Intrathecal Application of a Fluorescent Dye for the Identification of Cerebrospinal Fluid Leaks in Cochlear Malformation
February 29th, 2020
Intrathecally applied fluorescein is used to achieve intraoperative visualization of CSF leaks. This protocol describes a lumbar puncture, the application of 5% fluorescein, and intraoperative visualization using a fully digital microscope.
Cerebrospinal fluid leaks can either be caused by trauma, can pre-exist congenitally, or can appear spontaneously. In cases of CSF leaks, a reliable detection of its origin is needed in order to seal the leaks efficiently, and to prevent complication such as meningitis. With this video, we aim to present a method to identify a temporal basal cerebrospinal fluid leak.
The case of a child with a bilateral temporal bone malformation was chosen in order to demonstrate how the intrathecal application of fluorescein can assist the orientation in anatomical variations or malformations, especially in temporal bone surgery, where a precise work, and also a good knowledge about the anatomical structures, is mandatory. The safety can be increased to a large extent by applying this method. This video protocol was approved by the local Ethics Committee in accordance with the Helsinki declaration.
Informed consent was obtained from all the participants.Protocol. Preparation for surgery. Make sure to obtain audiological testing, high-resolution computer tomography, and MRI of the skull base.
Obtain written informed consent about the off-label use of fluorescein. In a first step in preparation for surgery, perform lumbar puncture and place a lumbar drain for later application of the dye. Use fluorescein sodium with a 10%concentration.
For lumbar application, dilute the fluorescein to a 5%concentration with aqua. Apply 0.1 milliliter of the dilution per each 10 kilograms of body weight, with a maximum of one milliliter intrathecally. Perform the application immediately before surgery in order to achieve intraoperative visualization.
When applying the method in children, the application should be performed in general anesthesia. General anesthesia is performed according to the patient's individual clinical history and risk factors according to the decision of the anesthesiologist. Cover the microscope with a blue light filter to visualize the fluorescein, or use a fully digital microscope.
Use sterile draping to cover the patient.Surgery. For the transmastoid approach, perform mastoidectomy and posterior tympanotomy. Expand the surgery according to the expected origin of the leak.
As a first land mark, expose the dura to the middle cranial fossa. Thin out the posterior canal wall of the outer ear canal. Expose the short incus process in the antrum, and identify the lateral semicircular canal.
As the next surgical step, expose the chorda facial angle, where the chorda tympani leaves the facial nerve. Open the facial recess. Leave the facial nerve with a bony coverage.
Access the middle ear through posterior tympanotomy. The origin of the fluid leak can easily be identified in the stapes footplate. Use fascia from the temporal muscle and absorbable collagen-fibrin sealant patches to seal the CSF leak until no more fluid leaves the footplate.
The stapes superstructure is stabilizing the sealant.Results. In the presented case, minor trauma has led to a CSF leak from the nose in a ten month old child. MRI revealed bilateral temporal bone malformation, with aplasia of the right cochlea and a dilatation of the left cochlea and vestibule, with absent interscalar septum.
Identical to an incomplete partition type I.Brainstem-evoked audiometry was performed and confirmed bilateral deafness. Since high-resolution computer tomography did not reveal the origin of the CSF, fluorescein assisted transmastoidal auto-basal exploration with simultaneous cochlea implantation was indicated. During primary surgery, the trans-mastoidal approach was used to identify the CSF in the stapes footplate, to seal the leak, and to perform cochlear implantation for hearing restoration.
Six months after prior surgery, the child suffered from meningitis caused by mastoiditis. The implant was removed and the electrode array was left as a spacer. Postoperatively, the oral smell detected beta transferrin.
Revision mastoidectomy was performed, showing a dislocated coverage of the leak in the stapes footplate. The stapes was completely removed, and the oval window was sealed using temporal muscle, temporal fascia, and absorbable collagen-fibrin sealant patches. The stapes was investigated under the electron microscope, showing the malformated footplate with perforation.
In order to reduce the pressure onto the leak, lumbar puncture was performed daily. Five days after revision, no more beta transferrin was detected. During cochlear implant revision six months later, the coverage of the oval niche was intact.
The presented case shows that the intrathecal application of fluorescein can be used for the intraoperative identification of auto-basal CSF leaks. It facilitates the orientation in malformations or in a complicated or unknown anatomical variation of the temporal bone. This method has been used in several of our clinical cases, and the results confirm the visibility of safely accessing the origin of the leak.
View the full transcript and gain access to thousands of scientific videos
Overview
This article presents a method for intraoperative visualization of cerebrospinal fluid (CSF) leaks using intrathecal fluorescein application. The protocol includes a lumbar puncture and the use of a fully digital microscope for enhanced visualization during surgery.
Key Study Components
Area of Science
- Neurosurgery
- Cerebrospinal fluid management
- Intraoperative imaging techniques
Background
- CSF leaks can result from trauma, congenital conditions, or occur spontaneously.
- Reliable detection of CSF leak origins is crucial to prevent complications like meningitis.
- Understanding anatomical variations is essential in temporal bone surgery.
- This method aims to improve safety and precision in surgical procedures.
Purpose of Study
- To demonstrate the effectiveness of fluorescein in identifying CSF leaks.
- To provide a protocol for its application in pediatric cases with anatomical malformations.
- To enhance surgical outcomes through improved visualization techniques.
Methods Used
- Intrathecal application of 5% fluorescein.
- Digital microscopy for intraoperative visualization.
- Case study of a child with bilateral temporal bone malformation.
- Ethics approval in accordance with the Helsinki declaration.
Main Results
- Fluorescein application aids in the identification of CSF leaks.
- Improved orientation in complex anatomical variations.
- Increased safety during temporal bone surgeries.
- Demonstrated effectiveness in a clinical case study.
Conclusions
- Intrathecal fluorescein is a valuable tool for CSF leak detection.
- This method enhances surgical precision and safety.
- Further studies may expand its application in various surgical contexts.
Frequently Asked Questions
Executive Industry Relevance
Reliable intraoperative identification of cerebrospinal fluid (CSF) leaks is critical for de-risking surgical interventions in anatomically complex or malformative cases. The use of intrathecal fluorescein enables precise localization of CSF leak origins, supporting confident surgical decision-making and reducing the risk of postoperative complications such as meningitis. This capability is particularly relevant for translational research and device development targeting neurological and otologic disorders.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Enables mechanistic de-risking by directly visualizing CSF leak pathways in disease-relevant anatomical models.
- Supports functional validation of surgical targets in congenital and acquired malformations.
- Facilitates hypothesis-driven exploration of CSF dynamics and leak etiology.
Screening & Assay Development
- Provides a validated intraoperative readout for leak detection, supporting reproducible assessment across cases.
- Standardizes visualization protocols for evaluating surgical interventions and device prototypes.
- Enables quantitative comparison of leak sealing efficacy using fluorescent signal as a dependent variable.
Translational & Preclinical Research
- Aligns with translational biomarker strategies by correlating intraoperative findings with postoperative biochemical markers (e.g., β-transferrin).
- Supports continuity from surgical discovery through preclinical validation of leak repair techniques.
- Reduces translational risk by providing objective intraoperative endpoints for intervention success.
Pipeline & Workflow Integration
This method integrates into the surgical discovery-to-validation continuum, bridging anatomical hypothesis testing with preclinical model evaluation and device development.
- Discovery Biology: Facilitates direct testing of CSF leak hypotheses in anatomically complex systems.
- Screening: Delivers reproducible, quantitative intraoperative visualization for intervention assessment.
- Analytics: Enables measurement of leak localization and sealing outcomes using fluorescence and biochemical markers.
- Translational Research: Connects intraoperative findings to postoperative biomarker validation, supporting risk-adjusted advancement.
- Enterprise Reuse: Establishes a reusable protocol for CSF leak detection across diverse surgical and preclinical models.
Operational & Enterprise Impact
- Scientific Value: Increases predictive confidence in leak localization and repair strategies.
- Operational Value: Standardizes intraoperative visualization and post-surgical assessment workflows.
- Strategic Value: Improves go/no-go decisions for device and intervention development targeting CSF dynamics.
- Portfolio Impact: Enables risk-adjusted prioritization of surgical and device-based solutions for CSF leak management.
Implementation Considerations
- Requires expertise in neurosurgical and otologic anatomy for accurate interpretation of fluorescent signals.
- Demands access to digital microscopy and fluorescence-compatible surgical infrastructure.
- Necessitates cross-team standardization of dye concentration, timing, and visualization protocols.
- Adaptation may be needed for different anatomical sites or patient populations.
- Off-label use and ethical considerations must be addressed in clinical and preclinical settings.
