Biomedical subjects

Carla Marini

Publications and source records attributed to Carla Marini.

22 records · Page 2Linked to original sources

PubMed2003

EEG in adult-onset idiopathic generalized epilepsy.

PURPOSE: It remains controversial whether adult-onset idiopathic generalized epilepsy (IGE) is a distinct syndrome or a continuum among IGE syndromes. EEG is the only known biologic marker of IGE and helps differentiate many of its classic subsyndromes. In this study, we looked for the differences in the EEG findings of IGE of classic adolescent onset versus adult onset that may suggest syndromic heterogeneity. METHODS: Seventy-six patients (47 adolescent-onset IGE, 29 adult-onset IGE) with a clinical and EEG diagnosis of IGE were included. We defined IGE with age at onset of 11-20 years as adolescent-onset IGE and age at onset of 20 years or after as adult-onset IGE. Patients with first-decade onset of seizures, delayed EEGs, and no EEG available for review were excluded. The first EEG was performed within 24 h of the seizure, and if negative, a sleep-deprived EEG was done. All EEGs were reviewed in detail with respect to the background activity and the generalized spike-wave (GSW) characteristic. RESULTS: EEGs (87; 56 adolescent-onset IGE, 31 adult-onset IGE) were systematically reviewed. Background was normal in all patients. The morphology, amplitude, duration, frequency, occurrence, or activation of the GSW pattern did not differ between these two groups. CONCLUSIONS: No differences of EEG features were found between the classic adolescent-onset and the adult-onset IGE. This supports the hypothesis that they share common biologic determinants and exist along a life-long age spectrum of classic IGE.

Adolescent↗

PubMed2003

Childhood absence epilepsy and febrile seizures: a family with a GABA(A) receptor mutation.

Although several genes for idiopathic epilepsies from families with simple Mendelian inheritance have been found, genes for the common idiopathic generalized epilepsies, where inheritance is complex, presently are elusive. We studied a large family with epilepsy where the two main phenotypes were childhood absence epilepsy (CAE) and febrile seizures (FS), which offered a special opportunity to identify epilepsy genes. A total of 35 family members had seizures over four generations. The phenotypes comprised typical CAE (eight individuals); FS alone (15), febrile seizures plus (FS(+)) (three); myoclonic astatic epilepsy (two); generalized epilepsy with tonic-clonic seizures alone (one); partial epilepsy (one); and unclassified epilepsy despite evaluation (two). In three remaining individuals, no information was available. FS were inherited in an autosomal dominant fashion with 75% penetrance. The inheritance of CAE in this family was not simple Mendelian, but suggestive of complex inheritance with the involvement of at least two genes. A GABA(A) receptor gamma2 subunit gene mutation on chromosome 5 segregated with FS, FS(+) and CAE, and also occurred in individuals with the other phenotypes. The clinical and molecular data suggest that the GABA(A) receptor subunit mutation alone can account for the FS phenotype. An interaction of this gene with another gene or genes is required for the CAE phenotype in this family. Linkage analysis for a putative second gene contributing to the CAE phenotype suggested possible loci on chromosomes 10, 13, 14 and 15. Examination of these loci in other absence pedigrees is warranted.

Adult↗

PubMed2002

Altered kinetics and benzodiazepine sensitivity of a GABAA receptor subunit mutation [gamma 2(R43Q)] found in human epilepsy.

The gamma-aminobutyric acid type A (GABA(A)) receptor mediates fast inhibitory synaptic transmission in the CNS. Dysfunction of the GABA(A) receptor would be expected to cause neuronal hyperexcitability, a phenomenon linked with epileptogenesis. We have investigated the functional consequences of an arginine-to-glutamine mutation at position 43 within the GABA(A) gamma(2)-subunit found in a family with childhood absence epilepsy and febrile seizures. Rapid-application experiments performed on receptors expressed in HEK-293 cells demonstrated that the mutation slows GABA(A) receptor deactivation and increases the rate of desensitization, resulting in an accumulation of desensitized receptors during repeated, short applications. In Xenopus laevis oocytes, two-electrode voltage-clamp analysis of steady-state currents obtained from alpha(1)beta(2)gamma(2) or alpha(1)beta(2)gamma(2)(R43Q) receptors did not reveal any differences in GABA sensitivity. However, differences in the benzodiazepine pharmacology of mutant receptors were apparent. Mutant receptors expressed in oocytes displayed reduced sensitivity to diazepam and flunitrazepam but not the imidazopyridine zolpidem. These results provide evidence of impaired GABA(A) receptor function that could decrease the efficacy of transmission at inhibitory synapses, possibly generating a hyperexcitable neuronal state in thalamocortical networks of epileptic patients possessing the mutant subunit.

Amino Acid Substitution↗

PubMed2002

Partial epilepsy with prominent auditory symptoms not linked to chromosome 10q.

Autosomal dominant partial epilepsy with auditory features (ADPEAF) has been identified as a distinct genetic syndrome. Several families have been described linked to chromosome 10q24, which carries mutations in the LGI1 gene. We report a small new pedigree with partial epilepsy with auditory symptoms. We performed a detailed clinical study of the family, constructed an extended pedigree comprising 106 individuals, and obtained blood samples for genetic analysis. Individuals with seizures also underwent neurophysiological and neuroradiological investigations. Genetic analysis was performed with six microsatellite markers spanning to the critical region of chromosome 10q24. Mutation analysis of the coding sequence of LGI1 was performed in two patients. Five members of the family in generation IV had seizures. Three individuals had auditory auras, followed by generalised seizures in two and brief loss of contact in one, one had nocturnal tonic-clonic seizures with an EEG suggestive of right temporal lobe onset, and one only had febrile seizures. In addition, a deceased woman was said to have had seizures. Haplotype analysis of this region of chromosome 10q24 failed to disclose a common haplotype in affected family members and no disease-associated mutations were detected in the LGI1 gene, suggesting that this locus is not associated with the disease in our family. Our small sample with partial epilepsy with auditory symptoms, clinically resembles previously described ADPEAF families. However, the low number of patients is compatible with either autosomal dominant or other inheritance patterns. In the case of the former, the lack of segregation with 10q24 suggests that a second locus is involved in the aetiology of ADPEAF; in the latter, an epileptic syndrome also characterized by auditory features, but distinct from ADPEAF, could be transmitted in this family.

Adult↗