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Isabelle Gourfinkel-An

Publications and source records attributed to Isabelle Gourfinkel-An.

6 recordsLinked to original sources
PubMed2006

Basilar artery diameter and 5-year mortality in patients with stroke.

BACKGROUND AND PURPOSE: Few and conflicting data exist on the case fatality rate in stroke patients with basilar artery dolichoectasia. We analyzed basilar artery characteristics (diameter, height of bifurcation, transverse position) and 5-year mortality (all-cause, nonstroke vascular, and stroke) in patients with brain infarction. METHODS: The basilar artery diameter was measured with a 16-diopter lens in 466 consecutively recruited patients with brain infarction confirmed by magnetic resonance imaging. The height of the bifurcation and the transverse position of the basilar artery were assessed on semiquantitative scales. Patients were followed up for a median of 5.3 years (range, 1.5 to 6.6) and were classified as having had stroke, nonstroke vascular, and nonvascular death according to the French national registry of death certificates. RESULTS: Of the 157 deaths, 88 were vascular (including 54 stroke deaths). Basilar artery diameter was associated with an increased 5-year stroke mortality rate but not with all-cause or nonstroke vascular mortality. The adjusted hazard ratio (HR) of stroke mortality per 1-mm increase in basilar artery diameter was 1.23 (95% confidence interval [CI], 1.07 to 1.41). A higher risk of stroke death was associated with basilar artery diameter at the 95th percentile (diameter >4.3 mm; adjusted HR 3.69; 95% CI, 1.63 to 8.38) and the height of bifurcation (adjusted HR for score >1, 2.08; 95% CI, 0.93 to 4.68) but not with transverse position. CONCLUSIONS: Basilar artery diameter was independently associated with cerebrovascular mortality. A diameter >4.3 mm may be a marker for a high risk of fatal stroke.

Aged↗
PubMed2006

Parental mosaicism can cause recurrent transmission of SCN1A mutations associated with severe myoclonic epilepsy of infancy.

De novo mutations in the SCN1A gene, encoding the alpha1-subunit of the neuronal voltage-gated sodium channel Nav1.1, are the most frequent genetic cause of Severe Myoclonic Epilepsy of Infancy known so far. A few mutations inherited from an asymptomatic or mildly affected parent have been reported, suggesting that expression of the mutated gene may be variable in the transmitting parent. In this study, we report two unrelated families in which two children of unaffected parents had deleterious SCN1A mutations, and show evidence of somatic and germline mosaicism in the transmitting parents. In one of these families, direct sequencing of blood cell DNA was not sufficient to the SCN1A mutation in the transmitting asymptomatic parent who was mosaic for the mutation. We therefore developed a real-time PCR assay to selectively amplify and quantify the mutant allele present at low levels in the transmitting parent in both families. The allele-specific PCR technique used in this study will be of use in detecting other such cases. These findings will have major consequences for the genetic counseling of asymptomatic parents with only one affected child.

Adult↗
PubMed2004

Monogenic idiopathic epilepsies.

Major advances have recently been made in our understanding of the genetic bases of monogenic inherited epilepsies. Direct molecular diagnosis is now possible in numerous inherited symptomatic epilepsies. Progress has also been spectacular with respect to several idiopathic epilepsies that are caused by mutations in genes encoding subunits of ion channels or neurotransmitter receptors. Although these findings concern only a few families and sporadic cases, their potential importance is great, because these genes are implicated in a wide range of more common epileptic disorders and seizure types as well as some rare syndromes. Functional studies of these mutations, while leading to further progress in the neurobiology of the epilepsies, will help to refine genotype-phenotype relations and increase our understanding of responses to antiepileptic drugs. In this article, we review the clinical and genetic data on most of the idiopathic human epilepsies and epileptic contexts in which the association of epilepsy and febrile convulsions is genetically determined.

Animals↗
PubMed2004

Fever, genes, and epilepsy.

About 13% of patients with epilepsy have a history of febrile seizures (FS). Studies of familial forms suggest a genetic component to the epidemiological link. Indeed, in certain monogenic forms of FS, for which several loci have been reported, some patients develop epilepsy with a higher risk than in the general population. Patients with generalised epilepsy with febrile seizures plus (GEFS+) can have typical and isolated FS, FS lasting more beyond age 6 years, and subsequent afebrile (typically generalised) seizures. Mutations associated with GEFS+ were identified in genes for subunits of the voltage-gated sodium channel and the gamma2 subunit of the ligand-gated GABAA receptor. Screening for these genes in patients with severe myoclonic epilepsy in infancy showed de novo mutations of the alpha1 subunit of the voltage-gated sodium channel. Antecedent FS are commonly observed in temporal-lobe epilepsy (TLE). In sporadic mesial TLE-characterised by the sequence of complex FS in childhood, hippocampal sclerosis, and refractory temporal-lobe seizures-association studies suggested the role of several susceptibility genes. Work on some large pedigrees also suggests that FS and temporal-lobe seizures may have a common genetic basis, whether hippocampus sclerosis is present or not. The molecular defects identified in the genetic associations of FS and epileptic seizures are very attractive models to aid our understanding of epileptogenesis and susceptibility to seizure-provoking factors, especially fever.

Epilepsy↗
PubMed2002

Metabolic changes in the basal ganglia of patients with Huntington's disease: an in situ hybridization study of cytochrome oxidase subunit I mRNA.

On the basis of the functional model of the basal ganglia developed in the 1980s and the neuropathological findings in Huntington's disease (HD), changes in the neuronal activity of the basal ganglia have previously been proposed to explain the abnormal movements observed in this pathology. In particular, it has been stated that the neurodegenerative process affecting the basal ganglia in the disease should provoke a hypoactivity in the internal segment of the pallidum (GPi) that could explain choreic movements observed in the disease. To test this functional hypothesis, we performed an in situ hybridization study on control and HD brains postmortem, taking cytochrome oxidase subunit I (COI) mRNAs expression as index of neuronal activity. As most of the HD patients studied were under chronic neuroleptic (NL) treatment, we also studied the brains of non-HD patients under chronic NL treatment. Our results show that in HD brain the number of neurons expressing COI mRNA tends to be lower in the striatum, GPe and GPi, suggesting a severe involvement of these structures during the neurodegenerative process. Moreover, COI mRNA level of expression was markedly reduced within neurons of the putamen and GPe. Surprisingly, COI mRNA expression was not modified in the GPi in HD brains compared with controls. This paradoxical result in the GPi may be explained by the antagonistic effect of GPe hypoactivity and the degenerative process involving neurons of GPi. Our results indicate that the functional modifications, and consequently the pathophysiology of abnormal movements, observed in HD basal ganglia are more complex than expected from the currently accepted model of the basal ganglia organization.

Adult↗