RESUMEN
Cerebral cavernous malformation (CCM) is a vascular malformation of the central nervous system which may occur sporadically or segregate within families due to heterozygous variants in KRIT1/CCM1, MGC4607/CCM2 or PDCD10/CCM3. Intronic variants are not uncommon in familial CCM, but their clinical interpretation is often hampered by insufficient data supporting in silico predictions. Here, the mRNA analysis for two intronic unpublished variants (KRIT1 c.1147-7 T > G and PDCD10 c.395 + 2 T > G) and three previously published variants in KRIT1 but without data supporting their effects was carried out. This study demonstrated that all variants can induce a frameshift with the lack of residues located in the C-terminal regions and involved in protein-protein complex formation, which is essential for vascular homeostasis. These results support the introduction of mRNA analysis in the diagnostic pathway of familial CCM and expand the knowledge of abnormal splicing patterning in this disorder.
Asunto(s)
Proteínas Reguladoras de la Apoptosis/genética , Proteína KRIT1/genética , Proteínas de la Membrana/genética , Mutación/genética , Proteínas Proto-Oncogénicas/genética , Hemangioma Cavernoso del Sistema Nervioso Central/genética , Humanos , Empalme del ARN/genética , ARN Mensajero/genéticaAsunto(s)
Seno Frontal/lesiones , Cefalea/diagnóstico , Hipotensión Intracraneal/diagnóstico , Neumocéfalo/diagnóstico , Estornudo , Anciano , Seno Frontal/diagnóstico por imagen , Cefalea/etiología , Cefalea/terapia , Humanos , Hipotensión Intracraneal/terapia , Imagen por Resonancia Magnética , Masculino , Neumocéfalo/etiología , Neumocéfalo/terapiaRESUMEN
BACKGROUND: Perampanel (PER) is a novel antiepileptic drug approved as an add-on therapy for focal onset seizures with or without generalization and primary generalized tonic-clonic seizures. Aim of this study was to evaluate PER efficacy and tolerability as add-on therapy in patients with drug-resistant focal onset seizures and especially temporal lobe epilepsy (TLE). METHODS: An observational, prospective, multicentre study on adult with drug-resistant focal epilepsy consecutively recruited from six Italian tertiary epilepsy centres. All patients received add-on PER according to indication and clinical judgement. Seizure frequency and adverse events (AEs) were recorded at 6 and 12â¯months after PER introduction. RESULTS: Study sample comprised 246 patients, 77 of which with TLE. Seventy-five (35.9%) out of 209 and 66 (38.8%) out of 170 patients still taking PER resulted to be responders (i.e. ≥50% of seizure frequency or seizure free) after six and 12â¯months, respectively. In the TLE group, 39 (57.3%) out of 68 subjects on PER after 6â¯months and 32 (60.4%) out of 53 subjects taking PER after 12â¯months were responders. Overall reported incidence of AEs was 26.1%. In 28 cases (11.3%) AEs lead/contributed to PER discontinuation. The most frequently reported AE were dizziness (14/84) and somnolence (14/84). Regarding TLE patients, 25.9% of them experienced at least one AE and discontinuation for AEs occurred in eight (10.4%). CONCLUSIONS: This study confirmed the good efficacy and safety of PER for drug-resistant focal epilepsy in real-life conditions and, above all, for the first time provide its effectiveness in patients with TLE.