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

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.</br

Familial autoimmune MuSK positive myasthenia gravis

The familial occurrence of autoimmune myasthenia gravis (MG) with anti-acetylcholine receptor antibodies (AChR Ab) has been rarely reported. Different antibody specificity in family members has also been described. To our knowledge, a familial form of MuSK Ab positive MG has never been reported. We studied the HLA allele profile in a family with two sisters affected by MuSK positive MG

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

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

Seeing Justice Done

OBJECTIVE: To determine the diagnostic relevance of myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) in CSF of seronegative cases by retrospectively analyzing consecutive time-matched CSF of 80 MOG-Ab-seronegative patients with demyelinating disease. METHODS: The cohort included 44 patients with NMOSD and related disorders and 36 patients with multiple sclerosis (MS). Two independent neurologists blinded to diagnosis analyzed MOG-Abs by live cell-based immunofluorescence assay with goat anti-human immunoglobulin (Ig) G (whole molecule) antibody. Sera were tested at dilutions of 1:20 and 1:40, and a cutoff of 1:160 was considered for serum positivity. CSF specimens were tested undiluted and at 1:2 dilution with further titrations in case of positivity. Anti-IgG-Fc and anti-IgM-µ secondary antibodies were used to confirm the exclusive presence of MOG-IgG in positive cases. CSF of 13 MOG-Abs seropositive cases and 36 patients with neurodegenerative conditions was analyzed as controls. RESULTS: Three seronegative cases had CSF MOG-Abs (4% of the whole cohort or 7% of cases excluding patients with MS, in which MOG-Abs seem to lack diagnostic relevance). In particular, 2 patients with neuromyelitis optica spectrum disorder (NMOSD) and 1 with acute disseminated encephalomyelitis had MOG-Abs in CSF. Analysis with anti-IgG-Fc and anti-IgM confirmed the exclusive presence of MOG-IgG in the CSF of these patients. Among the control group, MOG-Abs were detectable in the CSF of 8 of 13 MOG-Ab-seropositive cases and in none of the patients with neurodegenerative disorders. CONCLUSION: Although serum is the optimal specimen for MOG-Ab testing, analyzing CSF could improve diagnostic sensitivity in seronegative patients. This observation has relevant diagnostic impact and might provide novel insight into the biological mechanisms of MOG-Ab synthesis