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Year : 2018  |  Volume : 7  |  Issue : 4  |  Page : 146-149

Preoperative topical intranasal fluorescein in diagnosis of cerebrospinal fluid rhinorrhea

1 Department of Otolaryngology, Hakim Digestive Disease Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
2 Department of Neurosurgery, Hakim Digestive Disease Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
3 Department of Internal Medicine; Poursina Hakim, Hakim Digestive Disease Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

Date of Web Publication31-May-2019

Correspondence Address:
Dr. Zhale Amini
ENT Department, Azzahra Hospital, Isfahan
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/atr.atr_87_18

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Background and Objectives: The preoperative diagnosis of cerebrospinal fluid (CSF) leak site is necessary for the management of CSF rhinorrhea. At present, intrathecal fluorescein is a common approach for it; however, regarding drawbacks, its value is limited. This study aimed at examining the effects of topical intranasal fluorescein (TINF) on the preoperative diagnosis of CSF rhinorrhea and intraoperative localization of CSF fistula. Patients and Methods: In this cross-sectional study, 32 consecutive patients with CSF rhinorrhea were recruited. Topical intranasal 10% fluorescein was placed in common sites of leakage, the middle turbinate meatus, the roof of the ethmoid plate, and sphenoethmoidal recesses. Change of the color of fluorescein indicated the presence of CSF, and thus, the site of the fistula could be outlined. The accuracy rates of diagnosis of leak site identified by TINF were compared with those by available imaging modalities, CSF analysis, intraoperative findings, and follow-up. Results: The cause of the leak was traumatic in 22 patients and nontraumatic in 10 patients. Preoperative accuracy rate of the location of CSF fistula was estimated 58.3% by available imaging study. The preoperative diagnosis rate of CSF rhinorrhea and the CSF fistula site localization rate by TINF were both 100%. No recurrence was found during the follow-up for 2–12 months. No complication had been reported. Conclusions: Preoperative TINF is an easy, quick, sensitive, safe, and accurate tool in localization of the site of the CSF fistulas and can be considered as a viable noninvasive alternative to the intrathecal fluorescein technique for preoperative diagnosis of CSF rhinorrhea.

Keywords: Cerebrospinal fluid, endoscope, fluorescein, intrathecal, rhinorrhea, skull base, topical

How to cite this article:
Hashemi Jazi SM, Amini Z, Saboori M, Raisi M. Preoperative topical intranasal fluorescein in diagnosis of cerebrospinal fluid rhinorrhea. Arch Trauma Res 2018;7:146-9

How to cite this URL:
Hashemi Jazi SM, Amini Z, Saboori M, Raisi M. Preoperative topical intranasal fluorescein in diagnosis of cerebrospinal fluid rhinorrhea. Arch Trauma Res [serial online] 2018 [cited 2020 May 27];7:146-9. Available from: http://www.archtrauma.com/text.asp?2018/7/4/146/259509

  Introduction Top

Cerebrospinal fluid (CSF) rhinorrhea was described as the leakage of CSF into the nasal cavity.[1] The most important causes of CSF rhinorrhea are traumatic including crash and iatrogenic injuries and nontraumatic including congenital, neoplastic, and spontaneous.[2],[3]

For the management of CSF rhinorrhea, there are some guiding principles including leak confirmation, precise site localization, and sufficient closure.[4]

All patients with gross CSF leakage were imaged to find the location of the fistula.[5],[6],[7] Regarding limited sensitivity of available imaging modalities, injection of fluorescein into a thecal space is the most common tool to precisely determine the localization of the leak site. In this technique, the site of CSF leakage is established by detecting the green color of intrathecal fluorescein (ITF) in the nasal cavity.[8],[9] Some investigations have explained complications and disadvantages of this method,[10],[11] while some studies demonstrated the safety of intrathecal injection of diluted low-dose fluorescein.[12],[13]

Some authors have recommended the topical application of fluorescein intranasally to localize the site of CSF rhinorrhea. While safety considerations have limited ITF use, the intranasal approach may be a good alternate to decrease the ITF side effects.[14],[15] There are only a few published articles in the current English literature regarding topical intranasal fluorescein (TINF) for the diagnosis of CSF rhinorrhea, though interest to use topical fluorescein is increasing nowadays. The present study was conducted to focus on the utility of TINF in the preoperative localization of the site of CSF fistulas and also to examine the results of TINF in identifying and closing skull base defects.

  Patients and Methods Top

This case series included 32 patients (11 women and 21 men) with suspected CSF rhinorrhea. All patients were admitted with clear sweet or salty nasal discharge. All patients were recruited at the Kashani Hospital, Isfahan, Iran, from September 2014 to February 2016. Furthermore, all the patients were evaluated by detailed history taking, neurosurgical, and ear, nose, and throat examination. We used a combination of the available imaging techniques for our cases including axial and coronal computed tomography (CT) scan and/or magnetic resonance imaging (MRI). CT cisternography did not available at that time. The suspected nasal discharge was evaluated for glucose and protein content, a simple test to check whether the rhinorrhea fluid was CSF or not.

In the present study, the patients were divided into two main groups based on the etiology of the leak: (a) nontraumatic and (b) posttraumatic CSF leaks. In Group A, these patients likely have unrecognized raises in intracranial pressure such as benign intracranial hypertension and other neurologic causes. Group B consisted of patients with posttraumatic CSF leaks.


The patients were placed in the supine position, and 1–3 milliliters of CSF was withdrawn and sent to a laboratory. Local anesthesia of the nasal cavity mucous membrane was done with 1% lidocaine and 0.25% phenylephrine, and then, cotton pads soaked with fluorescein were placed. Fluorescein is available in 10% solution in a 5-mL box for ophthalmology usages. We did not dilute it. Three fluorescein-soaked cotton pads were placed in the middle turbinate meatus, the roof of the ethmoid plate, and sphenoethmoidal recesses, respectively. Thereafter, endoscopic examination of the nasal cavity was repeated again carefully by Valsalva maneuver and/or leaning forward. Zero-degree lens rigid 4-mm endoscopes (Chammed, XVS3, China) were used to explore the nasal cavity. As previous studies, a change in the color of the fluorescein from brown to green fluorescence was considered as the presence of CSF, and then, the site of the leak could be outlined.[14]

The accuracy rate of leak site identification was evaluated by comparing with glucose and protein analysis, imaging, intraoperative findings, and follow-up. β2-transferrin assay was not performed because it was not accessible routinely in our region.

Endoscopic repair was carried out in standard fashion.[16] The patients were followed for at least 2-month periods. None of the other individuals needed to endoscopic intervention during the period of follow-up.

The outcome was determined through hospital evidence or telephone with standard questions used to evaluate the recurrence or side effects, such as meningitis, seizures, and chronic sinusitis. Moreover, a history of postnasal discharges, salt tasting, and CSF leakage after strain was obtained.

Informed consent was obtained from all patients, and the protocol of the study was approved by the Ethics Committee at Vice-Chancellor of Research of Isfahan University of Medical Sciences. All procedures and examinations were conducted by the authors of this paper as a collaborative effort of the departments of neurosurgery and otolaryngology.

  Results Top

Patients' characteristics

Thirty-two consecutive patients with suspected rhinorrhea were included in this study. The mean age of the patients was 28.6 years (age range, 7–63 years). Of these patients, 11 cases were female (34.3%) and the remainder were male. Unilateral watery rhinorrhea was the most common preoperative symptom and was found in all cases. Headache, smell disorders (anosmia and hyposmia), and vomiting were also reported [Table 1]. A single episode of meningitis was recorded preoperatively in two patients, but no mortality occurred. In this series, no significant difference was found in rhinorrhea and smell disorders between posttraumatic and non-traumatic groups [Table 1].
Table 1: Patients' demographic characteristics

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In the present study, the preoperative accuracy rate of localization of CSF fistula was estimated 58.3% (13 out of 24) using available imaging studies including coronal and axial spiral CT scan or MRI. TINF was implicated to all patients in this series according to our protocol. The majority of the leaks (22 cases) occurred at the level of the cribriform plate, and only two defects were located in the sphenoid sinus. No case had more than one defect.

In 8 patients (25%), no fistula tract could be identified using multiple modalities [Table 2]. In all of these 8 cases, evaluation including examination, available imaging mostly CT, and follow-up could not identify the site of the CSF fistula.
Table 2: Location of cerebrospinal fluid leakage base on etiology

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Suspicious specimens were sent to a laboratory to assess for glucose and protein, and all samples were reported positive for glucose and protein. Topical intranasal application of fluorescein was positive in all these individuals too.

Endoscopic closure was done for six patients who failed to respond conservative treatment including two revision surgeries who failed after previous repairs. Nine other individuals were nominated for surgery but left our center and refused to cooperate for various reasons. In follow-up, six of the patients underwent surgery in other centers and were excluded from the follow-up. In all six patients who were surgically treated, intraoperative ITF verified the site of leakage, which had been reported by TINF previously.

The authors alerted participants for probable complications such as topical hypersensitivity, vomiting, and sinusitis, but we did not receive related reports in follow-up. No patient developed chronic sinusitis. No major neurological symptoms were described by any patients, but minor symptoms such as dizziness or occasional headaches without neck stiffness or fever were reported by eight patients (25%).

In patients who underwent surgery, the efficacy of closure was complete. There were no persistent leaks after surgery, and no late recurrence was diagnosed during follow-up. One of the patients had transient lower extremity weakness after surgery which may be caused by lumbar drain placement, while no complication was seen in other individuals.

In the present study, the average follow-up for patients who remained in the center was 6 months (range, 2–12 months), but nine patients who left the center were lost during follow-up.

  Discussion Top

CSF rhinorrhea can occur spontaneously, but trauma and iatrogenic injuries are the most common etiologies of it.[17] Regardless of etiology, patients with CSF leakage may have silent symptoms. They may suffer from generally unilateral sweet or salty taste rhinorrhea, nasal obstruction, or meningitis.[6],[18] Chronic CSF leakages may cause a low-pressure headache.[19] Unilateral clear rhinorrhea is the most common presentation, although bilateral CSF rhinorrhea has reported.[20] These findings are in accordance with the results of the present study.

Precise pre- and intraoperative localization of the site of CSF leakage has proved particularly significant. The inconvenience and complications attributed to ITF[9],[11],[21],[22] have an obligate physician to explore minimally invasive, simple, and convenient processes for localization of CSF fistula.[19],[23] Jones first localized the intraoperative CSF fistula using topical nasal fluorescein in three patients.[15] Saafan acknowledged later that TINF can be considered as a viable noninvasive alternative to ITF.[14] In the present study, no major or minor complication regarding TINF was seen. Moreover, Jones and Saafan reported no complication attributed to TINF in their studies.[14],[15] Furthermore, there is no discrepancy between the findings of the current study and those of other studies in this issue.[3],[18]

Although in the present study, Trendelenburg positioning and Valsalva maneuvers have been employed to promote CSF leakage, these maneuvers may be impractical in all traumatic patients, but it may be unnecessary in many cases.

Even though both ITF and TINF may have similar inadequacy if the patient is not actively leaking at the time of study and in tiny cracks and subsequent very small CSF leakage, an active leak may be essential for appropriate diagnosis in both of them. However, in temporary CSF leakage, preoperative imaging techniques may be improved diagnostic accuracy.

The finding of this study was similar to the findings of some other studies that denoted preoperative TINF is as sensitive as glucose and protein in detecting CSF leakage.[9],[18],[24],[25] Adding glucose level to TINF can increase accuracy,[18],[26] but because sometimes catching sufficient and suitable fluid for this analysis may be impossible, TINF can be helpful in this suspicious rhinorrhea. The results of the present study were in line with those of the previous similar studies in case of safety and accuracy.

The present study had a number of limitations that must be acknowledged. At first, this study was an uncontrolled case series and the results would be more convincing if ITF and preoperative TINF were compared in a double-blind, placebo-controlled, clinical trial. This is a good topic for future studies in collaboration of neurosurgery and otolaryngology departments. Second, our study group was heterogeneous in terms of cause, age, gender, and other demographic factors, and this diversity may conceal some differences. Therefore, further generalization of these results should be done with caution. Longer outcome of patients who managed by this approach as well as the long-term safety and efficacy of TINF is warranted to fully evaluate and remain as a question which needs subsequent systematic and perhaps prospective studies.

  Conclusions Top

Preoperative TINF may be a specific and sensitive tool in identifying preoperative CSF leakage and may identify the leak site in many of the cases regardless of etiology and therefore may be a useful and safe adjunct in endoscopic repair of skull base defects. Preoperative TINF may be easier and less expensive than ITF. Fluorescein can be used even as outpatient investigation for preoperative diagnosis of CSF rhinorrhea in the future because it is a simple, quick, relatively inexpensive, safe, and accurate technique.

Financial support and sponsorship

This study was financially supported by Isfahan University of Medical Sciences.

Conflicts of interest

There are no conflicts of interest.

  References Top

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Lindstrom DR, Toohill RJ, Loehrl TA, Smith TL. Management of cerebrospinal fluid rhinorrhea: The Medical College of Wisconsin experience. Laryngoscope 2004;114:969-74.  Back to cited text no. 2
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Jones ME, Reino T, Gnoy A, Guillory S, Wackym P, Lawson W, et al. Identification of intranasal cerebrospinal fluid leaks by topical application with fluorescein dye. Am J Rhinol 2000;14:93-6.  Back to cited text no. 15
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  [Table 1], [Table 2]


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