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Biomedical subjects

P Valentino

Publications and source records attributed to P Valentino.

At least 19 recordsLinked to original sources
PubMed2007

Investigating the role of brain-derived neurotrophic factor in relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) is a common, heterogeneous disorder of the central nervous system with a complex trait composed of both genetic and environmental factors. Recently, scientific interest has increased in defining factors that possibly contribute to brain functional plasticity; the results might be useful to assess the relationship between MS lesion burden and clinical events, as well as explaining the well-known phenotypic heterogeneity of the disease. In this study, we explored the effect of the Val66Met brain-derived neurotrophic factor (BDNF) functional polymorphism on cognitive performances and volumetric measurements obtained by magnetic resonance imaging of the brain in a selected population of relapsing-remitting MS (RRMS) patients, with relatively short disease duration and minimal clinical disability, compared to gender, age and educational-level matched healthy subjects. We found that in the RRMS group, the BDNF Met-allele was significantly associated with the lower volume of cerebral grey matter (GM) (P = 0.005). Furthermore, a significant (P = 0.013) interaction effect between 'MS-status' and the BDNF genotype was found for GM volumes, with the result that patients carrying the BDNF Met-allele showed a higher risk of developing global GM atrophy than the homozygous Val/Val. No BDNF-related impact on global neuropsychological functions resulted in either RRMS patients or controls. Our data seem to be consistent with the reported influence of BDNF in neuronal plasticity, thus suggesting that the Met-allele might have a negative prognostic effect on cortical morphometry in RRMS patients.

Adolescent↗
PubMed2006

Genetic variation in the myeloperoxidase gene and cognitive impairment in multiple sclerosis.

There is evidence that multiple sclerosis (MS) may associated with cognitive impairment in 25 to 40% of cases. The gene encoding myeloperoxidase (MPO) is involved in molecular pathways leading to beta-amyloid deposition. We investigated a functional biallelic (G/A) polymorphism in the promoter region (-463) of the MPO gene in 465 patients affected by MS, divided into 204 cognitively normal and 261 impaired. We did not find significant differences in allele or genotype distributions between impaired and preserved MS patients. Our findings suggest that MPO polymorphism is not a risk factor for cognitive impairment in MS.

Alleles↗
PubMed2006

Treatment of multiple sclerosis with interferon beta in clinical practice: 2-year follow-up data from the South Italy Mobile MRI Project.

This follow-up study assessed the 2-year clinical and magnetic resonance imaging (MRI) outcomes of patients with multiple sclerosis (MS) originally enrolled in an MRI study conducted at eight centres in south Italy (the South Italy Mobile MRI Project). Of the 597 MS patients recruited at baseline, 391 returned for the follow-up study. Of these, 363 provided 2-year clinical and MRI follow-up data, and 215 were still undergoing treatment with one of four interferon beta regimens: Avonex, 30 mcg intramuscularly once weekly; Betaferon, 250 mcg subcutaneously (sc) every other day; Rebif 22 mcg sc three times weekly (tiw; Rebif 22); or Rebif 44 mcg sc tiw (Rebif 44). Over the 2-year follow-up period, patients receiving the higher dose of Rebif were more likely to remain free from relapses [odds ratio (OR) = 2.23] and from developing both new T2 (OR = 0.15) and new T1 black hole lesions (OR = 0.22), when compared with patients in the Avonex group. Despite some limitations in the trial design, the results from this follow-up study provide helpful clinical and MRI data on the efficacy of interferon beta regimens in MS patients treated in the clinical setting.

Analysis of Variance↗
PubMed2006

Cognitive dysfunction in patients with relapsing-remitting multiple sclerosis.

Cognitive dysfunction is considered one of the clinical markers of multiple sclerosis (MS). However, in the literature there are inconsistent reports on the prevalence of cognitive dysfunction, and separate data for the relapsing-remitting (RR) type of the disease are not always presented. In this study, we submitted 461 RRMS patients to a battery of neuropsychological tests to investigate their impairment in various cognitive domains. As a consequence of the exclusion criteria, the sample is not fully representative of the entire population of RRMS patients. In this selected sample, when only the eight scores of a core battery (Mental Deterioration Battery) were considered (with respective cutoffs), it emerged that 31% of the patients were affected by some degree of cognitive deficit. In particular, 15% had mild, 11.2% moderate and 4.8% had severe impairment. Information processing speed was the most frequently impaired area, followed by memory. When two other tests (SDMT and MCST) were added and cognitive domains were considered, it emerged that 39.3% of the patients were impaired in two or more domains. When four subgroups were obtained by means of cluster analysis and then compared, it emerged that information processing speed and memory deficits differentiated the still cognitively unimpaired from the mildly impaired MS patients. Significant associations were found between cognitive and clinical characteristics. However, due to the large sample size, clinically irrelevant relationships may also have emerged. Even with the limitations imposed by the sample selection and the possible underestimation of the prevalence and severity of cognitive dysfunction, these results seem to provide further evidence that information processing speed deficit may be an early and important marker of cognitive impairment in MS patients.

Adult↗
PubMed2005

Brain atrophy and lesion load in a large population of patients with multiple sclerosis.

OBJECTIVE: To measure white matter (WM) and gray matter (GM) atrophy and lesion load in a large population of patients with multiple sclerosis (MS) using a fully automated, operator-independent, multiparametric segmentation method. METHODS: The study population consisted of 597 patients with MS and 104 control subjects. The MRI parameters were abnormal WM fraction (AWM-f), global WM-f (gWM-f), and GM fraction (GM-f). RESULTS: Significant differences between patients with MS and control subjects included higher AWM-f and reduced gWM-f and GM-f. MRI data showed significant differences between patients with relapsing-remitting and secondary progressive forms of MS. Significant correlations between MRI parameters and between MRI and clinical data were found. CONCLUSIONS: Patients with multiple sclerosis have significant atrophy of both white matter (WM) and gray matter (GM); secondary progressive patients have significantly more atrophy of both WM and GM than do relapsing-remitting patients and a significantly higher lesion load (abnormal WM fraction); lesion load is related to both WM and even more to GM atrophy; lesion load and WM and GM atrophy are significantly related to Expanded Disability Status Scale score and age at onset (suggesting that the younger the age at disease onset, the worse the lesion load and brain atrophy); and GM atrophy is the most significant MRI variable in determining the final disability.

Adolescent↗
PubMed2004

A novel Notch3 gene mutation not involving a cysteine residue in an Italian family with CADASIL.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebrovascular disease leading to accumulating neurologic deficits and dementia. CADASIL has been linked to nucleotide substitutions and deletions in the Notch3 gene. All the mutations described until now lead to unpaired cysteine residue in the epidermal growth factor-like repeats. The authors report a family with CADASIL carrying a deletion in the Notch3 gene that did not involve a cysteine residue.

Adult↗
PubMed2004

Gene conversion events in adult-onset spinal muscular atrophy.

OBJECTIVE: To investigate the possible occurrence of a conversion event in three patients with adult-onset spinal muscular atrophy (SMA) type IV, which represents the mildest form within the spectrum of the SMA phenotype. MATERIAL AND METHODS: We observed three patients with adult onset SMA and apparent isolated deletion of telomeric survival motor neuron (SMN1) exon 7. To distinguish between a deletion and a sequence conversion event of exon 7, these patients were analyzed in greater detail by a simple PCR-based assay. RESULTS: Analysis by DdeI digestion showed products for both telomeric and centromeric copies of exon 8. These findings indicated a gene conversion event as the site for primer R111 was retained at least in one of two alleles. CONCLUSIONS: These results provide first evidence that a conversion event may be also associated with adult-onset SMA, and further support the notion that a gene conversion event is usually associated with a milder SMA phenotype and a later onset of disease.

Adult↗
PubMed2003

Narrowing of the critical region in autosomal recessive spastic paraplegia linked to the SPG5 locus.

Hereditary spastic paraplegias are neurodegenerative disorders characterized clinically by progressive spasticity of the lower limbs. They are inherited as autosomal dominant, autosomal recessive, and X-linked traits. Four Italian families with autosomal recessive pure spastic paraplegia are reported. We show evidence of linkage to the SPG5 locus on chromosome 8p and our data reduce the candidate interval for SPG5 to the11-cM interval spanned by D8S285 and D8S544. We also report the search for mutations in five genes located in the region and their exclusion as candidates for SPG5.

Adult↗
PubMed2001

Juvenile Huntington's disease presenting as progressive myoclonic epilepsy.

A 9-year-old girl, who had no family history of neurologic diseases in the first-degree relatives, had a 3-year history of progressive myoclonus epilepsy (PME). A thorough laboratory investigation was normal. As two sisters of her paternal grandmother were said to have Huntington's disease (HD), the authors looked for HD and found a CAG repeat expansion of 115 repeats. This diagnosis should be considered in addition to other causes in patients with PME. Moreover, the current case further supports the notion that HD should be considered even when a family history is not obvious.

Child↗
PubMed2001

Cerebral venous thrombosis and isolated intracranial hypertension without papilledema in CDH.

BACKGROUND: There is evidence that patients with chronic daily headache (CDH) may have isolated intracranial hypertension without papilledema (IHWOP). Recent studies have emphasized that isolated IH may be due to cerebral venous thrombosis (CVT). OBJECTIVE: To detect the occurrence of CVT in patients with CDH. METHODS: The authors investigated the occurrence of CVT in 114 consecutive patients with CDH by using MR venography (MRV). A portion of these patients underwent a lumbar puncture (LP) to measure CSF pressure. MRV and LP were also performed in 28 age-matched control subjects. RESULTS: In all the control subjects, both MRV and CSF pressure were normal. One hundred three of the 114 patients with CDH had normal MRV. Twenty-seven (Group 1) of these 103 patients underwent LP, and all of them had normal CSF pressure. Eleven (9.6%) of the 114 patients with CDH had CVT of one or both transverse sinuses. Six of these 11 patients had flowing abnormalities of one transverse sinus (Group 2), whereas the remaining five patients showed involvement of both transverse sinuses (Group 3). The CSF pressure of Group 2 was higher than that of either Group 1 or the control subjects, and one of the six patients showed isolated IHWOP. Patients of Group 3 displayed the highest CSF pressure, and four of five had isolated IHWOP. The headache profiles of patients with CDH and CVT did not differ from those of patients with CDH but normal MRV. CONCLUSIONS: CVT, as detected by MRV, occurred in 9.6% of patients who presented with CDH. Almost half of the patients with CVT had isolated IHWOP. These results suggest that MRV may be a useful tool for selecting patients with CDH who should have LP to exclude isolated IHWOP.

Adult↗
PubMed2001

Clinical and genetic study of a large Charcot-Marie-Tooth type 2A family from southern Italy.

The authors report a large pedigree from southern Italy with Charcot-Marie-Tooth disease type 2A (CMT2A). The clinical picture was uniform and characterized by distal muscular weakness and atrophy in the lower limbs, reduced or absent tendon reflexes mainly in the lower limbs, and mild sensory impairment in the feet. Significant linkage to the CMT2A locus on chromosome 1p35-p36 was detected. Based on informative recombination in affected individuals, the authors mapped the CMT2A gene between D1S160 and D1S170.

Adolescent↗
PubMed2001

Silent celiac disease in patients with childhood localization-related epilepsies.

PURPOSE: To evaluate how many patients with a clinical picture of idiopathic childhood localization-related epilepsies may also have silent celiac disease (CD). This will help determine whether investigation for CD should be restricted to those patients with childhood partial epilepsy with occipital paroxysms (CPEO) or should be extended to all patients with childhood partial epilepsy (CPE) regardless of seizure type and electroencephalographic (EEG) paroxysms. METHODS: The study group consisted of 72 patients (31 girls and 41 boys; mean age, 12.6 +/- 4.28 years; age at onset, 6.4 +/- 3.7 years) who were observed consecutively over a 5-year period and who received an initial diagnosis of idiopathic CPE. A diagnosis of CD was confirmed by using enzyme-linked immunosorbent assay (ELISA) to assess the presence of antigliadin antibodies and the immunofluorescent undirected test to assess the presence of antiendomysium antibodies. RESULTS: Twenty-five patients had CPEO, whereas the remaining 47 had CPE with centrotemporal spikes (CPEC). None of the patients with CPEC had positive antibody tests. Of the 25 patients with CPEO, two (8%) had antiendomysium immunoglobulin (Ig) A antibodies. In both of these patients, the jejunal biopsy showed atrophy of the villi and hyperplasia of the crypts, consistent with a diagnosis of CD. Brain computed tomography (CT) was normal in one of these patients and revealed occipital corticosubcortical calcifications in the other. CONCLUSIONS: Our study indicates that CD screening should be performed routinely only in patients with CPEO.

Age Factors↗
PubMed2000

A new locus for autosomal dominant nocturnal frontal lobe epilepsy maps to chromosome 1.

BACKGROUND: Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is caused by mutations in the alpha4 subunit of the neuronal nicotinic acetylcholine receptor (CHRNA4) gene, mapping on chromosome 20q13.2. A second ADNFLE locus was mapped on chromosome 15q24. OBJECTIVE: To report a new third ADNFLE locus on chromosome 1 in a large Italian family. METHODS: The authors performed a clinical and genetic study in a large, three-generation ADNFLE family from southern Italy, including eight affected individuals and three obligate carriers. RESULTS: The age at onset of seizures was around 9 years of age and all affected individuals manifested nocturnal partial seizures of frontal lobe origin. Interictal awake and sleep EEG recordings showed no definite epileptiform abnormalities in most patients. Ictal video-EEG showed that the attacks were partial seizures with a frontal lobe semiology. Intellectual and neurologic examinations, and brain CT or MRI results were always normal. Carbamazepine was effective in all treated patients. Exclusion mapping of the known loci linked to ADNFLE-ENFL1, and ENFL2, on chromosomes 20q13.2 and 15q24-was performed on the pedigree before starting the genome-wide linkage analysis. The whole genome scan mapping allowed the identification of a new ADNFLE locus spanning the pericentromeric region of chromosome 1. CONCLUSIONS: The authors provided evidence for a third locus associated to autosomal dominant nocturnal frontal lobe epilepsy on chromosome 1. Among the known genes mapping within this critical region, the ss2 subunit of the nicotinic receptor (CHRNB2) represents the most obvious candidate.

Adolescent↗
PubMed2000

Vitamin E deficiency due to chylomicron retention disease in Marinesco-Sjögren syndrome.

We report on 2 brothers (aged 19 and 12 years) with Marinesco-Sjögren syndrome who also had very low serum vitamin E concentrations with an absence of postprandial chylomicrons. The molecular study ruled out ataxia with isolated vitamin E deficiency, abetalipoproteinemia, and hypobetalipoproteinemia. The electron microscopy of the intestinal mucosa was consistent with a chylomicron retention disease. We speculate that both chylomicron retention disease and Marinesco-Sjögren syndrome are related to defects in a gene crucial for the assembly or secretion of the chylomicron particles, leading to very low serum levels of vitamin E.

Adult↗