Giuseppe Salemi

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.

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.

Gender-related effect of clinical and genetic variables on the cognitive impairment in multiple sclerosis

Abstract.Background:Cognitive impairment may occur at any time during the course of multiple sclerosis (MS), and it is often a major cause of disability in patients with the disease. The APOE-ε4 allele is the major known genetic risk factor for late onset familial and sporadic Alzheimer’s Disease (AD), and it seems to be implicated in cognitive decline in normal elderly persons.Objective:To investigate the clinical and genetic variables that can be associated with the cognitive decline in patients with MS.Methods:Five-hundred and three patients with clinically definite MS underwent a battery of neuropsychological tests and, according to the number of failed tests, were divided into cognitively normal and impaired. All patients were genotyped for APOE gene polymorphisms.Results:Fifty-six percent of MS patients showed, to different extents, cognitive impairment. Cognitive decline was predominant in men and was associated with disease duration, Kurtzke Expanded Disability Status Scale (EDSS) score, a low level of education, and, interestingly, the ε4 allele of the APOE gene. By contrast, cognitive impairment in women was independent of any investigated variable.Conclusion:The findings demonstrate that clinical and genetic factors play a role in men affected by MS developing cognitive impairment.

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.

Real-life impact of early interferonβ therapy in relapsing multiple sclerosis

Recent findings support greater efficacy of early vs. delayed interferon beta (IFNβ) treatment in patients with a first clinical event suggestive of multiple sclerosis (MS). We aimed to evaluate the effectiveness of early IFNβ treatment in definite relapsing‐remitting MS (RRMS) and to assess the optimal time to initiate IFNβ treatment with regard to the greatest benefits on disability progression.

Correlation between fatigue and brain atrophy and lesion load in multiple sclerosis patients independent of disability.

BACKGROUND Fatigue is a major problem in multiple sclerosis (MS), and its association with MRI features is debated. OBJECTIVE To study the correlation between fatigue and lesion load, white matter (WM), and grey matter (GM), in MS patients independent of disability. METHODS We studied 222 relapsing remitting MS patients with low disability (scores <or=2 at the Kurtzke Expanded Disability Status Scale). Lesion load, WM and GM were measured by fully automated, operator-independent, multi-parametric segmentation method. T1 and T2 lesion volume were also measured by a semi-automated method. Fatigue was assessed by the Fatigue Severity Scale (FSS), and patients divided in high-fatigue (FSS>or=5; n=197) and low-fatigue groups (FSS<or=4; n=25). RESULTS High-fatigue patients showed significantly higher abnormal white matter fraction (AWM-f), T1 and T2 lesion loads, and significant lower WM-f, and GM-f. Multivariate analysis showed that high FSS was significantly associated with lower WM-f, and GM-f. Females and highly educated patients were significantly less fatigued. CONCLUSION These results suggest that among MS patients with low disability those with high-fatigue show higher WM and GM atrophy and higher lesion load, and that female sex and higher levels of education may play a protective role towards fatigue. Furthermore, they suggest that in MS, independent of disability, WM and GM atrophy is a risk factor to have fatigue.

Prevalence of essential tremor A door‐to‐door survey in Terrasini, Sicily

As part of a door-to-door neuroepidemiologic survey, we investigated the frequency and distribution of essential tremor (ET) in a Sicilian municipality. During phase 1, we administered a screening instrument for tremor to 7,653 persons residing in Terrasini (Palermo province). During phase 2, neurologists evaluated those subjects who had screened positive. The diagnoses, based on specified clinical criteria, were reviewed to increase reliability across neurologists. We found 31 subjects affected by ET (17 men, 14 women); 11 patients (35.5%) reported a familial aggregation. The prevalence of ET as of November 1, 1987, was 405.1 per 100,000 for the total population, and 1,074.9 per 100,000 for those 40 years old or older. The prevalence increased with advancing age for both sexes and was slightly but consistently higher in men. Comparison with other studies suggests striking geographic variation, which may reflect genetic differences.

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.

Mortality in multiple sclerosis: a review

This work was undertaken to evaluate studies on mortality caused by multiple sclerosis (MS), to evaluate if useful inferences can be drawn from survival studies that can be applied to clinical practice. A literature search was carried out to find epidemiological studies on MS prognosis, survival, mortality and causes of death relevant to our aim. The World Health Organization (WHO) reports on worldwide cause‐specific mortality were also considered. Studies were evaluated according to the duration of the follow‐up study, the year of publication and the methodology used. We evaluated MS survival from a methodological point of view and considered if time trends could be drawn from study results. We conclude that mortality is only slightly higher in MS patients when compared with that in the general population. Mortality is higher particularly for older patients and those with longer disease duration.