Tuberous sclerosis complex (TSC) is an autosomal-dominant inheritable neurocutaneous disease due to mutations within the TSC1 and TSC2 genes. Many patients present with West syndrome, a severe epilepsy syndrome characterized by the triad of infantile spasms, an interictal electroencephalogram (EEG) pattern termed hypsarrhythmia (continuous slow activity with an amplitude higher than 300 µV and multiregional spikes/polyspikes/sharp waves) and developmental regression. In this study, we report on a previously healthy patient with positive family history of epilepsy with new-onset epileptic encephalopathy at the age of 9 years. Clinical signs alone were not sufficient to establish the diagnosis of TSC but epilepsy panel screening revealed a novel frameshift mutation (c.90delA; p.Glu31Argfs*12) within the TSC1 gene. Segregation gene analysis detected the same mutation in the mother. Cranial magnetic resonance imaging (MRI) studies from the index patient and his mother revealed a similar pattern of isolated subcortical white matter lesions resembling most likely focal cortical dysplasia (FCD) type IIb. In summary, in these 2 related patients, a novel TSC1 frameshift mutation was associated with an isolated FCD type IIb in the absence of further CNS abnormalities usually encountered in patients with TSC, fostering our understanding of the broad mutation spectra in the TSC1 gene and the close relationship between cortical tubers and FCD type IIb.

Focal cortical dysplasia (FCD) is a common cause of medically intractable epilepsy in children. Epilepsy surgery has been a valuable treatment option to achieve seizure freedom in these intractable epilepsy patients. We aimed to present long-term surgical outcome, in relation to pathological severity, and to assess predictive factors of epilepsy surgery in pediatric isolated FCD. We retrospectively analyzed the data of 58 children and adolescents, with FCD International League Against Epilepsy (ILAE) task force classification types I and II, who underwent resective epilepsy surgery and were followed for at least 2 years after surgery. The mean age at epilepsy onset was 4.3 years (0-14.2 years), and mean age at epilepsy surgery was 9.4 years (0.4-17.5 years). The mean duration of postoperative follow-up was 5.1±2.6 years (2-12.4 years). Of 58 patients, 62% of patients achieved Engel class I at 2 years postoperatively, 58% at 5 years postoperatively, and 53% at the last follow up. Forty eight percent of our cohort successfully discontinued antiepileptic medication. Of 30 patients with seizure recurrence, 83% of seizures recurred within 2 years after surgery. We observed that FCD type IIb was significantly associated with a better surgical outcome. At fifth postoperative year, 88% of FCD IIb patients were seizure free compared with 21% of type I and 57% of type IIa patients (P=0.043). By multivariate analysis, lesion on MRI (P=0.02) and complete resection (P<0.01) were the most important predictive factors for a seizure-free outcome. Epilepsy surgery is highly effective; more than half of medically intractable epilepsy patients achieved seizure freedom after surgery. In addition, we found significant difference in surgical outcomes according to the ILAE task force classification. Lesion on MRI and complete resection were the most important predictive factors for favorable seizure outcome in isolated FCD patients.

The aim of the current study was to evaluate the factors associated with post-operative outcome in patients with temporal lobe epilepsy (TLE) undergoing Surgery. We analyzed data of 288 consecutive patients operated for drug-resistant TLE. All the patients had at least one year post surgery follow-up. Logistic regression model was used to evaluate the predictive value of different factors for outcome. The mean age at onset of epilepsy of the study population was 15.51 ± 9.79 years; whereas the mean age at surgery was 32.16 ± 9.45 years, with 125 (43.4%) women. The age at surgery was significantly lower in the patients with favourable outcome (30.26 ± 9.05 vs. 34.06 ± 9.85 years; p = 0.007). The mean duration of epilepsy with age of onset below 12 years was higher than the rest (19.84 ± 7.30 vs. 13.00 ± 8.45 years; p < 0.001). The histopathology showed hippocampal sclerosis in 203 (70.4%) of the patients; isolated focal cortical dysplasia was associated with unfavourable outcome (9.3% vs.2.6%; p = 0.036). The duration of follow up ranged from 1 to 10.3 years. Three patients died late in the follow up. At the last follow 73% were seizure free and Engel's favourable outcome was noted in 82%. Duration of epilepsy greater than ten years (β = 6.997; 95%CI; 2.254-21.715; p = 0.01), younger age of onset of epilepsy (β = 1.07; 95%CI; 1.014-1.132; p = 0.015) and acute post operative seizures (APOS) (β = 4.761; 95%CI; 1.946-11.649; p = 0.001) were the predictors of unfavourable outcome. Following surgery for TLE, 73% were seizure free and Engel's favourable outcome was noted in 82%. The predictors of unfavourable outcome were younger age of onset, pronged duration and of epilepsy and APOS.

It has been postulated that mitochondrial dysfunction may be an important factor in epileptogenesis of intractable epilepsy. The current study tests the hypothesis that mitochondrial Complex IV (CIV) or cytochrome c oxidase dysfunction is associated with the seizure onset zone (SOZ) in patients with focal cortical dysplasia (FCD). Subjects were selected based on: age <19y; epilepsy surgery between May, 2010 and October, 2011; pathological diagnosis of isolated focal cortical dysplasia Type I (FCDI) or Type II (FCDII); and sufficient residual cortical tissue to conduct analysis of electron transport chain complex (ETC) activity in SOZ and adjacent cortical regions. In this retrospective study, patients were identified who had sufficient unfixed, frozen brain tissue for biochemical analysis in tissue homogenates. Specimens were subtyped using ILAE classification for FCD, and excluded if diagnosed with FCD Type III or dual pathology. Analysis of ETC activity in resected tissues was conducted independently and without knowledge of the identity, diagnosis, or clinical status of individual subjects. Seventeen patients met the inclusion criteria, including 6 FCDI and 11 FCDII. Comparison of adjacent cortical resections showed decreased CIV activity in the SOZ of the FCDII group (P = 0.003), but no significant CIV difference in adjacent tissues of the FCDI group. Because of the importance of CIV as the terminal and rate-limiting complex in the mitochondrial electron transport chain, these authors conclude that 1) a deficit of CIV is associated with the SOZ of patients with FCDII; 2) CIV deficiency may contribute to the spectrum of FCD neuropathology; and 3) further investigation of CIV in FCD may lead to the discovery of new targets for neuroprotective therapies for patients with intractable epilepsy.