Abstracts

Rationale: Solitary extratemporal FCD is the most common brain MRI finding in children with intractable partial epilepsy treated by epilepsy surgery. FCD is sporadic, and most children with FCD have normal exam. TSC is not considered in the differential diagnosis of FCD on the brain MRI, unless dictated by the presence of bilateral cortical tubers, subcortical migrational abnormalities, subependymal nodules, and giant cell astrocytomas. We report 5 children with epilepsy due to a solitary FCD on the brain MRI, who were later diagnosed with TSC. Methods: Of 105 children (<18 years) with epilepsy due to FCD who underwent presurgical evaluation between 2002-06 at the Cleveland Clinic Foundation, five (3 females) with an initial diagnosis of FCD on the brain MRI, had a final diagnosis of TSC in the absence of classical brain TSC findings. All met clinical TSC criteria with (4/5) or without (1/5) TSC gene mutations. We reviewed clinical data, brain MRI, DNA results, seizure outcome, and pathological findings in these 5 patients. Results: Age of seizure onset was 2days-10 years (median 9 months). On video EEG, four were infants with frequent daily spasms (2/4) or hypomotor and focal tonic clonic limb seizures (2/4), and one was a 10 year-old with right motor seizures. Brain MRI showed solitary left frontal FCD in two (1 with calcification), and right frontal, left parietal and right posterior quadrant FCD in one each. TSC was considered due to discovery of hypopigmented macules in 3 infants on Wood’s lamp examination, cardiac rhabdomyomas in 1 infant who underwent Echo during an intensive care admission for seizures and hypotension, and due to a positive family history of seizures and FCD calcification in the 10 year-old child. On further tests, all (5/5) had hypopigmented macules (>3, with no other cutaneous findings) on Wood’s lamp examination, all infants (4/5) had cardiac rhadbomyomas on Echo, 1/5 had renal cysts, 1/5 had a family history of seizures due to TSC. Eye exam was normal in all. Three had definite or highly probable mutation in TSC 1 (2) and TSC 2 (1) genes, one had possible TSC2 missense mutation, and no mutation was found in one who only had TSC1 gene sequencing. Four underwent epilepsy surgery. After surgery (follow up 2-24 months), all were seizure free on 1 (3/4) or 2 (1/4) antiepileptic medications. Surgical pathology showed cortical dysplasia in all without any characteristic features of TSC. Conclusions: Solitary FCD, the most common sporadic pathological substrate of partial epilepsy in children, may be the only brain MRI finding in TSC. When FCD is associated with seizure onset in early infancy, family history of seizures or calcification, diagnosis of TSC should be considered. Cardiac Echo in infants and Wood’s lamp examination were most helpful in the clinical diagnosis of TSC. Early diagnosis of TSC is critical as rapamycin is reported to be efficacious in treating TSC related morbidity. We acknowledge Dr. David Kwiatkowski, Professor of Medicine, Harvard Medical School for help with DNA results.