Nelide Romeo

Two Novel SCN1A Missense Mutations in Generalized Epilepsy with Febrile Seizures Plus

) for muta-tions in SCN1A, SCN1B, and GABRG2 genes (1–3).Probands were ascertained from the clinical practice inthree epilepsy centers in southern Italy. Detailed familypedigrees were constructed, including maternal and pa-ternal lines extending as far back as possible. In the ninefamilies, we investigated 110 members of whom 37 indi-viduals were determined to be affected. Most patients hadfebrile seizures (FSs) or FS plus (FS

APOE and risk of cognitive impairment in multiple sclerosis

Objectives‐ The APOE gene polymorphism and the −491 A/T polymorphism in its regulatory region have been associated with an increased risk for developing Alzheimers disease. We examined these polymorphisms in multiple sclerosis (MS) patients, to determine if a genetic predisposition may explain the risk for developing cognitive decline in MS. Material and methods‐ Eighty‐nine relapsing‐remitting and secondary progressive MS patients underwent to a full neuropsychological battery as well as to determination of APOE and −491 A/T polymorphisms. Genetic analysis was also performed in 107 population controls. Results‐ The APOE polymorphism was not associated with the risk of cognitive impairment in MS patients. The AA genotype of the −491 A/T polymorphism in the APOE regulatory region was more frequent in cognitively impaired than in cognitively preserved MS subjects. Conclusion‐ The AA homozygous state of the −491 AIT polymorphism of the APOE regulatory region is associated with cognitive impairment in patients with MS.

Pulsed methylprednisolone induces a reversible impairment of memory in patients with relapsing-remitting multiple sclerosis.

Objective – Chronic administration of corticosteroids has been reported to selectively impair explicit memory in systemic diseases without central nervous system involvement. Our aim was to verify that a short course of pulsed intravenous methylprednisolone (IVMP) administered for the treatment of a relapse impairs cognitive functions in relapsing‐remitting multiple sclerosis (RRMS) patients and to determine whether this impairment is reversible. Material and methods – Neuropsychological evaluations were made before the start of treatment, and 7 and 60 days after the end of treatment in 14 RRMS patients. The neuropsychological battery was also administered to 12 controls matched for age, sex and years of education. Results – RRMS patients performed worse than the controls at their baseline evaluation for a variety of neuropsychological tasks. IVMP administration induced a selective impairment of explicit memory which completely recovered 60 days after treatment. Conclusions – In RRMS patients, IVMP induces a selective and reversible impairment of explicit memory.

ApoE Epsilon4 allele and disease duration affect verbal learning in mild temporal lobe epilepsy

Summary:  Purpose: To clarify the possible role of other factors including the ApoE ɛ4 allele for memory decline in temporal lobe epilepsy (TLE).

Apolipoprotein E Polymorphisms and the Risk of Nonlesional Temporal Lobe Epilepsy

Summary: Purpose: To evaluate whether the inheritance of the apolipoprotein E (ApoE) ε4 allele is a risk factor for nonlesional temporal lobe epilepsy (TLE), and to determine whether the newly described ‐491 A/T ApoE polymorphism may independently affect the risk of nonlesional TLE.

Association between Synapsin III gene promoter polymorphisms and multiple sclerosis.

Abstract.Although multiple sclerosis (MS) is considered to be an inflammatory demyelinating disease, increasing evidence indicates that it is also an axonal pathology; indeed, studies of experimental allergic encephalitis showed that several neuronal proteins such as synapsins take part in the pathogenesis of the axonal dysfunction.Synapsins are a family of abundant neuron-specific phosphoproteins with crucial roles in synaptogenesis and neuronal plasticity. Distinct genes encode the three different isolated proteins (I, II and III); of interest, the gene of synapsin III (SYN3) is located in the chromosome 22q12-q13, a locus close to one of the candidate susceptibility regions (22q13.1) for MS.In the present study we selected two polymorphisms (g.–631C > G and g.–196A > G) within the SYN3 5’-promoter region because of the protein’s role and genetic location; we analysed the allele and genotype distributions of these polymorphisms in a selected MS population of southern Italy.An inverse association between MS and the g-631C > G polymorphism was found; indeed, the two polymorphisms were in almost complete linkage disequilibrium and the haplotype analysis showed that the C631/A196 haplotype seemed to confer a significant protection against MS.

Alpha-synuclein promoter haplotypes and dementia in Parkinson's disease.

Dementia is a common complication of Parkinsons disease (PD). It correlates significantly with the presence of cortical, limbic or nigral Lewy bodies, mainly constituted of alpha‐synuclein. Mutations of the alpha‐synuclein gene (SNCA) have been linked to rare familial forms of PD, while association studies on the promoter polymorphisms have given conflicting results in sporadic patients. We have performed a case control study to investigate whether genetic variability in the promoter of the alpha‐synuclein gene could predispose to dementia in PD. A total of 114 demented patients and 114 non‐demented patients with sporadic PD were included in the study. Six polymorphic loci (including the Rep1 microsatellite) in the promoter of the SNCA gene were examined. Each marker, taken individually, did not show association to dementia and no significant differences were observed in the inferred haplotype frequencies of demented and non‐demented patients. Our data suggest the lack of involvement of the SNCA promoter in the pathogenesis of dementia in PD. Further studies in other populations are needed to confirm these results.

FRAXE intermediate alleles are associated with Parkinson’s disease

There is evidence that male subjects with a clinical picture of action tremor, Parkinsonism, and cerebellar ataxia may have Fragile X premutations (FRAXA). We analyzed FRAXA and FRAXE triplet repeats in 203 male subjects with Parkinsons disease (PD) and 370 healthy controls. No full mutations or premutations at the FRAXA and FRAXE loci were found in the subjects with PD or in the controls. FRAXA allele distribution was similar in patients and controls. FRAXE intermediate alleles (31-60 repeats CCG) were found in 13 of 203 (6.4%) subjects with PD and in only one of the 370 (0.27%) healthy controls (P < 0.001), thus indicating that these relatively large alleles may be associated with PD.

Association of tau gene polymorphism with Parkinson's disease.

Abstract.We investigated the segregation of the dinucleotide GT repeat polymorphism in the intron between exons 9 and 10 of the tau gene in 300 patients with Parkinson’s disease (PD) and in 197 normal controls. The A3 allele was more frequent in cases than in controls (30% versus 16%, p<0.001), and individuals carrying at least one A3 allele in their genotype had an increased risk of developing PD (odds ratio 2.78, 95% confidence interval 1.81–4.29). No significant differences were found between patients by considering the age at onset and the presence of family history or dementia. Our findings suggest a possible involvement of the tau gene in the pathogenesis of PD.

Fas Antigen and Sporadic Alzheimer’s Disease in Southern Italy: Evaluation of Two Polymorphisms in the TNFRSF6 Gene

Tumor Necrosis Factor Receptor Super Family 6 gene (TNFRSF6), also known as FAS, encodes the Fas antigen, a cell surface receptor mediating cell apoptosis, situated on chromosome 10q located near the region of linkage to sporadic Alzheimer’s disease (sAD). FAS levels have been reported elevated in the brain of AD patients. Due to both positional and pathobiological criteria, the association of the FAS antigen with this pathology is of great interest. We have tested two SNPs in the FAS gene in 223 Italian patients with non-familial AD from Southern Italy (Calabria region) and 211 healthy control subjects. No significant differences in allelic and genotypic distributions were found between cases and controls, or late and early-onset AD patients, thus suggesting that these polymorphisms do not represent an AD risk factor in our population.