RESUMEN
Spontaneous intracranial hypotension is a rare condition caused by spontaneous cerebrospinal fluid leak. It is characterised by orthostatic headache, diffuse pachymeningeal enhancement on brain imaging and low cerebrospinal fluid pressure. Seven patients with spontaneous intracranial hypotension were treated conservatively: of these, four responded to drug treatment and three underwent a lumbar autologous epidural blood patch (EBP). A complete response was obtained in two patients after a single EBP; one patient underwent a second EBP and then became asymptomatic. Clinical improvement coincided with a dramatic reduction of pachymeningeal enhancement. The aetiology and brain imaging findings, and the technique and effectiveness of EBP are discussed.
Asunto(s)
Parche de Sangre Epidural , Hipotensión Intracraneal/etiología , Hipotensión Intracraneal/terapia , Adulto , Encéfalo/patología , Pérdida de Líquido Cefalorraquídeo , Rinorrea de Líquido Cefalorraquídeo/complicaciones , Femenino , Cefalea/etiología , Humanos , Hipotensión Intracraneal/tratamiento farmacológico , Imagen por Resonancia Magnética , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: To characterize clinically and genetically a family with autosomal dominant lateral temporal epilepsy (ADLTE) negative to LGI1 exon sequencing test. METHODS: All participants were personally interviewed and underwent neurologic examination. Most affected subjects underwent EEG and neuroradiologic examinations (CT/MRI). Available family members were genotyped with the HumanOmni1-Quad v1.0 single nucleotide polymorphism (SNP) array beadchip and copy number variations (CNVs) were analyzed in each subject. LGI1 gene dosage was performed by real-time quantitative PCR (qPCR). RESULTS: The family had 8 affected members (2 deceased) over 3 generations. All of them showed GTC seizures, with focal onset in 6 and unknown onset in 2. Four patients had focal seizures with auditory features. EEG showed only minor sharp abnormalities in 3 patients and MRI was unremarkable in all the patients examined. Three family members presented major depression and anxiety symptoms. Routine LGI1 exon sequencing revealed no point mutation. High-density SNP array CNV analysis identified a genomic microdeletion about 81 kb in size encompassing the first 4 exons of LGI1 in all available affected members and in 2 nonaffected carriers, which was confirmed by qPCR analysis. CONCLUSIONS: This is the first microdeletion affecting LGI1 identified in ADLTE. Families with ADLTE in which no point mutations are revealed by direct exon sequencing should be screened for possible genomic deletion mutations by CNV analysis or other appropriate methods. Overall, CNV analysis of multiplex families may be useful for identifying microdeletions in novel disease genes.
Asunto(s)
Epilepsia del Lóbulo Temporal/genética , Proteínas/genética , Eliminación de Secuencia , Adolescente , Adulto , Anticonvulsivantes/uso terapéutico , Ansiedad/complicaciones , Carbamazepina/análogos & derivados , Carbamazepina/uso terapéutico , Trastorno Depresivo Mayor/complicaciones , Electroencefalografía , Epilepsia del Lóbulo Temporal/complicaciones , Epilepsia del Lóbulo Temporal/diagnóstico , Epilepsia del Lóbulo Temporal/tratamiento farmacológico , Femenino , Humanos , Péptidos y Proteínas de Señalización Intracelular , Escala de Lod , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Examen Neurológico , Oxcarbazepina , Linaje , Adulto JovenRESUMEN
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.