Objectives: The etiology of epilepsy remains unknown in most cases. We sought to investigate the role of some pre-, peri- and postnatal factors in the etiology of idiopathic and cryptogenetic partial epilepsy. Methods: We carried out a community-based case-control study using the incidence cohort of epileptic patients living in the district of Copparo, in the province of Ferrara, Italy. The study was performed in 55 cases and 165 controls. A standardized questionnaire was used to collect information in face-to-face interviews. Results: Multivariate logistic regression analysis found that a personal history of febrile convulsions [odds ratio (OR) = 4.01, 95% confidence interval (CI) = 1.3–19.1] and a family history of seizures in first-degree relatives (OR = 4.5, 95% CI = 1.8–18.6) were independent risk factors for the condition under study. We failed to demonstrate an association between partial epilepsy and previously suggested perinatal risk factors. Conclusion: The findings of this study further support the hypothesis of a genetic propensity for seizures, which may be expressed early by the occurrence of febrile convulsions.

OBJECTIVES:To identify early predictors of intractability in childhood and adolescence epilepsy.MATERIALS AND METHODS:We carried out a community-based case-control study using the incidence cohort of epileptic patients living in the district of Copparo, in the province of Ferrara, Italy. The comparative study was performed in 31 cases and 95 controls. Cases were patients who averaged at least 1 unprovoked seizure per month during an observational period of at least 2 years. Controls were subjects having achieved remission for at least 5 years regardless of current therapy.RESULTS:Onset at age <1 year, remote symptomatic etiology and high frequency of seizures before therapy were found to be independent early predictors of intractability.CONCLUSION:Our study suggested that the risk of developing intractable epilepsy may, to some extent, be predicted at the time of initial diagnosis in children with early-onset epilepsy of remote symptomatic etiology, especially if seizure propensity is initially high.

A community-based cross-sectional study was carried out in Ferrara, Northern Italy, to verify the frequency of gingival overgrowth in chronic phenytoin (PHT) users and the risk factors associated with its development. All subjects taking phenytoin were identified using the computerized list of drug prescriptions available in the study area. Most of the subjects were interviewed and underwent an oral examination to evaluate their periodontal condition. The prevalence of gingival enlargement in chronic PHT users was about 40%. In our study, sex, age age at onset of therapy, treatment duration, and oral hygiene were not significantly associated with the risk of developing gingival overgrowth. A direct relationship with daily dose was found to be an independent risk factor. Younger age and poorer oral hygiene seemed to predispose to the severest level of gingival involvement. These results support data from experimental studies by suggesting that drug-induced gingival overgrowth is a dose-dependent side effect whose severity could be affected by local factors.

1 -neoplasms 248 -tumors 308 Bulgaria 304

A retrospective study was carried out in the Ferrara Local Health District, Italy, for the period 1981-1993 (average resident population: 177,235 inhabitants) to establish whether people exposed to exogenous gangliosides had a higher risk of Guillain-Barré syndrome. The incidence of Guillain-Barré syndrome of 1.9/100,000 population/year [95% confidence interval (CI): 1.3-2.5] reported in Ferrara Local Health District in the same period was used as a reference for comparison. The data bank of Ferrara Local Health District made it possible, first to estimate the number of individuals exposed to gangliosides in the resident population of Ferrara Local Health District (3.7%), the number of ganglioside prescriptions and the number of cases of Guillain-Barré syndrome who had treatment with gangliosides (nine patients, 20.9%), and, secondly, to verify the sequence of events between the ganglioside injection and the onset of the disease. Seven of the nine patients (77.8%) received gangliosides as treatment for peripheral neuropathy (Guillain-Barré syndrome onset before gangliosides were prescribed). For the other two patients (22.2%) a possible appropriate temporal sequence between ganglioside injection and onset of Guillain-Barré syndrome was found. Based on two possible ganglioside-related cases, the risk of Guillain-Barré syndrome was higher in the exposed (0.53/100,000 population/month following ganglioside injection; 95% CI: 0.06-1.91) compared with the unexposed population, but the difference was not significant. When only individuals prescribed with mixed gangliosides were considered (both possible ganglioside-related Guillain-Barré syndrome cases received mixed gangliosides), the risk of Guillain-Barré syndrome was higher (0.64/100,000 population/month following ganglioside injection; 95% CI: 0.08-2.31) but the difference from the risk in unexposed individuals was not statistically significant. The relative risk for the exposure to mixed gangliosides was borderline (relative risk = 4.3; 95% CI: 1.0-17.8). The wide 95% confidence intervals were a consequence of sample size limitations. Considering also that the exposed and unexposed groups differed in age (those exposed were older than those unexposed and the age-specific incidence of Guillain-Barré syndrome in the study population increased with increasing age), the present findings question either a strong increased risk of Guillain-Barré syndrome in people exposed to exogenous gangliosides or an immunogenic role of these agents in humans. However, because of the limited sample size, the results are not conclusive.

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.

A prospective study in patients with a clinical acute isolated brainstem or spinal cord disorder was undertaken. The aim was to evaluate the predictive value of IgG intrathecal synthesis (through the detection of oligoclonal bands in CSF) and MRI lesions at presentation, for the subsequent progression to multiple sclerosis. Forty four patients took part in this study: 22 had a brainstem disorder and 22 a spinal cord disorder. After a mean period of 26 (SD 22) months, 30 patients (68.2%) developed clinically definite multiple sclerosis. The remaining 14 patients were followed up for more than seven years. Twenty six (59.1%) patients had oligoclonal bands in CSF, with a sensitivity of 80.0%, specificity of 85.7%, and a predictive value of 92.2%. Magnetic resonance imaging showed disseminated white matter lesions in 22 patients (50.0%), with a sensitivity of 60.0%, a specificity of 71.4%, and a predictive value of 81.7%. The difference between patients with multiple sclerosis and patients without the disease was statistically significant for the findings of an IgG intrathecal synthesis (P < 0.001). It was only borderline for the MRI findings (P = 0.052). Thus the detection of an intrathecal synthesis at presentation seemed to be a better prognostic indicator of the progression to multiple sclerosis in patients affected by acute isolated brainstem or spinal cord syndromes.

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.

The Guillain-Bare syndrome (GBS) incidence has been updated in the area of the Local Health District of Ferrara, Unita Sanilaria Locale n. 31 (USL 31), Northern Italy, (where a previous survey found an average annual incidence of 1.26/100 000 population) in order to verify a supposed increase in GBS occurrence. The updated mean annual incidence over the years from 1981 to 1993 (average resident population: 177 235 inhabitants) was 1.87/100 000 population (1.66/100 000 when age-adjusted). The rate increased progressively in the four subsequent time intervals into which the study period was subdivided (from 1.09/100 000 in the years 1981-1984 to 2.73/100 000 in the years 1991-1993) with a significant temporal variation (0.025 < p < 0.05). The incidence was higher in the urban centres than in the rural zone of USL 31 (2.22/100 000 and 1.10/100 000; 0.025 < p < 0.05) and an increase of GBS risk in the urban area was found. The incidence showed an increase in the oldest age groups of the study population. These findings seem to confirm a slight increase of GBS risk in the area of Ferrara with particular reference to urban centres and elderly people.

It is generally agreed upon that the attacks of migraine with aura are indicative of abnormal cerebral perfusion, while the permanence of such perfusion abnormalities during the pain-free intervals of migraine remains debated. This study was aimed at assessing: 1) the presence of cerebral perfusion abnormalities also during the interictal phase and 2) the role of SPET with 99mTc HM-PAO to diagnose migraine. Twenty-eight patients (22 women and 6 men), diagnosed as having migraine with aura according to the International Headache Society (Headache Classification Committee criteria), were submitted to SPET studies, within 10 days of the last attack. 99mTc HM-PAO was used as perfusion tracer and a single head rotating gamma camera equipped with a high-resolution collimator was used for data acquisition. The qualitative analysis of SPET images showed slight hypoperfusion areas in 22 of 28 patients (79%). In 12 of 22 patients (55%) a regional correlation was observed between hypoperfusion areas and the neurologic symptoms of aura. The results of the present study are in agreement with the current physiopathologic interpretation of migraine with aura, confirming the instability of cerebral perfusion control, even with instrumental evidence of perfusion abnormalities in the interictal period. Moreover, SPET with 99mTc Hm-PAO seems to be a useful tool in the diagnostic assessment of migraine.

Summary: We examined the etiopathogenetic role of pre‐ perinatal 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 de‐ velops into epilepsy.

INTRODUCTION:The well-established relationship between myasthenia gravis (MG) and HLA antigens varies among different ethnic groups. In Caucasians B8 and/or DR3 alleles have been found associated with young MG women without thymoma and with high titres of acetylcholine-receptor antibody (AChR Ab). An increased frequency of haplotype HLA-A3, B7 and/or DR2 has been observed in older MG patients with low AChR Ab levels. So far, there is no convincing evidence for an association between a specific haplotype HLA and ocular MG or MG with thymoma. MG subjects often show other concurrent autoimmune disorders suggesting a more general inherited predisposition to autoimmunity. We performed a community-based study to verify the HLA-A, B, C, DR and DQ profile on ethnically homogeneous MG patients and with the aim to estimate the frequency of concurrent autoimmune diseases and to compare HLA phenotypes to autoimmune status in different MG patients groups.METHODS:Forty-seven patients, living in the province of Ferrara, were followed-up in our neurologic department and typed for HLA Antigens. In addition a set of immunological laboratory tests was performed.RESULTS:We found a trend towards an increased B8 and DR3 frequencies in total affected population; an association between B8 allele and early onset of generalized MG sustained by thymic hyperplasia. The DR3 allele is statistically associated with the presence of additional autoimmune disorders.CONCLUSIONS:Our data support the hypothesis of a genetically-based heterogeneity of the disease and show an increased prevalence of associate autoimmune conditions in MG patients.

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.

INTRODUCTION:The period prevalence rate for anti-parkinson drugs (APD) use was reported in the Local Health Service of Ferrara (USL 31), Northern Italy, in 1988 (resident population: 177,000 inhabitants).MATERIAL AND METHODS:The study was performed through the analysis of the complete list of APD prescriptions in the USL 31 area provided by the computerized archives of USL 31 and the identification code of the patients which is unique for each resident of USL 31. The patients treated with neuroleptics known to be potential parkinsonism-inducing drugs were excluded.RESULTS:The period prevalence rate for APD users was 456.9 per 100,000 population. The prevalence rate for dopa derivatives users was 391.3 per 100,000. The prevalence did not varied between rural and urban zones of USL 31 both for APD and dopa derivatives users. A higher prevalence was obtained in a small rural commune of USL 31 both for APD users (758.5 per 100,000) and dopa derivatives users (718.6 per 100,000) than in the other 4 communes in which the study area is subdivided.CONCLUSION:The reported prevalence could provide information on the occurrence of most parkinsonisms in the study area and some suggestion on the role of possible environmental factors.

INTRODUCTION:We planned a descriptive study on the incidence of intracranial gliomas spanning a 16-year period (1976-1991) in the Local Health Service 31 of Ferrara, Northern Italy.MATERIAL AND METHODS:We used a complete enumeration approach by reviewing all the possible sources of case collection available in the study area.RESULTS:The mean annual incidence rate was 5.8 new cases per 100,000 population (6.96 for men and 4.78 for women; p < 0.05), resulting in 4.7 per 100,000 when directly adjusted to the Italian population. The age-specific incidences showed a small peak in childhood, an increase with age, reaching a maximum in the age group 60 to 64 and then a decline in the elderly. This pattern is similar for both sexes. The adjusted rates increased from 3.94 per 100,000 population in the first five-year period to 5.6 per 100,000 in the third (a nonsignificant difference). The distribution of cases within the study area was substantially uniform.CONCLUSION:The incidence rates of Ferrara fell into the middle-high values so far reported and confirmed the male preponderance found in previous studies. The age-related pattern is similar to that observed, with few exceptions, in other surveys. Like other authors we did not find a significant temporal trend, although the incidence rates tended to increase with time. The data encourage further, wider epidemiological studies of a prospective nature.