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Biomedical subjects

M Spadaro

Publications and source records attributed to M Spadaro.

At least 19 recordsLinked to original sources
PubMed1996

Pre-symptomatic neurological involvement in Behcet's disease: the diagnostic role of magnetic transcranial stimulation.

Twenty Behcet's disease (BD) patients with or without neurologic signs and symptoms were studied by means of magnetic transcranial stimulation. The most frequent abnormalities were an increase of motor evoked potential latency and a delay of central motor conduction time (CMCT). In 5 out of 9 BD patients with pyramidal signs central motor conduction changes were present. Furthermore, 2 out of 7 patients without neurologic signs and symptoms showed an increased threshold and a prolonged CMCT. The data obtained suggest that this technique is useful not only to confirm the neurologic impairment but also to reveal subclinical or pre-symptomatic central motor involvement in BD subjects.

Adolescent↗
PubMed1994

The trinucleotide repeat expansion on chromosome 6p (SCA1) in autosomal dominant cerebellar ataxias.

Affected members of 73 families with a variety of autosomal dominant late onset cerebellar ataxias (ADCAs) were investigated for the trinucleotide (CAG) repeat expansion which is found in pedigrees exhibiting linkage to the SCA1 locus on chromosome 6. Most of the families were too small for linkage analysis. The mutation was only found in ADCA type I, in 19 out of 38 such kindreds investigated (50%). It was slightly more common in Italian (59%) than British (50%) families, and was also found in Malaysian, Bangladeshi and Jamaican kindreds. Overall, ADCA type I patients with the expansion had a lower incidence of hyporeflexia and facial fasciculation than those without. The trinucleotide expansion was not found in eight families with ADCA and maculopathy or 24 kindreds with a pure type of ADCA, confirming that these syndromes are genetically distinct. It was also not detected in 12 patients with sporadic degenerative ataxias. DNA analysis for the SCA1 mutation is useful diagnostically in single patients or small families, and can be used for presymptomatic testing where appropriate.

Adolescent↗
PubMed1994

Effect of trinucleotide repeat length and parental sex on phenotypic variation in spinocerebellar ataxia I.

Trinucleotide repeat expansion has been found in 64 subjects from 19 families: 57 patients with SCA1 and 7 subjects predicted, by haplotype analysis, to carry the mutation. Comparison with a large set of normal chromosomes shows two distinct distributions, with a much wider variation among expanded chromosomes. The sex of transmitting parent plays a major role in the size distribution of expanded alleles, those with > 54 repeats being transmitted by affected fathers exclusively. Our data suggest that alleles with > 54 repeats have a reduced chance of survival; these appear to be replaced in each generation by further expansion of alleles in the low- to medium-expanded repeat range, preferentially in male transmissions. Detailed clinical follow-up of a subset of our patients demonstrates significant relationships between increasing repeat number on expanded chromosomes and earlier age at onset, faster progression of the disease, and earlier age at death.

Adult↗
PubMed1993

Predictive value of neurological abnormalities in HIV 1 patients in the early stages of the infection.

A longitudinal clinical neurological and electrophysiological follow-up study was carried out on 31 HIV1 seropositive outpatients in the asymptomatic or LAS stages of the infection (CDC II-III). The results of clinical examination and multimodal evoked potentials (EP) recording showed a high percentage of abnormalities (42% and 39% of cases respectively); in a statistically significant number of subjects these abnormalities were predictive of subsequent immunological deterioration, thus demonstrating the close relationship between neurological and immunological functions in HIV1 infection.

Adult↗
PubMed1993

Clinical study of large kindreds with autosomal dominant HLA-linked spinocerebellar ataxia (SCA1) of late onset.

Six families with SCA1 were studied. The clinical data on 35 patients are reported. Cerebellar and pyramidal system involvement was invariably found in association with brainstem, spinal cord and/or peripheral nervous system disorders. In our patients the clinical features appeared concordant when the patients with the same disease duration were compared. Previous reports of SCA1 families had shown great variability in clinical phenotype both interfamilial and intrafamilial. We suggest that the phenotype might appear more homogeneous if disease duration is taken into account.

Adolescent↗
PubMed1993

Myopathy in long-term AZT therapy: clinical, electrophysiological and biopsy study in 67 HIV+ subjects.

The occurrence of muscular pathologies in AZT treated subjects has been evaluated in 67 HIV seropositive outpatients (56 AZT-treated and 11 untreated controls) in a neurological clinical and paraclinical follow-up study. Standard electromyographic and electrodiagnostic examinations, together with muscle enzyme determination, were performed in every subject, and periodically repeated at fixed intervals; in 11 patients a muscle biopsy sample was also obtained. An AZT-related myopathy was diagnosed in 8 biopsied cases; 9 more patients were considered to have AZT myopathy on clinical, EMG and ex juvantibus criteria. Statistical analysis showed that treatment duration was more relevant to the development of the myopathy than AZT dosage, though an individual predisposition could not be excluded, at least in a small number of cases. The risk of developing a toxic myopathy will therefore have to be considered when evaluating long-term effects of AZT therapy.

Adult↗
PubMed1993

The gene for spinal cerebellar ataxia 1 (SCA1) is flanked by two closely linked highly polymorphic microsatellite loci.

The gene for one form of autosomal dominant spinal cerebellar ataxia (SCA1), is mapped by linkage to chromosome 6p, very close to the microsatellite locus D6S89. Eight large Italian kindreds segregating SCA1, as defined by very close linkage to D6S89, were genotyped with five microsatellite markers linked closely to D6S89, all mapping within a 6 cM interval on 6p. Multipoint linkage analysis and haplotypes from recombinants map SCA1 between two of these markers, D6S274 and D6S259, 5-6 cM apart. A single rare four marker haplotype within this interval shows linkage disequilibrium with the disease locus in southern Italy and is transmitted with SCA1 in five kindreds originating from this area.

Alleles↗
PubMed1993

Ultrastructural sperm abnormalities and cerebellar atrophy: does a correlation exist? Report of two cases without endocrine hypogonadism.

Spermiograms were performed in two young patients with cerebellar ataxia, one familial and the other sporadic. The subjects did not have endocrine abnormalities, but there was MRI evidence of cerebellar atrophy. Light and electron microscope examination revealed sperm abnormalities similar to those described in Purkinje cell degeneration (PCD). PCD is an autosomal recessive mutation observed only in the mouse, characterized by mild ataxia due to the postnatal degeneration of cerebellar Purkinje cells and male sterility due to morphological sperm abnormalities.

Adult↗
PubMed1993

Electrophysiological study (VEP, BAEP) in HIV-1 seropositive patients with and without AIDS.

One hundred-twenty nine HIV-1 seropositive patients (39 females, 90 males) were studied by means of pattern visual evoked potential (VEP) and brainstem auditory evoked potential (BAEP) recording. Utilizing the criteria of the Centers for Disease Control the patients were clinically defined and then subdivided into four groups: group A included patients of category II (n:11); group B patients of category III (n:29); group C patients of category IVa and IVc2 (n:55) and group D patients belonging to the other subgroups of category IV (n:34). EP were altered in 26.35% of the entire group with a marked prevalence of BAEP alterations (21.7%) rather than of VEP (4.65%). A considerable amount of BAEP abnormalities (24.13%) were found in patients with persistent generalized lymphadenopathy (group B). A significant increase of BAEP mean interpeak latencies were observed in group B, C, D patients when compared with those of the control group. On the whole, EP were altered in 20.65% of the neurologically asymptomatic patients. EP alterations may precede any clinical manifestation and can be found during the earlier phases of HIV-1 infection.

AIDS-Related Complex↗
PubMed1992

AZT-induced mitochondrial myopathy.

Histochemical, electron microscopy and biochemical studies were performed on muscle biopsy specimens from 11 AIDS patients treated with zidovudine. A peculiar association of structural abnormalities and mitochondrial dysfunction was found. Focal cytochrome c oxidase (COX) deficiency was evident in muscle sections from 9 patients, 8 of whom had received long-term treatment while one had been treated for 1 month only. Electron microscopy showed changes in number, size and structure of mitochondria. Biochemical studies proved partial COX and succinate cytochrome c reductase (SCR) deficiency in 4 patients; one patient had only reduced SCR activity. Our data confirm that AZT therapy can cause toxic myopathy with mitochondrial dysfunction.

Adult↗
PubMed1992

Autosomal dominant pure cerebellar ataxia. Neurological and genetic study.

A family with late-onset autosomal dominant pure cerebellar ataxia was studied both neurologically and genetically. Neuroimaging and electrophysiological results were in agreement with the clinical evidence showing involvement of the cerebellar system only, even many years after onset. No atrophy of inferior olives was observed by magnetic resonance imaging, while cerebellar atrophy was extremely marked. A very slow disease progression was observed in all patients. The disease can be differentiated from autosomal dominant olivo-ponto-cerebellar atrophies, and in particular from spinocerebellar ataxia type 1 mapping on chromosome 6p, which shows an early multisystemic involvement and a more rapid progression toward inability. A genetic study of the family with the 6p DNA marker D6S89 closely linked to the spinocerebellar ataxia type 1 locus was performed. Results showed significant exclusion of a linkage between the disease and the marker within a distance of 8.5% recombination, indicating that genetic heterogeneity underlies phenotypic differences.

Adult↗
PubMed1992

HLA-linked spinocerebellar ataxia: a clinical and genetic study of large Italian kindreds.

Five families with late onset autosomal dominant spinocerebellar ataxia, were studied. Linkage between the disease and HLA loci on the short arm of chromosome 6 was shown in the two largest pedigrees. Clinical study of 26 patients and neuropathological study in one are reported. The disease was characterized by cerebellar and pyramidal involvement variably associated with cranial nerve and peripheral nervous system disorders. A remarkable concordance of the main clinical features was observed in patients with similar disease duration. Comparison with previous reports of HLA-linked spinocerebellar ataxia kindreds showed differences in clinical phenotypes. Although these might be due to genetic variation, the hypothesis is suggested that the phenotype might appear more homogeneous if disease duration is taken into account.

Adult↗
PubMed1991

Association of "top of the basilar" syndrome with megadolichobasilar artery. Clinical and neuroimaging evaluation.

We describe the case of a patient with a history of trigeminal neuralgia who suddenly developed the "top of the basilar" syndrome. MRI disclosed ischemic lesions in the left paramedian mesencephalic tectum, in the left ventral thalamus, in the left occipital lobe and a megadolichobasilar artery (MDBA). The association of MDBA with the top of the basilar syndrome is rarely reported. We discuss the possible hemodynamic mechanism producing a top of the basilar syndrome in the presence of MDBA.

Aged↗
PubMed1991

Spinocerebellar ataxia (SCA1) in two large Italian kindreds: evidence in favour of a locus position distal to GLO1 and the HLA cluster.

Two large Italian pedigrees with HLA-linked spinocerebellar ataxia (SCA1) were typed for HLA-A, -B and -DR as well as for markers either distal (F13A, D6S8) or proximal (D6S29, GLO1) to HLA. Pairwise linkage analyses of SCA1 vs. HLA-A, -B, and -DR showed peak lodscores of 5.3, 5.6 and 3.3 respectively at 7% recombination. Negative lodscores significantly excluded linkage with F13A at less than 5% and with GLO1 at less than 10%. The lodscores with D6S8 and D6S29 had only low peaks. Recombination events in the two pedigrees and the estimated genetic distances of SCA1 from GLO1 and HLA favour the hypothesis of a SCA1 location distal to both of them. An order cen-GLO1-HLA-SCA1-tel appears therefore most likely with present data. These results are discussed in relation to previous reports placing SCA1 distal to HLA in two families and

Adult↗
PubMed1991

The gene for autosomal dominant spinocerebellar ataxia (SCA1) maps telomeric to the HLA complex and is closely linked to the D6S89 locus in three large kindreds.

We studied three large kindreds with the HLA-linked form of spinocerebellar ataxia (SCA1) in order to localize the SCA1 locus on the short arm of chromosome 6 (6p). Two loci containing highly informative dinucleotide repeat sequences were used for linkage analysis. These two loci are D6S89, which is telomeric to the HLA region, and T complex-associated testes-expressed 1 (TCTE1), centromeric to HLA. Pairwise linkage analysis of SCA1 and D6S89 revealed a maximum lod score of 5.86 in the Houston SCA1 (HSCA1) kindred and of 8.08 in the Calabrian SCA1 (SCA1) kindreds, at recombination fractions of .050 and .022, respectively. A maximum pairwise lod score of 4.54 at a recombination frequency of .100 was obtained for SCA1 and TCTE1 in the HSCA1 kindred. No evidence for linkage was detected between TCTE1 and SCA1 in the CSCA1 kindreds. Multilocus linkage analysis of SCA1, HLA, and D6S89 in all three kindreds provided strong evidence for localization of the SCA1 locus telomeric to the HLA regions. However, multilocus linkage analysis of SCA1, HLA, and TCTE1 with HSCA1 family genotypes indicated the possibility of a location of the SCA1 locus centromeric to HLA. An analysis of HSCA1 recombinants in this region of chromosome 6 revealed relatively high recombination frequencies between HLA and each of the other two markers and relatively low frequencies between the latter and SCA1, predicting that the SCA1 locus would tend to segregate away from HLA together with D6S89 or TCTE1, as found with the three-point linkage analyses for this family.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗