Education protects against cognitive changes associated with multiple sclerosis.

PURPOSE: Although neuropsychological impairments are common in Multiple Sclerosis (MS), the manifestation of cognitive deficits may vary greatly across MS patients. Here, we explored the influence of cognitive reserve proxy indices (education and occupation) and perceived fatigue on cognitive performance. METHODS: Fifty relapsing-remitting MS patients were evaluated. Cognitive performance was measured using the Paced Auditory Serial Addition Test (PASAT), in which information processing speed can be manipulated by varying the presentation speed of stimuli. RESULTS: MS patients with low education performed worse than healthy controls at faster PASAT speeds. By contrast, no difference was observed between MS patients with high education and matched healthy controls, regardless of PASAT speed. Moreover, we found that neither occupational attainment nor perceived fatigue has an influence on MS patients' cognitive performance. CONCLUSION: These findings provide evidence that higher education could be protective against MS-associated cognitive deficits and that high speed PASAT versions are more suitable for identifying compensatory capacities compared to low speed PASAT versions.

Effect of the disclosure of MS diagnosis on anxiety, mood and quality of life of patients: a prospective study.

BACKGROUND: In the light of the new diagnostic criteria for multiple sclerosis (MS) and currently available early treatment, this study aimed to explore whether, and to what extent, disclosure of the diagnosis of MS or clinically isolated syndrome (CIS) affects patients' anxiety, mood and quality of life (QoL). METHODS: Eligible participants were all patients referred for the first time to the Neurological Unit who had manifested symptoms suggestive of MS for no more than 6 months. All patients were evaluated for (i) QoL (SEIQoL and MS-QoL54), (ii) Anxiety (STAI) and Depression (CMDI) on study inclusion (T0), 30 days after diagnosis disclosure (T30), and after 1 (T1y) and 2 (T2y) years' follow-up. RESULTS: Two hundred and twenty-nine patients were enrolled; 93 of these were unaware of their diagnosis. Patients who already knew their diagnosis (100 with CIS and 22 with MS) were excluded from the main analyses and used to perform control analyses. At the end of the screening, an MS diagnosis was disclosed to 18 of the 93 patients, whereas a CIS diagnosis was disclosed to 62 patients (12 patients received a diagnosis other than MS or CIS). Thirty days after diagnosis disclosure, irrespective of the diagnosis disclosed, both QoL and Anxiety and Depression were significantly rated as better compared to the start of screening, (p(s) < 0.03), and this improvement remained stable over the two annual follow-ups. However, as suggested by a significant 'Time' × 'Diagnosis' interaction with regard to both QoL and Anxiety and Depression (p(s) < 0.02), the effect of the disclosure in the short term differed depending on CIS or MS diagnosis. Specifically, on MSQoL, which is a health-related QoL scale, we found a statically significant improvement, immediately after the diagnosis disclosure, in both the MS and CIS groups (p(s) < 0.01). Differently, on SEIQoL, which is a non health-related QoL measure, and on the anxiety scale, we observed a statistically significant improvement only in the group which received a MS diagnosis (p(s) < 0.03). CONCLUSIONS: This first prospective study provides objective data showing that early disclosure of MS diagnosis improves both the patient's QoL and psychological well-being. In addition, the results seem to suggest that CIS disclosure does not lead to the same favourable effects.

Pergolide monotherapy in the treatment of early PD: a randomized, controlled study. Pergolide Monotherapy Study Group.

OBJECTIVE: To determine whether pergolide monotherapy provides symptomatic relief in early PD. BACKGROUND: Early treatment with dopamine agonists may reduce the risk of motor fluctuations, which are most likely linked to levodopa therapy. Pergolide, a D1-D2 dopamine agonist, has been studied as "add on" therapy in PD, but no controlled clinical trial studying the efficacy of pergolide monotherapy is available. METHODS: The efficacy and tolerability of pergolide were evaluated in a multicenter, double-blind, randomized, parallel-group, 3-month trial versus placebo. Patients with a diagnosis of idiopathic PD, a modified Hoehn & Yahr score of 1 to 3, and a score greater than 14 points on the Unified Parkinson's Disease Rating Scale (UPDRS) part III at baseline were enrolled in the study (pergolide, n = 53; placebo, n = 52). RESULTS: Patient characteristics at study entry were comparable in the two study groups. The pergolide group showed a significantly greater percent of responders (defined as a -30% decrease in UPDRS part III score at end point) compared with placebo (57% versus 17%; p < 0.001). Pergolide-treated patients experienced a significantly greater improvement than placebo-treated patients (p < 0.001) in UPDRS (overall, part II, and part III) score, Schwab & England score, and Clinical Global Impression improvement score. By the study end the mean dose of pergolide was 2.06 mg/day. Six patients in the pergolide group versus two patients in the placebo group discontinued the study because of treatment emergent side effects. CONCLUSION: This study suggests that pergolide monotherapy may be an efficacious and well-tolerated first-line treatment in patients with early-stage PD.

Prognosis of childhood epilepsy: a community-based study in Copparo, Italy.

We performed a community-based study among children and adolescents with idiopathic and cryptogenic epilepsy and onset of the seizures between 0 and 19 years of age on the prognosis of being seizure-free. The study population was recruited during a descriptive investigation in the Local Health Service of Copparo (USL 34), Ferrara, Northern Italy. We included 111 patients (61 males and 50 females). The average length of follow-up was 18.8 years (ranging from 7 to 24 years). The cumulative probability of being in remission was 81.2% at 15 years after onset and the estimated percentage of patients in remission without therapy was 56% for the same time period. At 15 years after the onset of epilepsy, approximately 20% of patients continued to have seizures; nearly 25% continued to take antiepileptic drugs but had been free of seizures for at least 5 years; nearly 56% had been without seizures and free of medication for at least 5 years. Seizure type, gender, age at onset of the illness, epileptic abnormalities on EEG, family history of convulsive disorders, number and frequency of seizures prior to the start of treatment were found not to be helpful as prognostic factors. This community study, carried out on patients without the well known factors that adversely affect prognosis, confirms that the prospect of seizure control and for withdrawal of therapy is (generally) good.

Multiple sclerosis in Italy. A reappraisal of incidence and prevalence in Ferrara.

BACKGROUND: Previous descriptive surveys on multiple sclerosis (MS) in the province of Ferrara, northern Italy, carried out by our own epidemiological research group, pointed out that this area was not at low-medium risk for MS. OBJECTIVE: To verify the morbidity estimates and update the temporal trend of MS. DESIGN AND METHODS: We used a complete enumeration approach by reviewing all the possible sources of case collection available in Ferrara for 1965 through 1993. We included all patients with definite and probable MS according to the criteria of Poser et al. RESULTS: The mean annual incidence rate was 2.3 per 100,000 population (95% confidence interval, 2.0-2.6 per 100,000), 3.0 per 100,000 for women and 1.5 per 100,000 for men. On December 31, 1993, 249 patients (170 women and 79 men) suffering from definite or probable MS were living in the province of Ferrara, giving a crude prevalence rate per 100,000 population of 69.4 (95% confidence interval, 61.2-78.7), 90.8 for women and 46.0 for men. CONCLUSION: The data confirm that in Ferrara, MS occurs more frequently than previously suggested by the latitude-related epidemiological model, supporting the view that northern Italy is a high-risk area for the disease. While the prevalence rate is much higher than in our previous studies, probably owing to the increasing survival of the patients because of improving supportive care, the incidence rates, similar in magnitude to those observed in high-risk areas of northern and central Europe, have remained relatively stable over time.

Expansion of a (CAG)n repeat region in a sporadic case of HD.

The genetic mutation underlying Huntington's disease (HD) has been identified as an expansion and instability of a specific CAG repeat sequence in a gene on chromosome 4. A simple polymerase chain reaction assay has been used for the assessment of the (CAG)n expansion in a 72-year-old woman with typical HD symptoms, but no family history of the disorder. The DNA analysis showed that the patient had an allele with 41 repeat units, in the size range seen in HD chromosomes. Therefore, HD diagnosis is confirmed in this seemingly sporadic case and the disease is newly diagnosed in a large family. The risk of inheriting this unstable expanded allele is discussed. INTRODUCTION--The discovery of an expansion of a trinucleotide (CAG) repeat region in the IT15 gene on the short arm of chromosome 4 has identified the mutational mechanism causing Huntington's disease (HD) and enables the direct diagnosis of affected subjects based on DNA analysis alone. Here a 72-year-old woman with typical HD symptoms, but no family history of the disorder, has been unambiguously diagnosed by using a quick DNA analysis. This is relevant because the disease is newly diagnosed in a large family. MATERIAL AND METHODS--A labelled polymerase chain reaction (PCR) test has been used to amplify the repeat region of the IT15 gene and DNA fragments were analyzed by Polyacrylamide gel electrophoresis. RESULTS--The number the CAG repeats in the proband displayed two alleles of 23 and 41 repeats, respectively. Since normal chromosomes are reported to contain 11-34 repeats, the clinical appearance of HD in the proband is explained by the presence of the repeat expansion. DISCUSSION--The parents of the proposita both died aged over 80 y apparently without neurological signs referable to HD. Hence, this is presumably a sporadic case of the disease. Because of the length of 41 repeats of this HD chromosome, offspring of this proband could inherit the expanded allele with 37 repeats, as expected for the reversal of the trinucleotide expansion. A subject with this intermediate allele could be affected, but would not be affected if the HD IT gene with reduced triplets had recovered its normal function. Thus, in a seemingly sporadic case like the one reported here, despite the PCR analysis, the risk of transmission of HD to her offspring may remain uncertain.

Risk factors for idiopathic generalized seizures: a population-based case control study in Copparo, Italy.

We examined the etiopathogenetic role of preperinatal risk factors in the history of epileptic patients, identified in a previous descriptive study performed in Copparo, Italy. A community-based case control study of a group of epileptic patients with idiopathic generalized seizures was performed. The population consisted of 55 patients aged < 35 years as of December 31, 1988, residing in Copparo. Symptomatic patients were not included in the present study. The control sample consisted of 165 randomly selected healthy individuals, matched with patients for sex, age, and residence in the study area. The interview for detection of history of presumed risk factors was based on the Protocol of the Italian League Against Epilepsy. Obstetric, neurologic, and neonatal hospital charts were also reviewed. A family history of epilepsy, febrile seizures, and other perinatal factors (such as continual physical stress during pregnancy, maternal age > 35 years, and birth order > 3) were significantly more common in patients as compared with controls. Our data support the hypothesis of genetic propensity for generalized and febrile seizures, which may represent early expression of a low seizure threshold that subsequently develops into epilepsy.

Dietary habits and multiple sclerosis. A retrospective study in Ferrara, Italy.

In a retrospective case-control study of multiple sclerosis (MS), set up with the aim of verifying the role of environmental factors in pathogenesis, we included a section on dietary habits. We compared the frequency and pattern of food consumption by cases and controls. We found an association between. MS and high consumption of bread and "pasta", butter and lard, legume soup, horse flesh, coffee and tea in the period from infancy to adolescence. A different pattern of consumption of eggs, wine and mineral water between cases and controls was found during adulthood. Our results support, at least partially, the data already reported in the international literature on an association between certain dietary factors and MS. Some foods consumed at certain "critical" ages could play a causal role in the onset of MS.

Environmental risk factors and multiple sclerosis: a community-based, case-control study in the province of Ferrara, Italy.

The frequency of multiple sclerosis (MS) in Italy and in other areas of the world seems to have increased over time, suggesting that some environmental factors operate in its etiology. We performed a retrospective, community-based case-control study on MS in order to verify the etiologic role of selected environmental factors. We found an association between MS and higher educational level, employment in public administration, past history of allergies, and infection at an early age with measles, rubella and whooping cough. Our data seem to confirm that exogenous factors play a role in the etiology of MS although some confounding variables could have accounted for the associations.

Mortality study on multiple sclerosis in the province of Ferrara, northern Italy, 1968 through 1989.

A mortality study on Multiple Sclerosis (MS) was carried out in the province of Ferrara, Northern Italy, over the years from 1968 to 1989 (mean population 382,379 inhabitants) to outline the temporal trend of the disease in the residing population that can be regarded as a representative sample of the caucasians of Northern Italy. Given the difficulties in performing retrospective incidence studies over long time periods, the mortality rate was used as an indirect indicator of MS occurrence. Through a review of mortality tabulations with 340-345 ICD code and an intensive survey of all the MS cases, with successive check of the deceased ones at the general register offices of the study area communes, 56 MS patients who had lived and died in the province of Ferrara in the period 1968-1989 were selected with an average crude death rate of 0.67 per 100,000 per year (95% confidence interval: 0.51-0.87), 0.55 per 100,000 if adjusted to the Italian population. The death rate was stable over the considered time period with only a slight but insignificant increase in the last years of the survey. No differences were found among the rates from the 5 Local Health Units (USLs) in which the study territory is subdivided. The highest age-specific death rates were in the fifth and sixth decade of life and the average duration was 21.17 +/- 11.05 years. The results are consistent with a relatively stable MS risk in the population of the province of Ferrara and a homogeneous occurrence of the disease in the study territory.

Multiple sclerosis: does epidemiology contribute to providing etiological clues?

The epidemiological approach has undoubtedly contributed to our knowledge of Multiple Sclerosis (MS) by providing some etiological hypotheses in spite of the fact that a definitive basis for the conclusive resolution of its enigma is still lacking. Epidemiological studies have indicated that MS has an uneven geographical distribution and a changing incidence over time at least in several areas of the world: this suggests an etiological role of both genetic and environmental factors. The racial difference in disease risk, the results of familial and twin studies as well as the association between MS and some HLA markers, support the great importance of genetic factors. On the other hand, the evidence of temporal trends and the data from migrant studies seem to underline the etiological contribution of environmental factors. In the light of these results much of the present views have emerged interpreting the disease as caused by multiple factors acting at a susceptible age in genetically predisposed subjects.

[Huntington chorea in the province of Ferrara from 1971 to 1987. Descriptive study]. / La corea di Huntington nella provincia di Ferrara negli anni 1971-1987. Studio descrittivo.

In the context of a multidisciplinary study program whose purpose is to investigate the genetic aspects of Huntington's Chorea (HC), the authors conducted an epidemiological descriptive research extended to the population residing in the province of Ferrara in a time period including the years from 1971 to 1987. On December 31st, 1987 we estimated a prevalence rate of 1.89 cases of HC per 100,000 inhabitants; in the years 1971-1987 the incidence rate was of 0.11 per 100,000/year and the mortality rate of 0.06 per 100,000/year. In the last years considered for the study, the incidence and the prevalence showed a relative increase indicating that HC still exists in the ferrarese population, despite a greater public awareness. With the aim to organize preventive actions and to reach the preclinical diagnosis of the disease we singled out 83 subjects at risk the study area.