Amyotrophic lateral sclerosis in Sardinia (Italy): epidemiologic features from 1957 to 2000.

OBJECTIVES: To evaluate epidemiological variables of amyotrophic lateral sclerosis (ALS) in Sardinia (Italy) in the 1991-2000 periods and compare them with the preceding decades. MATERIAL AND METHODS: Survey, critical reappraisal or clinical re-evaluation of all ALS cases with onset in the decade 1991-2000; calculation of crude and age-adjusted incidence, duration of disease, survival rates and the latency between onset of symptoms and diagnosis. RESULTS: A significant increase in the mean annual incidence was observed in comparison with the values found in the two previous decades, 1971-1980 and 1981-1990. The distribution of the disease in various areas of the island was found to be not at all homogeneous. No significant modifications of the duration of the disease and survival rates were observed. CONCLUSION: The role of particular exogenous factors, albeit still unclear, can be invoked.

Evidence of early childhood as the susceptibility period in multiple sclerosis: space-time cluster analysis in a Sardinian population.

The authors analyzed the natural history of multiple sclerosis (MS) before onset to identify the period of susceptibility and exogenous factors that might play a role in causing the disease. Space-time cluster analysis was performed among northern Sardinians, a genetically stable Italian population that showed an increasing risk of MS between 1965 and 1999. Residence changes from birth to clinical onset were recorded for all MS patients with clinical onset between 1965 and 1999 in the province of Sassari. Closeness in space and time was defined as living in the same municipality and differing in year of birth by 1, 2, or 5 years. Analyses were performed for the period from birth to age 25 years or MS onset and in demographic and clinical subgroups. Clustering was substantial in early childhood. Clustering was most marked in the most recent cases, among women, and among patients with early age at onset, a relapsing-remitting course, and in the eastern subarea. No clustering was found when closeness in time was defined as a fixed number of years before onset, which argues against a fixed latency period. Early childhood seemed to be a period of increased susceptibility to MS. This evidence and the increasing incidence of MS in northern Sardinia are compatible with a change in environmental exposure.

The C-->G transition in the alpha 2-globin gene of a normal alpha alpha-chromosome is responsible for the Hb G-Philadelphia variant in Sardinians.

Sequencing of alpha-globin genes of 18 Sardinian heterozygotes for the Hb G-Philadelphia [alpha 68(E17)Asn-->Lys] variant, with four active alpha genes and circulating level of the variant of about 27%, showed the AAC-->AAG change at codon 68 of the alpha 2-globin gene (alpha(G)alpha/alpha alpha). Two heterozygotes with level of about 37% were the carriers of the same mutation on the same alpha 2 gene, and of the alpha 2 alpha 1 hybrid gene, because of the 3.7-kb deletion, in trans (alpha(G)alpha/-alpha(3.7)). In Black people, the same C-->G mutation occurs on the hybrid gene (-alpha(G)3.7), whereas in Caucasians the Lys for Asn change is because of the C-->A transversion occurring on the alpha 2 gene of a normal alpha alpha arrangement. The identification of the C-->G mutation on the normal alpha alpha chromosome points to an undescribed genotype for this rather common variant, which is probably because of the high rate of recombination between the duplicated alpha-globin genes.

A real-time classification system of thalassemic pathologies based on artificial neural networks.

Thalassemias are pathologies that derive from genetic defects of the globin genes. The most common defects among the population affect the genes that are involved in the synthesis of alpha and beta chains. The main aspects of these pathologies are well explained from a biochemical and genetic point of view. The diagnosis is fundamentally based on hematologic and genetic tests. A genetic analysis is particularly important to determine the carriers of alpha-thalassemia, whose identification by means of the hematologic parameters is more difficult in comparison with heterozygotes for alpha-thalassemia. This work investigates the use of artificial neural networks (ANNs) for the classification of thalassemic pathologies using the hematologic parameters resulting from hemochromocytometric analysis only. Different combinations of ANNs are reported, which allow thalassemia carriers to be discriminated from normals with 94% classification accuracy, 92% sensitivity, and 95% specificity. On the basis of these results, an automated system that allows real-time support for diagnoses is proposed. The automated system interfaces a hemochromo analyzer to a simple PC.

Multiple sclerosis epidemiology in Sardinia: evidence for a true increasing risk.

OBJECTIVES: To update prevalence and incidence rates of MS among Sardinians. MATERIALS AND METHODS: The present work is a "spider" kind of population based survey, conducted over the interval 1968-97, on patients with MS (Poser criteria) living in the province of Sassari, Northern Sardinia (454,904 population). RESULTS: A crude total prevalence rate of 144.4 per 100,000, an onset-adjusted prevalence rate of 149.7 per 100,000 and an average annual incidence rate of 8.2 for the period 1993-7 were found. CONCLUSION: Repeated epidemiological assessments of MS in Sardinia over decades have shown that the island is at high risk for MS. The present work highlights that MS incidence in Sardinia has been increasing over time. Although a substantial and widely spread improvement in MS case ascertainment can be postulated as the reason for such observations, a comparison between our data and those recently reported from a more industrialized province in Northern Italy seems to prove an at least partially real increase in MS risk among Sardinians and favours the hypothesis of a MS "Sardinian focus" as related to its latitude.

Epidemiology of myasthenia gravis in northwestern Sardinia.

A previous epidemiological study on myasthenia gravis (MG) in Sardinia indicated a prevalence rate of 4.5 per 100,000 population and an incidence of 0.25 per 100,000 population in the period 1958-1986. This study, however, investigated the entire Sardinian population (about 1,500,000) and the reported rates are likely to be underestimated. Because the use of a very large population has been found to cause major bias in case finding, the present study was designed to overcome this bias by determining the prevalence and incidence of MG in a well-defined area of Northwestern Sardinia, with a population of about 270,000 (1991 census). Potential MG cases were ascertained using all possible medical sources. The diagnosis of MG was based on the clinical, neurophysiological and conventional pharmacological findings (Tensilon test, response to anticholinesterases). On prevalence day (December 31, 1994) 29 MG patients were living in the study area (17 women and 12 men). Since the total population on prevalence day was 268,926 (137,284 women and 131,642 men), the calculated prevalence was 11.1 per 100,000 population (12.4 women and 9.9 men). The present study shows that the risk of MG in Sardinia is higher than previously suggested. The risk, however, is not significantly different from that found in other comparable Italian and European areas. It contrasts with what has been found for other autoimmune diseases such as multiple sclerosis and insulin-dependent diabetes mellitus in Sardinians, both showing frequencies up to 3-5 times higher than in the rest of Italy.

Epidemiology of multiple sclerosis in Northwestern Sardinia: further evidence for higher frequency in Sardinians compared to other Italians.

The Sardinians are an ethnically homogeneous population, having a genetic structure quite different from that of all other Italian and European populations. All epidemiological studies carried out in Sardinia since 1975 indicate that this Mediterranean island shows twice the prevalence of multiple sclerosis (MS) compared to continental Italy, but the size of the Sardinian communities so far surveyed has been too small to draw definitive conclusions. To overcome this draw-back, we have studied the frequency of MS in a well-defined area of north-western Sardinia, with a population of about 270,000 in the 1991 census. Based on 276 MS cases, the prevalence on December 31st, 1991, was 102.6 per 100,000. The incidence, averaging 2 per 100,000 in the period of 1962 to 1971, rose to 5 in the period from 1977 to 1991. The present study confirms the higher frequency of MS among Sardinians compared to other Italian populations. Genetic, linguistic and historical data suggest a role of environmental and genetic factors in determining the notable difference in MS risk between Sardinia and the rest of Italy.

Amyotrophic lateral sclerosis in Sardinia, Italy: an epidemiologic study.

The authors carried out an epidemiologic study on amyotrophic lateral sclerosis in Sardinia for the years 1957 through 1990. The duration of the disease and survival were significantly shorter in bulbar form. The distribution of ALS in various areas of the island was found to be not at all homogeneous. Mean yearly incidence showed no significant variations in the decades 1971-80 and 1981-90. In the last decade, an increase of bulbar forms was observed.

Upbeat nystagmus as an early sign of cerebellar astrocytoma.

A boy with a left-hemispheric cerebellar astrocytoma had upbeat nystagmus exhibiting increasing-velocity slow phases. The nystagmus improved after excision of the tumour.

Incidence of multiple sclerosis in the town of Sassari, Sardinia, 1965 to 1985: evidence for increasing occurrence of the disease.

Prevalence studies carried out in Sardinia from 1975 suggest an increasing occurrence of MS. However, it is questionable whether this increase represents a real change in MS incidence or simply reflects longer survival. Data from 79 patients indicated the average annual incidence for the period 1965 through 1985 was 3.4 per 100,000. On December 31, 1985, the prevalence rate was 69 per 100,000. Evaluation of MS temporal trends showed a significant increase in MS incidence during the study period: values ranged around two per 100,000 in the triennial periods 1965-1967, 1968-1970, and 1971-1973, and around five in each triennium from 1977 onward.

Sardinia, a high-risk area for multiple sclerosis: a prevalence and incidence study in the district of Alghero.

Findings from small descriptive studies carried out in the last few years in Sardinia suggest that this region is now of high rather than medium risk for multiple sclerosis. It is uncertain whether this high prevalence reflects a different approach in case finding over time or a true change in disease occurrence. We report the results of a prevalence and incidence survey conducted in the district of Alghero, a community of 78,000 people in northwest Sardinia. Based on data from 31 patients, the average annual incidence for the period 1971 through 1980 was 4.1 per 100,000. On December 31, 1980, the prevalence rate was 59 per 100,000. The results support the view that Sardinia is now a high-risk area for multiple sclerosis, and further suggest a rise in the occurrence of the disease in recent years.

Incidence of multiple sclerosis in Macomer, Sardinia, 1912-1981: onset of the disease after 1950.

Intensive search of all cases of MS occurring in the Sardinian commune of Macomer since 1912 indicated that MS was absent up to the early 1950s. All 13 ascertained cases had clinical onset in the years 1952-1981. During this period, the average annual incidence was 4.8 per 100,000; the highest incidence was found in the period 1957-1961, slowly decreasing up to 1981. MS was probably introduced after 1945, when the centuries-old isolation of Macomer ended and the native population came into contact with individuals from high- and medium-risk areas.

Determination of glycosylated haemoglobin by isoelectric focusing in non-linear pH gradients.

A new isoelectric focusing technique for the separation and quantitation of glycosylated haemoglobin (HbA1c) is described. By using an equimolar mixture of two separators (0.2 M beta-alanine + 0.2 M 6-aminocaproic acid) a 2-pH unit Ampholine range (pH 6-8) is transformed in a shallow, 0.6-pH unit span (pH 6.7-7.3). This brings about an increment of resolution between HbA and HbA1c by a factor of about three, thus allowing proper densitometric evaluation of the trichloroacetic acid-fixed MetHb bands by conventional gel scanners. Excellent agreement is found among microchromatography, isoelectric focusing followed by densitometry in situ, and isoelectric focusing followed by band excision, elution and spectrophotometric determination. The present method also allows full resolution between HbA1c and fetal haemoglobins (F and Fac bands).

Neonatal screening of beta-thalassemias by thin layer isoelectric focusing.

As an alternative to the recently proposed screening for beta-thalassemias by isoelectric focusing (IEF) of denatured globin chains in urea-detergent gels [6], IEF of intact hemoglobins, obtained from umbilical cord blood in neonatal units, is reported here. For maximum separation, IEF should be performed in nonlinear pH gradients, in gels containing 0.2 M beta-alanine and 0.2 M 6-amino caproic acid, which flatten the pH gradient around pH 7, thus increasing the resolution between HbA and HbFac. The method can unambiguously detect homozygous and heterozygous beta-thalassemic conditions. A bimodal distribution of HbA at birth has been found: In heterozygous patients, HbA values of 9.02% (range 6.8-9.98%) have been found while in normal newborns HbA levels of 20.34% (range 11.02-30.6%) have been demonstrated.