Giovanni Savettieri

Multiple Sclerosis Severity Score Using disability and disease duration to rate disease severity

Background: There is no consensus method for determining progression of disability in patients with multiple sclerosis (MS) when each patient has had only a single assessment in the course of the disease. Methods: Using data from two large longitudinal databases, the authors tested whether cross-sectional disability assessments are representative of disease severity as a whole. An algorithm, the Multiple Sclerosis Severity Score (MSSS), which relates scores on the Expanded Disability Status Scale (EDSS) to the distribution of disability in patients with comparable disease durations, was devised and then applied to a collection of 9,892 patients from 11 countries to create the Global MSSS. In order to compare different methods of detecting such effects the authors simulated the effects of a genetic factor on disability. Results: Cross-sectional EDSS measurements made after the first year were representative of overall disease severity. The MSSS was more powerful than the other methods the authors tested for detecting different rates of disease progression. Conclusion: The Multiple Sclerosis Severity Score (MSSS) is a powerful method for comparing disease progression using single assessment data. The Global MSSS can be used as a reference table for future disability comparisons. While useful for comparing groups of patients, disease fluctuation precludes its use as a predictor of future disability in an individual.

Prevalence of Parkinson's disease and other types of parkinsonism A door‐to‐door survey in three Sicilian municipalities

We investigated the prevalence of Parkinsons disease and other types of parkinsonism in a Sicilian population using a door-to-door two-phase approach. This design called for the administration of a brief screening instrument to all subjects who, on November 1, 1987, were residents of Terrasini (Palermo Province), Santa Teresa di Riva (Messina Province), and Riposto (Catania Province), Sicily (N = 24,496). Study neurologists using specified diagnostic criteria extensively investigated those subjects who screened positive. We found 63 subjects affected by Parkinsons disease, 21 with secondary parkinsonism, and seven with unspecified parkinsonism. The crude prevalence per 100,000 population was 371.5 for all types of parkinsonism and 257.2 for Parkinsons disease; for both entities, prevalence increased steeply with age and showed an inconsistent sex pattern. Our prevalence figures for Parkinsons disease are higher than those previously reported in Italy or elsewhere, which may be due, in part, to more complete case-ascertainment.

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.

Risk of Parkinson disease in women Effect of reproductive characteristics

Objective: To investigate the association between some fertile life characteristics and Parkinson disease (PD) in women. Methods: Women affected by PD and control subjects were matched one to one by age (±2 years). One hundred thirty-one women with idiopathic PD and 131 matched control subjects were interviewed. Controls were randomly selected from the resident list of the same municipality of residence of cases. All subjects had a Mini-Mental State Examination score of ≥24. Cumulative length of pregnancies, age at menarche, age and type of menopause, and estrogen use before and after menopause were investigated in cases and controls through a structured questionnaire. Models of matched pair univariate analysis and conditional logistic regression analyses were used to calculate adjusted odds ratio (OR), 95% CI, and two-tailed p values for the investigated variables. Results: PD was significantly associated with a fertile life length shorter than 36 years (OR 2.07; 95% CI 1.00 to 4.30) and a cumulative length of pregnancies longer than 30 months (OR 2.19; 95% CI 1.22 to 3.91). An inverse association between PD and surgical menopause (adjusted OR 0.30; 95% CI 0.13 to 0.77) was also found. Conclusions: An association between factors reducing estrogen stimulation during life and PD was found. These results support the hypothesis that endogenous estrogens play a role in the development of PD.

Prevalence of cervical spondylotic radiculopathy: a door‐to‐door survey in a Sicilian municipality

Introduction— Because of the limited information on cervical spondylotic radiculopathy, we conducted a door‐to‐door two‐phase survey in a Sicilian municipality. Material and methods ‐ We first screened for cervical spondylotic radiculopathy among the inhabitants of the municipality: (N= 7653, as of the prevalence day, November 1, 1987). Study neurologists then investigated those subjects suspected to have had a cervical spondylotic radiculopathy. Diagnoses were based on specified criteria. Results— We found 27 subjects affected by CSR (17 definite, 10 possible). Prevalence (cases per 1000 population) was 3.5 in the total population; it increased to a peak at age 50–59 years and decreased thereafter. The age‐specific prevalence was consistently higher in women. Conclusions— Comparison with other prevalence studies shows similar age‐specific patterns, but different magnitudes, which may partly reflect methodologic differences across studies.

High incidence and increasing prevalence of MS in Enna (Sicily), southern Italy

Twenty years after a first survey, a follow-up study was performed on the prevalence of MS in Enna (Sicily), southern Italy. The prevalence of definite MS rose from 53 to 120.2 per 100,000 population. The incidence of definite MS for the period 1986 to 1995 was 5.7 per 100,000 per year. The innermost part of Sicily shows an elevated prevalence of MS, second only to Sardinia in the Mediterranean area.

The HLA locus and multiple sclerosis in Sicily.

The authors report the analysis of HLA-class II allelic heterogeneity in a well characterized multiple sclerosis (MS) Sicilian dataset. Family-based association analysis revealed evidence for excess transmission to affected individuals for alleles HLA-DRB1*1501, DRB1*04, and DQB1*0302. When analyzed as haplotypes, the authors observed excess transmission for the DRB1*0400-DQB1*0302 haplotype. Sicilian patients share the HLA-DRB1*1501 susceptibility allele with affecteds living in continental Italy, but also display the allelic heterogeneity that characterizes Mediterranean populations.

Prevalence and incidence of multiple sclerosis in the city of Monreale, Italy

Abstract The prevalence and incidence of multiple sclerosis (MS) in the city of Monreale, southern Italy were ascertained 10 years after a preliminary study in the same area. The study was undertaken in a population of 26,256 people. The patients were classified according to Poser’s criteria. The prevalence of MS on 31 December 1991 was 72.4 per 100,000 population. The incidence of MS for the period 1981–1991 was 3.3/100,000 per year. The mean period between onset and diagnosis of MS was 4.9 years for those patients found during this survey and 9.2 years for those in the first study. This study shows an increase of MS prevalence in Monreale city and a high incidence. The findings parallel the reduction of the lag time between onset and diagnosis.

Incidence of amyotrophic lateral sclerosis in Sicily: A population based study.

Abstract Our objective was to investigate incidence of amyotrophic lateral sclerosis (ALS) in Sicily, southern Italy, by means of a population based study. We included people with ALS resident in five Sicilian provinces, whose onset occurred in the two-year period 2005−2006 (population at 31 December 2006: 3,481,096 inhabitants). A multisource case-finding procedure was adopted and patients were classified as affected by ALS according to revised El Escorial criteria. During the two-year surveillance period, 97 patients meeting eligibility criteria included 57 males (58.8%) and 40 females (41.2%). Crude annual incidence rate was 1.4/100,000 person years (95% CI 1.33−1.47). The incidence rate was higher in males (1.71/100,000; CI 1.61−1.81) than in females (1.11/100,000; CI 1.01−1.21). Standardized incidence rate for the total population in the 45−74-years-old age group was 3.22 (CI 3.11−3.33). Prevalence rate was 6.0/100,000 (CI 5.97−6.03), higher in males (7.1/100,000; CI 7.02−7.18) than females (4.9/100,000; CI 4.86−4.94). In conclusion, ALS rates observed in the present study are higher in males than females, with a peak of incidence at 70 years of age in both genders. These findings are consistent with those of other population based European studies.

Lack of association between ubiquitin carboxy-terminal hydrolase l1 gene polymorphism and PD

In 1998, an IL93Met mutation in the ubiquitin carboxy-terminal hydrolase L1 ( UCH-L1 ) gene was identified in a German family affected by PD.1 Recently, others2-4⇓⇓ found that the S18Y polymorphism in exon 3 of UCH-L1 is associated with a low risk of PD. To verify these interesting results, we decided to design a case-control study on the S18Y polymorphism of the UCH-L1 gene using sporadic PD cases. In the meantime, as we were analyzing our samples, a case-control study5 on 142 patients with PD and 142 age- and sex-matched control subjects did not confirm the protective effect found by Maraganore et al.2 In view of these conflicting findings, we reasoned that our contribution may have some weight in defining the role of the UCH-L1 gene in PD.nnBlood was collected from 169 patients with sporadic PD and 165 control subjects. Patients and control subjects were not matched for age and sex. Patients with PD were consecutively selected starting from January 1999 until September 2000 from among …