Fluorescence Guided Focal Cortical Dysplasia Surgery

Overview

Epilepsy is one of the most common neurological disorders, with one of the highest morbidity rates of all diseases. Despite the development of new anticonvulsant drugs, around a third of patients suffer from drug-resistant epilepsy (RPE). The onset of RPE can be lengthy, prolonging the period during which affected patients live with seizures that have a negative impact on their quality of life. Epilepsy surgery can be a curative treatment, and can enable anticonvulsant medication to be discontinued, optimizing quality of life and cognitive development. In addition, as it has been shown that the prolonged duration of epilepsy prior to surgery has an impact on the occurrence of postoperative seizures, early surgery is increasingly being considered. Focal cortical dysplasia (FCD) is the leading cause of focal lesional epilepsy and is generally drug-resistant. Good postoperative seizure results after surgical resection are strongly linked to complete resection of the dysplastic tissue. Consequently, accurate localization and precise delineation of FCD lesions are crucial during surgery. Currently, the extent of surgical resection is based primarily on preoperative examination, as the macroscopic appearance of dysplastic tissue does not differ from normal cortex. The various intraoperative techniques available to improve the quality of excision (neuronavigation, ultrasound, intraoperative MRI and intraoperative guidance by fluorescence microscopy) all have their limitations. In this context, new intraoperative tools are needed to help the neurosurgeon delineate lesions during surgery. Intraoperative fluorescence spectroscopy is used for surgical guidance of gliomas and other brain pathologies, and has demonstrated its ability to characterize pathological tissues. DCFs exhibit metabolic differences that can also be detected by 5-amino-levulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence intraoperatively. Indeed, in some patients who underwent surgery after a diagnosis of glioma, fluorescence was observed even though histological analysis classified the excised tissue as DCF. What's more, glioma and DCF share a common feature: the mitochondria of affected cells are deficient in complex IV. Cytochrome c oxidase (CCO) is largely involved in mitochondrial complex IV, and NAD is a central metabolite involved in redox reactions within cells. Both metabolites (CCO and NAD) can be visualized intraoperatively by optical and fluorescence spectroscopy. FLUOFOCODYS is a prospective, non-comparative, single-center, human drug pilot clinical trial. 5 patients will be included.

Detailed description

Primary objective of FLUOFOCODYS study is to measure the fluorescence of biomarkers of focal epileptic lesions by intraoperative fluorescence spectroscopy.

The secondary objectives are as follows:

1. To compare the measurement of FCD volume between multimodal high-resolution MRI (HRM) and standard MRI. 2. To assess the concordance of FCD measurements between multimodal high-resolution MRI (HRM) and standard MRI. 3. Evaluate the correlation between fluorescence spectroscopy and SpiderMass measurements on the collected tissue sample. 4. Describe any adverse events that occurred after treatment up to the end of study participation.

The hypothesis of this project is that intraoperative fluorescence spectroscopy could robustly measure 5-ALA-induced protoporphyrin IX fluorescence in FCD and could ultimately aid FCD surgery. Thus, to understand intraoperative biomarker fluorescence spectroscopy in DCF, preoperative MRI and postoperative histology are crucial. This will enable MRI-informed intraoperative fluorescence spectroscopy. These comparative measurements will be completed with SpiderMass technology (metabo-lipidomic mass spectrometry). The effectiveness of intraoperative tools could therefore be assessed prior to surgery, which could have an impact on the therapeutic decision to proceed with surgery.

Interventions

• Drug 5-ALA (Gliolan)
  Patients will be given 5-ALA (20 mg per kilogram body weight) before the surgery, between 2 and 4 hours before anaesthesia.

Primary outcome measures

• Concentration of fluorescent compound (in mol/L) during the chirurgical intervention on the extracted tissue sample of FCD [Time frame: Day 0]

Secondary outcome measures (7)

• FCD volume in mm3 on standard MRI [Time frame: 60 days before Day 0 (=surgery)]
• FCD volume in mm3 on High Resolution MM- MRI [Time frame: Day 0 (=surgery)]
• Index kappa concordance of the volume in mm3 of focal cortical dysplasia measured by standard MRI [Time frame: 60 days before day 0]
• Index kappa concordance of the volume in mm3 of focal cortical dysplasia measured by HR MM-MRI [Time frame: Day 0]
• Concentration measured by fluorescence spectroscopy on extracted tissue sample of FCD [Time frame: Day 0]
• Relative concentration of molecular species measured by SpiderMass on extracted tissue sample of FCD [Time frame: Day 0]
• Number of adverse events [Time frame: From the enrollment to day 1]

Eligibility criteria

Inclusion criteria

• Patient with drug resistant epilepsy, related to a type II FCD visible on MRI
• Patient with surgical indication validated by the epileptic multi-disciplinary staff meeting
• First FCD surgery
• Signed written informed consent before any study specific intervention
• Patient affiliated to the national health system or benefiting from it

Exclusion criteria

• Patients weighing over 75kg
• Patients requiring general anaesthesia for MRI at investigator discretion
• Contra indication to MRI : obesity, claustrophobia, metallic object
• Hypersensitivity to the active substance or to porphyrins
• Acute or chronic porphyria
• For woman of childbearing potential: Pregnancy or breastfeeding or patients who is not willing to comply with the contraceptive requirements during the study period
• Inability to follow the procedures of the study
• Simultaneous enrolment to another study which could influence the results of the current study
• Patient under legal protection or deprived of liberty

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Other

Study locations

France · 2 centers

• Hôpital Neurologique Pierre Wertheimer - Groupement Hospitalier Est - Hospices Civils de L — Bron
• Hôpital Femme Mère Enfant - Groupement Hospitalier Est - Hospices Civils de Lyon — Bron

Identifiers

NCT: NCT07657975 · 69HCL24_0906 · 2025-523608-64-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗