No abstract

Multiple sclerosis is an inflammatory disease of the central nervous system that leads to loss of myelin and oligodendrocytes and damage to axons. We show that daily administration (days 8 to 24) of murine ciliary neurotrophic factor (CNTF), a neurotrophic factor that has been described as a survival and differentiation factor for neurons and oligodendrocytes,

Nineteen families with autosomal dominant partial epilepsy were analysed clinically and electrophysiologically in detail. Seventy-one patients were studied as well as 33 non-epileptic at-risk family members. We subdivided the families into those with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) (n = 8), familial temporal lobe epilepsy (n = 7) and autosomal dominant partial epilepsy with variable foci (n = 4). However, the application of this nosology to certain families was difficult in cases of non-specific or conflicting clinical and electrophysiological evidence. This was underscored by the observation by depth electrode recordings in one patient that a so-called ADNFLE may originate in an extrafrontal area. The evolution of familial partial epilepsies, which exhibit great intrafamilial variability, is not always benign. The level of pharmacoresistance may reach 30%, close to that seen in classical cryptogenic partial epilepsies. The familial character of a partial epilepsy may be unrecognized in small families as some affected members may have only EEG abnormalities and are clinically asymptomatic, which reflects incomplete clinical penetrance. In view of the recent discoveries of mutations in the alpha4 nicotinic acetylcholine receptor subunit in a few families with ADNFLE, this genetic study focused on genes encoding nicotinic receptor subunits and a candidate region on chromosome 10q. No mutation was detected in the alpha4 and 012 nicotinic acetylcholine receptor subunits. Positive but not significant lod scores were obtained in four families with markers from the candidate region on chromosome 10q.

We report a clinical and genetic study of a French family among whom febrile convulsions (FC) are associated with subsequent temporal lobe epilepsy (TLE) in the same individual, without magnetic resonance imaging-identifiable hippocampal abnormalities. Linkage analyses excluded the loci FEB1 and FEB2, previously implicated in FC; the GEFS+1 locus responsible for generalized epilepsy with febrile seizures plus; and the locus implicated in lateral temporal lobe epilepsy. After scanning the entire genome, significant lod scores (>3) for markers on 18qter and suggestive lod scores (>2) for markers on 1q25-q31 were obtained. An analysis of the haplotypes at these two loci supported the hypothesis that two genes segregated with the phenotype. All patients shared common haplotypes for both 1q25-q31 and 18qter chromosomes. All but one unaffected at-risk individuals carried only one, or none, of the disease haplotypes. Under the assumption of digenic inheritance, haplotype reconstruction defined a 26 cM interval on chromosome 1 and a 10 cM interval on chromosome 18. This family suggests that the association between FC and TLE may be observed in the absence of hippocampal structural abnormalities and that they may have, in some cases, a common genetic basis.

Febrile seizures (FS) syndromes exhibit major clinical and genetic heterogeneity. We report a clinical and genetic study of three families with simple FS segregating as an autosomal dominant (AD) trait with high penetrance. All affected members presented a homogeneous phenotype of simple FS. The FS ceased before the age of 5 years. Among the 29 affected family members, only one patient presented two afebrile seizures, and none of the others developed concomitant or subsequent epilepsy. The phenotype differs from that previously reported in families presenting FS or generalized epilepsy with febrile seizures plus (GEFS+). After exclusion of already known loci for FS and GEFS+, we performed a genome-wide scan in the largest family. It led to the identification of a new locus on chromosome 6q22-q24 spanning 6.4 cM between D6S1620 and D6S975. For one of the other two families, the trait also segregated with this locus, but linkage studies could not restrict the candidate region further. The absence of linkage in the third family supports genetic heterogeneity of the AD form of pure simple FS. Sequence analysis excluded the implication of five candidate genes [A kinase anchoring protein 18 (AKAP18), syntaxin 7, putative neurotransmitter receptor (PNR), G protein receptor 57 (GPR57) and G protein receptor 58 (GPR58)] in the interval based on function. The locus mapping to 6q22-q24 seems to be the first identified locus responsible for pure simple FS, the most frequent form of FS. Studies are ongoing to identify the gene.

Spinocerebellar ataxia type 5 (SCA5), one of the genetically heterogeneous autosomal dominant cerebellar ataxias, was assigned to chromosome 11 in a single family descending from the grandparents of President Abraham Lincoln. We report a second, apparently unrelated, SCA5 family of French origin. The overall clinical picture was a slowly progressive cerebellar syndrome beginning mostly in the third decade (27+/-10 years, range 14 to 40). MRI showed a marked global cerebellar atrophy similar to SCA6.

No abstract

No abstract