Chirurgiczne leczenie epilepsji u dzieci z zespołem COL4A1/2 - złożone przypadki
Epilepsy surgery in pediatric patients with complex COL4A1/2-associated epilepsy
W skrócie
Badanie dotyczy dzieci z rzadką chorobą genetyczną (COL4A1/2), która uszkadza naczynia krwionośne w mózgu i powoduje trudną do leczenia epilepsję. Lekarze zbadali 6 dzieci poddanych operacji mózgu i stwierdzili, że zabiegi chirurgiczne są bezpieczne i mogą pomóc - u dzieci z uszkodzeniami tylko jednej półkuli mózgu udało się całkowicie wyeliminować napady, a u pozostałych poprawiło się rozwój psychiczny i zmniejszyła się liczba napadów, mimo że całkowite wyleczenie nie było możliwe.
Oryginalny abstract (angielski)
OBJECTIVE: Pathogenic variants in COL4A1/2 compromise vascular basement membrane integrity, causing intrauterine hemorrhage and infarction leading to extensive structural brain lesions. Vascular disruptions during critical windows of neuronal migration can result in malformations of cortical development (MCD), which may drive epileptogenicity. While surgery is established for drug-resistant focal epilepsy, COL4A1/2 patients with widespread or bilateral MRI abnormalities are frequently deemed ineligible. In selected patients, this necessitates a refined surgical rationale, shifting from strictly curative goals to "non-curative" strategies focused on seizure mitigation and functional preservation. METHODS: This retrospective multicenter study analyzed six previously unpublished patients (3 COL4A1, 3 COL4A2) from three German epilepsy centers. We evaluated presurgical diagnostics (MRI, PET), surgical techniques, histopathology, and outcomes. Results were contextualized with a review of 11 previously published cases. RESULTS: All patients experienced daily seizures and developmental delay prior surgery. MRI revealed bilateral abnormalities in 4/6 patients (e.g., ventriculomegaly, white matter lesions). Surgical procedures included hemispherotomy (n = 4) and posterior quadrant disconnection/resection (n = 2). Mean follow-up was 5 years 11 months (range 2 years 10 months-8 years 9 months). Seizure freedom (ILAE 1) was achieved in 2/6 patients (33%), both of whom had unilateral lesions. While patients with bilateral lesions remained at ILAE 4, 83% showed postoperative developmental improvement. Histopathology confirmed cortical malformations in three patients (FCD IIId, mMCD II, GW-matter blurring), supporting the hypothesis that secondary cortical malformations, rather than macroscopic lesions, drive epileptogenicity. No surgical or neurovascular complications were observed. SIGNIFICANCE: Epilepsy surgery is a feasible and safe treatment option for COL4A1/2-associated epilepsy. While curative in patients with unilateral lesions, bilateral cases can benefit from a "non-curative" approach focused on seizure mitigation and neurodevelopmental protection. Multimodal imaging, specifically FDG-PET, can be helpful in identifying highly epileptogenic cortical areas within widespread structural damage and serve as a basis for surgical planning.