Familial temporal lobe epilepsy with psychic auras associated with a novel LGI1 mutation.

BACKGROUND: Autosomal dominant lateral temporal epilepsy (ADLTE) is characterized by focal seizures with auditory features or aphasia. Mutations in the LGI1 gene have been reported in up to 50% of ADLTE pedigrees. We report a family with temporal lobe epilepsy characterized by psychic symptoms associated with a novel LGI1 mutation. METHODS: All participants were personally interviewed and underwent neurologic examination and video-EEG recordings. LGI1 exons were sequenced by standard methods. Mutant cDNA was transfected into human embryonic kidney 293 cells; both cell lysates and media were analyzed by Western blot. In silico modeling of the Lgi1 protein EPTP domain was carried out using the structure of WD repeat protein and manually refined. RESULTS: Three affected family members were ascertained, 2 of whom had temporal epilepsy with psychic symptoms (déjà vu, fear) but no auditory or aphasic phenomena, while the third had complex partial seizures without any aura. In all patients, we found a novel LGI1 mutation, Arg407Cys, which did not hamper protein secretion in vitro. Mapping of the mutation on a 3-dimensional protein model showed that this mutation does not induce large structural rearrangements but could destabilize interactions of Lgi1 with target proteins. CONCLUSIONS: The Arg407Cys is the first mutation with no effect on Lgi1 protein secretion. The uncommon, isolated psychic symptoms associated with it suggests that ADLTE encompasses a wider range of auras of temporal origin than hitherto reported.

[Small-cell lung tumors: is a more accurate staging possible and useful?]. / Tumore polmonare a piccole cellule: è possibile e utile la stadiazione più accurata?

Small cell lung cancer is generally staged as a localized or diffuse disease due to its great invasiveness and quick spread. The authors investigated the advantages of a more accurate staging by TNM system applied to small cell lung cancer. Sixteen patients (12 males and 4 females, mean age 54 years, max 66, min 48) were submitted to a treatment protocol consisting of 6 cycles of chemotherapy over an 18-month period. All patients underwent CT before and after the third and sixth cycles. Disease evolution was evaluated by means of the TNM system; relative to the N parameter, the American Thoracic Society criteria were followed. After completion of the third chemotherapy cycle, CT demonstrated reduction in T in 7/16 cases, while in the extant patients T was unchanged. N decreased too in 7 patients and remained unchanged in the others. CT examinations at the end of the whole treatment protocol demonstrated no changes in T. As for N, CT showed evolution from N0 to N2 in one case and from N3 to N0 in another one, while no changes were observed in the extant patients. The M parameter was constantly negative in all cases. Our results demonstrate that this approach to small cell lung cancer permits a more accurate characterization of the disease, thus making it easier to monitor the positive/negative response to treatment and allowing the latter to be personalized.