OP17 – 2537: Epilepsy, clinical presentation and MRI features in patients with COL4A1 mutations

Objective COL4A1 mutations disrupt the integrity of basement membranes and therefore predispose to a broad spectrum of disorders affecting multiple organ systems, but most notably causing cerebral small vessel disease. There is little data on epilepsy in these patients. The aim of our study was to describe characteristics of epilepsy in patients with COL4A1-mutations including therapeutical aspects, to establish diagnostic criteria on the basis of typical MRI findings and to evaluate co-morbidities. Patients and methods Data was collected retrospectively by attending physicians via standardized questionnaires. MRI images were reviewed by one experienced pediatric radiologist in our centre (PW). Results All 6 patients had history of pre- or perinatal stroke or cerebral hemorrhage and later showed impairment of cognitive functions and motor development. Epilepsy in all patients manifested within the first year of life (3–10 months, mean: 6 months). Multiple antiepileptic drugs were administered (4–11; mean: 6.3); among those, valproic acid (4/6) and vigabatrin (4/6) proved effective whereas oxcarbazepine had aggravating effects in 2/6 patients. All patients showed co-morbidities such as ophthalmological disorders (6/6), microcephaly (6/6), and elevation of plasma creatine kinase levels (4/6). We identified generalized leukomalacia in one or both cerebral hemispheres, focal cystlike white matter defects and focal or multifocal (susceptibility-related) residual signs of hemorrhage/hemosiderin deposition not related to arterial infarction as concordant MRI findings in all 6 patients. Conclusion COL4A1 mutations should be considered as differential diagnosis in children with history of pre-/perinatal stroke or cerebral hemorrhage, impairment of cognitive and motor development and epilepsy. Despite the heterogeneity of the clinical phenotype, typical MRI findings and co-morbidities can lead to the correct diagnosis. Epilepsy in our patients with COL4A1-mutations manifested in the first year of life; in the small collective of our ongoing study, valproic acid and vigabatrin were the most effective antiepileptic drugs. COL4A1 mutations disrupt the integrity of basement membranes and therefore predispose to a broad spectrum of disorders affecting multiple organ systems, but most notably causing cerebral small vessel disease. There is little data on epilepsy in these patients. The aim of our study was to describe characteristics of epilepsy in patients with COL4A1-mutations including therapeutical aspects, to establish diagnostic criteria on the basis of typical MRI findings and to evaluate co-morbidities. Data was collected retrospectively by attending physicians via standardized questionnaires. MRI images were reviewed by one experienced pediatric radiologist in our centre (PW). All 6 patients had history of pre- or perinatal stroke or cerebral hemorrhage and later showed impairment of cognitive functions and motor development. Epilepsy in all patients manifested within the first year of life (3–10 months, mean: 6 months). Multiple antiepileptic drugs were administered (4–11; mean: 6.3); among those, valproic acid (4/6) and vigabatrin (4/6) proved effective whereas oxcarbazepine had aggravating effects in 2/6 patients. All patients showed co-morbidities such as ophthalmological disorders (6/6), microcephaly (6/6), and elevation of plasma creatine kinase levels (4/6). We identified generalized leukomalacia in one or both cerebral hemispheres, focal cystlike white matter defects and focal or multifocal (susceptibility-related) residual signs of hemorrhage/hemosiderin deposition not related to arterial infarction as concordant MRI findings in all 6 patients. COL4A1 mutations should be considered as differential diagnosis in children with history of pre-/perinatal stroke or cerebral hemorrhage, impairment of cognitive and motor development and epilepsy. Despite the heterogeneity of the clinical phenotype, typical MRI findings and co-morbidities can lead to the correct diagnosis. Epilepsy in our patients with COL4A1-mutations manifested in the first year of life; in the small collective of our ongoing study, valproic acid and vigabatrin were the most effective antiepileptic drugs.