Biomedical subjects

I Lopes-Cendes

Publications and source records attributed to I Lopes-Cendes.

46 records · Page 3Linked to original sources

PubMed1995

Genetic linkage studies in familial frontal epilepsy: exclusion of the human chromosome regions homologous to the El-1 mouse locus.

Familial frontal epilepsy has been recently described in six pedigrees. All families reported show autosomal dominant inheritance with incomplete penetrance. Affected individuals develop predominantly nocturnal seizures with frontal lobe semiology. In 1959, a genetic mouse model for partial epilepsy, the El mouse, was reported. In the El mouse, a major seizure susceptibility gene, El-1, segregates in an autosomal dominant fashion and has been localized to a region distal to the centromere of mouse ch 9. Comparative genetic maps between man and mouse have been used to predict the location of several human disease genes. The El-1 locus in the mouse is homologous to human chromosomes 3p23-p21.2, 3p11.2-q11.2, 3q21-q25.3, 6p12-q12 and 15q24. Polymorphic microsatellite markers covering these candidate regions were used for genotyping individuals in the three larger families ascertained, one of which is French-Canadian and two are Australian. Significant negative two-point and multipoint lod scores were obtained separately for each family, thus excluding linkage with the candidate regions on chromosomes 3, 6 and 15.

Animals↗

PubMed1995

Autosomal dominant nocturnal frontal lobe epilepsy. A distinctive clinical disorder.

The disorder of autosomal dominant nocturnal frontal lobe epilepsy has recently been identified, and is now delineated in detail. A phenotypically homogeneous group of five families from Australia, Britain and Canada, containing 47 affected individuals, was studied. The largest family contained 25 affected individuals spanning six generations. This disorder is characterized by clusters of brief nocturnal motor seizures, with hyperkinetic or tonic manifestations. Subjects often experienced an aura, and remained aware throughout the attacks. Seizures occurred in clusters (mean eight attacks/night) typically as the individual dozed, or shortly before awakening. The epilepsy usually began in childhood, and persisted through adult life, with considerable intra-family variation in severity. Seizures were often misdiagnosed as benign nocturnal parasomnias, psychiatric and medical disorders. Interictal EEG studies were unhelpful. Ictal video-EEG studies showed that the attacks were partial seizures with frontal lobe seizure semiology. Neuro-imaging was normal. Carbamazepine monotherapy was frequently effective. This disorder showed autosomal dominant inheritance. Recognition of this entity is clinically important for diagnosis, appropriate therapy and genetic counselling. Moreover, this disorder now offers an opportunity to identify a gene for partial epilepsy.

Adolescent↗

PubMed1994

Evidence for the existence of a fourth dominantly inherited spinocerebellar ataxia locus.

The autosomal dominantly inherited spinocerebellar ataxias (SCAs) are a heterogeneous group of disorders. To date, three loci have been identified: the SCA1 locus (on chr 6p), the SCA2 locus (on chr 12q), and more recently a Machado-Joseph disease (MJD) locus (on chr 14q). We have studied one large French-Canadian kindred with four generations of living affected individuals segregating an autosomal dominant form of SCA. Linkage analysis using anonymous DNA markers that flank the three previously described loci significantly exclude the French-Canadian kindred from the SCA1, SCA2, and MJD loci. Therefore, a fourth, still unmapped SCA locus remains to be identified. In addition, the unique clinical phenotype present in all affected individuals of the French-Canadian kindred might be characteristic of this still unmapped SCA locus.

Canada↗

PubMed1994

Autosomal dominant frontal epilepsy misdiagnosed as sleep disorder.

We describe a distinctive epilepsy syndrome in six families, which is the first partial epilepsy syndrome to follow single gene inheritance. The predominant seizure pattern had frontal lobe seizure semiology with clusters of brief motor attacks occurring in sleep. Onset was usually in childhood, often persisting through adult life. Misdiagnosis as night terrors, nightmares, hysteria, or paroxysmal nocturnal dystonia was common, and the inheritance pattern was often not appreciated. This autosomal dominant epilepsy syndrome is ideal for identification of partial epilepsy genes.

Adolescent↗

PubMed1994

Relationship between atrophy of the amygdala and ictal fear in temporal lobe epilepsy.

Viscerosensory and affective manifestations are often elicited by temporal lobe seizure discharges. They have been reproduced by amygdaloid stimulation in awake patients during stereotaxic exploration or neurosurgical procedures. They are not exclusively reproduced by stimulation of the amygdala, though most commonly they are evoked from it. Ictal fear is frequently, but not invariably, associated with a rising epigastric sensation, palpitations, mydriasis and pallor. We studied 50 patients (mean age 33 years) with intractable temporal lobe epilepsy (TLE): MRI volumetric measurements of amygdala and hippocampus were performed using a protocol previously described by our group (Watson et al., Neurology 1992; 42: 1743-50). All patients had extensive EEG investigation and at least two seizures recorded by video-EEG monitoring. Seventeen patients (34%) had a clear history of fear accompanied by a rising epigastric sensation as the initial manifestation of their habitual attacks. The amygdala volumes in this group were significantly (P = 0.001) smaller (mean 2131.6 mm3) compared with the volumes of the 33 patients without these symptoms (mean 2561.5 mm3). Both patient groups had smaller mean amygdala volumes compared with normal controls (mean 2828.2 mm3). Postoperative pathology correlated well with volumetric atrophy. In addition, we found that patients with more pronounced amygdaloid atrophy more commonly had prolonged febrile convulsions in early childhood and also more frequently secondarily generalized seizures. Results support the finding that ictal fear is related to pathology of the amygdala and that it, like the hippocampus, is an important substrate of TLE.

Adolescent↗

PubMed1994

Confirmation of the SCA-2 locus as an alternative locus for dominantly inherited spinocerebellar ataxias and refinement of the candidate region.

The autosomal dominant spinocerebellar ataxias (SCAs) are a clinically heterogeneous group of neurodegenerative diseases. To date, two SCA loci have been identified-one locus (SCA-1) on the short arm of chromosome 6 and the second locus (SCA-2) on the long arm of chromosome 12. We have studied two large kindreds from different ethnic backgrounds, segregating an autosomal dominant form of SCA. A total of 207 living individuals, including 50 affected, were examined, and blood was collected. We performed linkage analysis using anonymous DNA markers which flank the two previously described loci. Our results demonstrate that the two kindreds, one Austrian-Canadian and one French-Canadian, are linked to SCA-2 (chromosome 12q). Multipoint linkage analysis places the SCA-2 locus within a region of approximately 16 cM between the microsatellites D12S58 and D12S84/D12S105 (odds ratio 2,371:1 in favor of this position). We show that the SCA-2 locus is not a private gene and represents an alternative SCA locus.

Austria↗

PubMed1993

Atrophy of mesial structures in patients with temporal lobe epilepsy: cause or consequence of repeated seizures?

We studied 70 epileptic patients by using magnetic resonance imaging volumetric measurements of amygdala (AM) and hippocampal formation (HF). Fifty patients presented with intractable temporal lobe epilepsy (TLE), 10 patients had focal extratemporal lobe epilepsy, and 10 had generalized epilepsy. In 91% of the 45 TLE patients without foreign tissue lesions, there was significant smallness of the AM and/or HF coinciding with the side of electroencephalographic seizure onset. No significant smallness or asymmetry was demonstrated in patients with focal extratemporal or generalized epilepsy. We performed a linear regression analysis, plotting the number of years of recurrent seizures and the estimated seizure frequency against the volumes of the AM and HF. There was no correlation between either of these two parameters and AM or HF volume (p > 0.9). There was also no correlation between the patient's age and volumetric measurements of AM or HF, nor did these measurements correlate with the occurrence of generalized seizures. On the other hand, patients with antecedent prolonged febrile convulsions in early childhood had significantly smaller AM and HF, compared with those without such a history (p < 0.001). The findings indicate that repeated seizures or longer duration of epilepsy do not cause increased atrophy of AM or HF that is measurable by volumetric magnetic resonance imaging.

Adolescent↗

PubMed1993

MRI volumetric measurement of amygdala and hippocampus in temporal lobe epilepsy.

We performed MRI volumetric measurements of the amygdala (AM), the hippocampal formation (HF), and the anterior temporal lobe in a group of 30 patients with intractable temporal lobe epilepsy (TLE) and in seven patients with extratemporal lobe foci. Measurements were analyzed with a semiautomated software program and the results compared with those of normal controls and correlated with the findings of all other investigations. In particular, we compared the results with the lateralization of epileptic abnormalities in the EEG. Volumetric studies of AM and HF showed lateralization of measurable atrophy consistent with that derived from extracranial and intracranial EEG examinations. The HF volumes were more sensitive and provided a lateralization in 87%. Combined measurements of AM and HF showed lateralization in 93%, always congruent with the results of EEG lateralization. This slight but important additional improvement in discrimination justifies using AM measurements in MRI volumetric studies of mesial temporal structures. Volumetric studies combined with other currently employed noninvasive techniques may diminish the need for invasive methods of investigation in patients with TLE.

Adult↗

PubMed1993

Early childhood prolonged febrile convulsions, atrophy and sclerosis of mesial structures, and temporal lobe epilepsy: an MRI volumetric study.

We performed MRI volumetric measurements of the amygdala (AM) and hippocampal formation (HF) in a group of 43 patients with temporal lobe epilepsy not controlled by optimal drug treatment. Fifteen patients (35%) had a history of prolonged febrile convulsions (PFC) in early childhood; 30 patients underwent surgery, and histopathology was available in twenty-four. The mean values of AM and HF volumes ipsilateral to the EEG focus were significantly smaller than those of normal controls. The volumetric measurements showed a more pronounced atrophy of the AM in patients with a history of PFC, although the HF volumes were also smaller in this group. Patients with a history of PFC had a higher proportion of more severe mesial temporal sclerosis (MTS) compared with those with no PFC. These findings confirm a correlation between early childhood PFC, the severity of atrophy of mesial structures, and MTS.

Adolescent↗

PubMedDate not supplied

Study of three intragenic polymorphisms in the Machado-Joseph disease gene (MJD1) in relation to genetic instability of the (CAG)n tract.

Intergenerational instability is one of the most important features of the disease-associated trinucleotide expansions, leading to variation in size of the repeat among and within families, which manifests as variable age at onset and severity, and is probably the basis for the occurrence of anticipation. Several factors are known to affect the degree of instability, namely the type of repeated sequence, its initial size, the presence or absence of interruptions in the repetitive tract and the gender of the transmitting parent. A recent study demonstrated the effect of an intragenic polymorphism (C987GG/G987GG) in the Machado-Joseph disease causative gene, immediately downstream of the CAG repeat, on the intergenerational instability of the expanded repeat. Surprisingly, there was an effect not only of the specific allele in cis to the disease chromosome, but also of the allele on the normal chromosome, suggesting the existence of an interaction between the normal and expanded alleles that affects the fidelity of replication of the (CAG)n tract. This effect could be a direct effect of the polymorphism studied or, alternatively, this polymorphism could be in disequilibrium with some other flanking sequence which affects the instability of the repetitive (CAG)n tract. In order to confirm the previous results in a different population and to distinguish between a direct and indirect effect of the CGG/GGG polymorphism, we typed 70 parent-progeny pairs for which the variation in the (CAG)n length in the MJD1 gene was known, for three intragenic polymorphisms: C987GG/G987GG and two additional, newly described ones, TAA1118/TAC1118 and A669TG/G669TG. We also typed a control population of 125 individuals for the A669TG/G669TG, C987GG/G987GG and TAA1118/TAC1118 polymorphisms, in an attempt to identify any association between haplotype and (CAG)n length in normal chromosomes, suggestive of an instability-predisposing effect of the repeat-flanking sequences, which could have led to the origin of the MJD mutation in the human population. We confirmed the effect of the C987GG/G987GG polymorphism on intergenerational instability when present in trans. Our results suggest that this effect is restricted to a small region of the gene, immediately downstream of the CAG repeat, which includes this particular nucleotide substitution and the stop codon of the MJD1 cDNA, and is not a more widespread chromosomal effect. The lack of a significant association of any specific intragenic haplotype with larger CAG repeats in normal chromosomes, together with the absence of an effect of the intragenic haplotype in cis on the intergenerational instability of the expanded (CAG)n in MJD families does not indicate the existence of an instability-predisposing haplotype.

Alleles↗