Opportunities to improve patient management included increasing the proportion with a pathologically confirmed diagnosis and greater use of postsurgical adjuvant chemotherapy. A high proportion of patients received no treatment, with underuse of chemotherapy and radiotherapy. Critically, the low rate of case discussions at MDMs needs to increase. However, effective strategies are required to identify cases early, as over two-thirds currently present with incurable disease.

The authors analyzed the association between APOE epsilon4 genotype and clinical and MRI findings in 43 refractory temporal lobe epilepsy patients. The distribution of the alleles were normal. Ten patients (23%) had an APOE epsilon 4 allele and had an earlier onset of habitual seizures (with epsilon4 5 +/- 5 years; without epsilon4 15 +/- 10 years). Quantitative MRI findings were not influenced by the APOE epsilon4 genotype. APOE epsilon4 may shorten the latency between an initial injury and seizure onset.

Objective: Analysis of twins with epilepsy to explore the genetic architecture of specific epilepsies, to evaluate the applicability of the 2010 International League Against Epilepsy (ILAE) organization of epilepsy syndromes, and to integrate molecular genetics with phenotypic analyses.Methods: A total of 558 twin pairs suspected to have epilepsy were ascertained from twin registries (69%) or referral (31%). Casewise concordance estimates were calculated for epilepsy syndromes. Epilepsies were then grouped according to the 2010 ILAE organizational scheme. Molecular genetic information was utilized where applicable.Results: Of 558 twin pairs, 418 had confirmed seizures. A total of 534 twin individuals were affected. There were higher twin concordance estimates for monozygotic (MZ) than for dizygotic (DZ) twins for idiopathic generalized epilepsies (MZ 5 0.77; DZ 5 0.35), genetic epilepsy with febrile seizures plus (MZ 5 0.85; DZ 5 0.25), and focal epilepsies (MZ 5 0.40; DZ 5 0.03). Utilizing the 2010 ILAE scheme, the twin data clearly demonstrated genetic influences in the syndromes designated as genetic. Of the 384 tested twin individuals, 10.9% had mutations of large effect in known epilepsy genes or carried validated susceptibility alleles.Conclusions: Twin studies confirm clear genetic influences for specific epilepsies. Analysis of the twin sample using the 2010 ILAE scheme strongly supported the validity of grouping the "genetic" syndromes together and shows this organizational scheme to be a more flexible and biologically meaningful system than previous classifications. Successful selected molecular testing applied to this cohort is the prelude to future large-scale next-generation sequencing of epilepsy research cohorts. Insights into genetic architecture provided by twin studies provide essential data for optimizing such approaches. Neurology ® 2014;83:1042-1048 GLOSSARY BECTS 5 benign epilepsy with centrotemporal spikes; CAE 5 childhood absence epilepsy; DS 5 Dravet syndrome; DZ 5 dizygotic; FE 5 focal epilepsies; FS 5 febrile seizures; FS1 5 febrile seizures plus; GE 5 generalized epilepsies; GEFS1 5 genetic epilepsy with febrile seizures plus; IFE 5 idiopathic focal epilepsies; IGE 5 idiopathic generalized epilepsies; ILAE 5 International League Against Epilepsy; IPOE 5 idiopathic photosensitivity occipital epilepsy; JME 5 juvenile myoclonic epilepsy; MAS 5 epilepsy with myoclonic-atonic seizures; MZ 5 monozygotic; SGE 5 symptomatic generalized epilepsies; SSCP 5 single-stranded conformation polymorphism; TLE 5 temporal lobe epilepsy.