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

Abstract

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 fulltext 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.

Multimodal diagnosis of cerebrospinal fluid rhinorrhea: State of the art review and emerging concepts

“…Fluorescein changes to a green color upon contact with CSF, and having the patient perform a Valsalva maneuver may lead to confirmation and localization 11 . A systematic review of seven studies found this to have a diagnostic accuracy rate of >96%, 12 though another systematic review astutely pointed out that only three studies before 2021 were utilized as pre‐operative diagnostic tools (as opposed to intraoperative), and all located already confirmed leaks 13 . Nevertheless, patients may not be actively leaking during the time of examination, which may be due to concurrent inflammation or a ball‐valve effect with intracranial contents during periods of low intracranial pressure 4,6,7 …”

“…If done for the purposes of diagnosis, providers may opt for intrathecal fluorescein injection, which dyes CSF green and can be further visualized in the nasal cavity with a blue light filter (Figure 3). 4 Two systematic reviews have been published on the topic in the last few years, with results suggesting a >78% success rate in localization, though this varies with fluorescein dose 39,40 . False negatives can be obtained in patients with lumbar stenosis, insufficient dosing, small defects that ball‐valve with intracranial content, low CSF volume, and adhesions in prior meningitis patients 11 .…”

“…4 Two systematic reviews have been published on the topic in the last few years, with results suggesting a >78% success rate in localization, though this varies with fluorescein dose. 39,40 False negatives can be obtained in patients with lumbar stenosis, insufficient dosing, small defects that ball-valve with intracranial content, low CSF volume, and adhesions in prior meningitis patients. 11 It is important to note, however, that intrathecal fluorescein administration is not FDA approved, and requires informed consent for potential side effects that can be as severe as seizures and lower extremity weakness.…”