Epilepsy surgery in pediatric patients with complex COL4A1/2-associated epilepsy
Jan P Nieke1, Ingrid Koerber-Rosso2, Lena-Luise Becker3,4,5,6,7
1Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany.
Summary
Epilepsy surgery offers a safe treatment for COL4A1/2-related epilepsy. While curative for unilateral cases, bilateral cases benefit from seizure mitigation and developmental support, improving outcomes.
Area of Science:
- Neuroscience
- Genetics
- Neurosurgery
Background:
- Pathogenic variants in COL4A1/2 genes disrupt vascular basement membrane integrity, leading to brain lesions and malformations of cortical development (MCD).
- These vascular disruptions can cause drug-resistant focal epilepsy, particularly in patients with widespread or bilateral MRI abnormalities, often deeming them ineligible for curative surgery.
- A refined surgical strategy is needed to focus on seizure mitigation and functional preservation in these complex cases.
Purpose of the Study:
- To evaluate the feasibility and safety of epilepsy surgery in patients with COL4A1/2-associated epilepsy.
- To assess surgical outcomes, including seizure control and neurodevelopmental improvement, in relation to lesion laterality (unilateral vs. bilateral).
- To explore the role of multimodal imaging, such as FDG-PET, in surgical planning for these patients.
Main Methods:
- Retrospective analysis of six patients (3 COL4A1, 3 COL4A2) from three German epilepsy centers.
- Evaluation of presurgical diagnostics (MRI, PET), surgical techniques (hemispherotomy, posterior quadrant disconnection/resection), histopathology, and patient outcomes.
- Contextualization of findings with a review of 11 previously published cases.
Main Results:
- All patients presented with daily seizures and developmental delay pre-surgery.
- Seizure freedom (ILAE 1) was achieved in 33% of patients, exclusively those with unilateral lesions; patients with bilateral lesions remained at ILAE 4.
- Despite persistent seizures in bilateral cases, 83% showed postoperative developmental improvement. Histopathology suggested secondary cortical malformations drive epileptogenicity. No complications were observed.
Conclusions:
- Epilepsy surgery is a feasible and safe option for COL4A1/2-associated epilepsy, offering curative potential for unilateral lesions.
- A "non-curative" surgical approach focusing on seizure mitigation and neurodevelopmental protection can benefit patients with bilateral lesions.
- Multimodal imaging, particularly FDG-PET, aids in identifying epileptogenic zones within widespread damage, guiding surgical planning.
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