSF rhinorrhea repair surgeries were performed by experienced rhinologists (12), and the final defect localization was confirmed through surgical records.

To assess the diagnostic performance of HRCT, MRI, and their combination for detecting ethmoid region CSF rhinorrhea, a subgroup comparative analysis was conducted. Patients with defects located at the ethmoid roof and cribriform plate were classified as having ethmoid region CSF rhinorrhea. Patients with defects in the posterior wall of the frontal sinus, sphenoid roof, or sphenoid lateral recess were classified as not having ethmoid region CSF rhinorrhea.

Statistical analysis

Statistical analysis was conducted using R version 4.5.1 (2025-06-13 UCRT). For the description of clinical characteristics and subgroup comparisons, continuous variables were expressed as means (SD), and t-tests were used for differential analysis. Categorical variables were presented as frequencies, with Fisher's exact test used for comparison. Logistic regression was applied to assess risk factors for categorical dependent variables.

Results

According to the inclusion criteria, a total of 49 patients were included in our study, consisting of 20 males (40.82%) and 29 females (59.18%). The average BMI was 25.68 kg/m2, which qualified as overweight. Most of the patients (91.84%) had a history of CSF rhinorrhea-related symptoms lasting more than one month. The most common symptoms were clear rhinorrhea (89.80%) and headache (20.41%), while symptoms such as nasal congestion, anosmia, and central nervous system infections were relatively rare.

To evaluate the efficacy of different diagnostic methods, we calculated the detection rates of CSF rhinorrhea using endoscopy, CT, and MRI. The detection rates were 63.41% (CT), 68.29% (MRI), and 77.14% (endoscopy), respectively. However, all methods had limitations in CSF rhinorrhea detection and defect localization. Image examination revealed 19 patients (38.78%) with meningoencephalocele and 8 patients with empty sella (Table 1).

Table 1. Clinical characteristics of spontaneous CSF rhinorrhea patients.

GroupP value
Clinical characteristicsTotal (n = 49)Location in ethmoid (n = 32)Location not in ethmoid (n = 17)
Gender0.9632
Male20 (40.82%)12 (37.50%)8 (47.06%)
Female29 (59.18%)20 (62.50%)9 (52.94%)
Age40.36 ± 18.38 (yrs)39.65 ± 19.34 (yrs)41.71 ± 16.91 (yrs)0.7131
Height1.55 ± 0.21 (m)1.56 ± 0.20 (m)1.53 ± 0.23 (m)0.7876
Weight63.48 ± 19.50 (kg)63.96 ± 20.41 (kg)64.78 ± 22.57 (kg)0.8472
BMI25.68 ± 4.74 (kg/m2)25.82 ± 4.70 (kg/m2)25.42 ± 4.97 (kg/m2)0.8021
Duration0.9344
<1m4 (8.16%)1 (3.13%)3 (17.65%)
1–3m10 (20.41%)8 (25.00%)2 (11.76%)
3–6m12 (24.49%)7 (21.88%)5 (29.41%)
6m−1y10 (20.41%)7 (21.88%)3 (17.65%)
>1y13 (26.53%)9 (28.13%)4 (23.53%)
Symptom
Headache10 (20.41%)5 (15.63%)5 (28.41%)0.0908
Congestion5 (10.20%)4 (12.50%)1 (5.88%)0.0139
Anosmia0 (0.0%)0 (0.00%)0 (0.00%)
Infection2 (4.08%)1 (3.13%)1 (5.88%)0.0022
Rhinorrhea44 (89.80%)28 (87.50%)16 (94.12%)0.5360
Meningoencephalocele19 (38.78%)12 (37.50%)7 (41.18%)0.5670
Rhinorrhea side(n = 44)(n = 28)(n = 16)0.0425
Unilateral43 (97.73%)28 (100.00%)15 (93.75%)
Bilateral1 (2.27%)0 (0.00%)1 (6.25%)
CT rhinorrhea26 (63.41%) (n = 41)12 (48.00%) (n = 25)14 (87.50%) (n = 16)0.0179
Empty sella8 (19.51%) (n = 41)5 (20%) (n = 25)3 (18.75%) (n = 16)0.0731
MR rhinorrhea28 (68.29%) (n = 41)16 (64.00%) (n = 25)12 (75.00%) (n = 16)0.4624
Endoscope rhinorrhea27 (77.14%) (n = 35)18 (78.26%) (n = 23)9 (75.00%) (n = 12)0.8275
Defect diameter0.75 ± 0.56 (cm) (n = 23)0.67 ± 0.58 (cm) (n = 17)0.94 ± 0.52 (cm) (n = 6)0.2925

To analyze the correlation between defect location in the ethmoid region and HRCT findings, we divided the patients into two groups: one with defects confirmed to be located in the ethmoid region, and the other with defects outside this region. Patients with defects in the ethmoid region had lower rates of headache (5 (15.63%) vs. 5 (28.41%)) and a higher incidence of empty sella (5 (20%) vs. 3 (18.75%)). These patients were also more difficult to detect with HRCT (12 (48%) vs. 14 (87.50%)).

Further, multivariate logistic regression analysis showed that, after adjusting for confounding factors such as headache and empty sella, patients with defects located in the ethmoid region had 0.04 times the risk of being detected by HRCT (OR = 0.06, 95% CI 0.00–0.40) (Table 2).

Table 2. Multiple logistic regression analysis of influencing factor for CSF rhinorrhea ethmoid region location.

VariablesOR (95% CI)P valueRegression coefficient
CT rhinorrhea0.06 (0.00–0.40)0.0146−2.793
Headache0.09 (0.00–0.76)0.0535−2.388
Empty sella0.65 (0.09–4.45)0.6490−0.437

A typical case is presented below. This patient was a 48-year-old woman who was admitted with a headache lasting over one month. She also reported postnasal drip with intracranial pressure of 82 mm H₂O. After excluding trauma, intracranial tumors, cerebrovascular diseases, and nasal diseases, the patient was initially diagnosed with spontaneous CSF rhinorrhea. However, both HRCT and heavily weighted T2W MRI failed to provide positive indications of CSF rhinorrhea. Endoscopic surgery was performed for diagnostic confirmation and defect repair. During ethmoid sinus contouring, a slit-like defect was found on the ethmoid roof of the anterior ethmoid. After repairing the defect with middle meatus flap, the patient experienced significant improvement in headache and postnasal drip (Figure 1).

A confirmed ethmoid CSF leak not identified on HRCT **(A)** or T2W MRI **(B)** endoscopy **(C)** located the defect anterior to the anterior ethmoid artery (arrow).
Figure 1. A confirmed ethmoid CSF leak not identified on HRCT (A) or T2W MRI (B) endoscopy (C) located the defect anterior to the anterior ethmoid artery (arrow).

Discussion

In this study, we reviewed the clinical data of spontaneous CSF rhinorrhea patients at our hospital from 2016 to 2024. Consistent with existing consensus, obese women comprised the majority of these patients. The ethmoid region was found to be the most common site of CSF rhinorrhea (65.3%), as previously reported. Among the patients with ethmoid region CSF rhinorrhea, we observed a lower incidence of headache, which is a typical symptom of idiopathic intracranial hypertension (IIH), and it was more challenging to detect the skull base defect using HRCT.

The relationship between spontaneous CSF rhinorrhea and IIH had been widely discussed. IIH was characterized by intracranial hypertension without structural intracranial or CSF abnormalities, typically presenting with headache and papilledema (4, 13). In clinical data from China, 75.8% of spontaneous CSF rhinorrhea patients were found to have elevated intracranial pressure (ICP) (>180 mmHg), although only a few were diagnosed with IIH (2). Another cohort study conducted in Spain reported a mean ICP of 33.0 cm H2O (range: 20–55 cm H2O), which was also above the normal range (14). Chronic intracranial hypertension can gradually cause bone erosion, leading to CSF leaks and meningoencephalocele at weak areas, such as the cribriform plate, ethmoid roof, and sphenoid lateral recess (14). The natural channels in the cribriform plate, excessive pneumatization of the ethmoid roof, and height differences between these regions contribute to this weakness (15).

We hypothesized that, unlike leakage in the sphenoid lateral recess, which usually had a distinct fistula easily detected by HRCT, the presence of natural channels and the junction between the cribriform plate and ethmoid roof creates favorable conditions for CSF leak formation, leading to difficulties in defect identification. Our data indicated that ethmoid region leakage was 2.8 times harder to detect by HRCT, supporting our hypothesis. This finding suggests that the ethmoid region should be considered when spontaneous CSF rhinorrhea is suspected, even in the absence of clear imaging indications.

Imaging techniques have improved significantly over the past two decades. High-resolution MRI techniques, such as fluid-attenuated inversion recovery (MRI-FLAIR) and constructive interference steady state (CISS), help differentiate between CSF and inflammation/edema (1). Intrathecal CSF cisternography has proven to be an important adjunct for detecting CSF leaks. Various types of cisternography, including CT cisternography, MR cisternography, and radionuclide cisternography, have been reported with sensitivities of 37.5–73.2%, 56–95.65%, and 76%, respectively (6). Due to their varying sensitivity, invasiveness, radiation exposure, and potential complications, CSF cisternography is limited in clinical use (6, 7). For non-invasive alternatives, heavily weighted T2W and 3D gradient sequence MRI have been introduced with sensitivities ranging from 75% to 100% (16). A combined imaging approach, such as CT and MRI, can improve the detection efficacy of CSF rhinorrhea, with sensitivities ranging from 89.74% to 95%, making it a practical and cost-effective approach (6). In our study, 36 patients (79%) were pre-operatively evaluated using combined imaging methods. However, conflicting results between CT and MRI often created confusion for surgeons.

Our study has several limitations. First, ICP was not measured in most patients, so we could not confirm whether they had elevated ICP. Second, we did not distinguish between children and adults in this cohort, which may have influenced the results due to congenital factors. Lastly, the small sample size and retrospective design limit the generalizability and strength of our findings.

In conclusion, our study showed that spontaneous CSF rhinorrhea was commonly observed in overweight, middle-aged women, with symptoms of rhinorrhea and headache. The ethmoid region was the most frequent site of CSF rhinorrhea and was more difficult to detect using HRCT. Endoscopic exploration was essential for patients with suspicious symptoms, even when imaging results were inconclusive.

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Footnotes

Edited by: Eleonora M.C. Trecca, University of Foggia, Italy

Reviewed by: Giulio Bonomo, IRCCS Carlo Besta Neurological Institute Foundation, Italy

Stoyan Markov, Plovdiv Medical University, Bulgaria

Statements

Conflict of interest

The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Funding

The author(s) declared that financial support was received for this work and/or its publication. This work was supported by the National Natural Science Foundation of China (NSFC) (Grant Nos. 82020108009 and 82171766), the Guangdong Natural Science Foundation of China (Grant Nos. 2023B1111040004 and 2022A1515010506), the Key Clinical Technique of Guangzhou (Grant No. 2023P-ZD06), the Guangzhou Science and Technology Project of China (Grant Nos. 2025B01J3002 and 2024A04J10019), the Guangxi Science and Technology Major Program (Grant No. GuikeAA24206008), the Guangxi Key Research and Development Program (Grant No. GuikeAB24010081), the Guangxi Medical and Health Appropriate Technology Development and Promotion Application Project (Grant No. S2024116), the Fundamental Research Funds for the Central Universities, Sun Yat-sen University (Grant No. 23ptpy107), and the National Science and Technology Major Project on Prevention and Control of Emerging and Major Infectious Diseases (Grant No. 2025ZD01903901).

Data availability

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

Ethics approval

The studies involving humans were approved by the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.

Author contributions

J-WZ: Investigation, Writing – original draft, Conceptualization, Data curation, Methodology, Formal analysis. X-YZ: Investigation, Conceptualization, Data curation, Formal analysis, Writing – original draft, Methodology. Y-WG: Methodology, Data curation, Investigation, Writing – original draft, Formal analysis, Conceptualization. J-WY: Data curation, Methodology, Writing – original draft, Investigation. M-QZ: Methodology, Investigation, Writing – original draft. X-BP: Investigation, Methodology, Writing – original draft. JL: Resources, Funding acquisition, Writing – review & editing, Writing – original draft, Supervision, Project administration, Conceptualization. WW: Formal analysis, Project administration, Methodology, Writing – original draft, Supervision, Funding acquisition, Investigation, Data curation, Validation, Conceptualization, Resources. N-ZZ: Data curation, Resources, Investigation, Validation, Conceptualization, Project administration, Visualization, Writing – review & editing, Methodology, Supervision, Writing – original draft, Formal analysis, Software, Funding acquisition.

Acknowledgements

We would like to express our sincere gratitude to the Department of Otorhinolaryngology, The First Affiliated Hospital of Sun Yat-sen University, for its generous support in providing the data required for this article.

References

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Citation

Zhou, J., et al. (2026). Can negative HRCT locate ethmoid CSF leaks? A retrospective analysis. Frontiers in Allergy, Volume 7. https://doi.org/
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7 - 2026

Copyright

© 2026 Zhou, Zhang, Gong, Yuan, Zhao, Pang, Li, Wen and Zheng.

License: https://creativecommons.org/licenses/by/4.0/

*Correspondence: Jian Li; Wei-Ping Wen; Nian-Zhen Zheng

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