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.

Parkinson's disease in Ferrara, Italy, 1967 through 1987.

Epidemiological surveys on Parkinson's disease that have been carried out in different parts of the world have suggested that the disease is uniformly distributed in white populations. The position with regard to the Mediterranean peoples is still controversial, because of the large variation of the frequencies observed in the different areas that have been investigated. We therefore studied the frequency of Parkinson's disease in the Local Health Service of Ferrara, northeastern Italy (mean population, 187,000). Based on 394 patients, the mean incidence per year for the period from 1967 through 1987 was 10.01/100,000. The incidence rate of Parkinson's disease among cases with early onset was found to be statistically higher in rural areas as compared with urban ones (6.32/100,000 vs 3.11/100,000). Moreover, the study revealed a significantly higher incidence rate among agricultural workers (20.6/100,000). These results would seem to give further support to the hypothesis of a possible causal role of environmental factors that are mainly linked to agriculture, most likely due to the continual exposure to toxic agents in this area. However, further studies, which are not exclusively epidemiological, are necessary before any conclusions may be drawn, because many confounding variables may account for the results from surveys of this type.

Acute cerebrovascular insults in homozygous beta-thalassaemia: a case report.

Neurological complications following vascular thrombotic crises are frequent and occur in sickle cell anaemia and its variants, but are less well recognized in thalassaemias. A case of beta-thalassaemia major is reported complicated by an ischaemic lesion involving the right cerebellar hemisphere. The probable pathogenesis is considered and the literature on the matter briefly reviewed. In agreement with other reports, the interference of risk factors provided by or occurring in association with multiple blood-transfusions is hypothesized. Consequently, caution is recommended in giving large blood-transfusions to thalassaemic patients.

The incidence of Guillain-Barre syndrome in Ferrara, Italy: is the disease really increasing?

The Guillain-Barre syndrome (GBS) incidence has been updated in the area of the Local Health District of Ferrara, Unita Sanitaria Locale n. 31 (USL 31), Northern Italy, (where a previous survey found an average annual incidence of 1.26/10000 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: 177235 inhabitants) was 1.87/100000 population (1.66/100000 when age-adjusted). The rate increased progressively in the four subsequent time intervals into which the study period was subdivided (from 1.09/100000 in the years 1981-1984 to 2.73/100000 in the years 1991-1993) with a significant temporal variation (0.025

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.

Pure "aphasic" agraphia due to damage of the left superior parietal lobule.

A case of pure agraphia, due to an ischaemic lesion of the left superior parietal lobule, is reported. The neuropsychological analysis of writing performances suggests an aphasic nature of this patient's pure agraphia. The authors discuss the role played by diffuse and/or localized brain lesions in writing function, emphasizing that the left superior parietal lobule in man may be crucial for the sensorimotor linguistic integration needed for writing.

The frequency of multiple sclerosis in Italy: a descriptive study in Ferrara.

Results of intensive prevalence surveys on multiple sclerosis carried out in different small regions of Italy have suggested that this country falls into the high-frequency zone for the disease. To verify this hypothesis by studying a large population, we conducted intensive incidence and prevalence survey in the province of Ferrara, northern Italy (mean population, 386,000). Based on 128 patients, the mean incidence per year for the period 1965 through 1979 was 2.2 cases per 100,000. On October 24, 1981, the prevalence rate was 46.1 cases per 100,000. The results support the view that northern Italy is a high-risk area for multiple sclerosis.

[Significance and usefulness of SPECT with Tc-99m HMPAO in the diagnosis of hemicrania with aura]. / Significato ed utilità della SPET con 99mTc HM-PAO nella diagnostica dell'emicrania con aura.

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.

Prevalence of anti-parkinson drugs' use in Ferrara, northern Italy, 1988.

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.

A neurophysiological study on the P300 component of event-related potentials in Hakim-Adams syndrome.

We have explored the variability of P300 event-related potentials in patients affected by Hakim-Adams syndrome, with raised or intermittent intracranial pressure, treated with surgical cerebrospinal fluid shunting. The clinical utility of P300 is confirmed in the light of the improvement of neurophysiological data after the surgical procedure, parallel with amelioration of neuropsychological performances.

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.

Exogenous gangliosides and Guillain-Barré syndrome. An observational study in the local health district of Ferrara, Italy.

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.

A descriptive study of epilepsy in the district of Copparo, Italy, 1964-1978.

Worldwide investigation of the epidemiology of epilepsy has suggested wide variations in the frequency of convulsive disorders. However, descriptive studies in general populations cannot be completely comparable because of a remarkable methodological dishomogeneity in definition of epilepsy, classification of seizures, and ascertainment, collection, and selection of the cases. The position with regard to the Mediterranean people was still little known, and the few studies presently available from Italy offer underestimates of epilepsy frequency owing to incompleteness in case-collection practices and lack of information about the incidence of the disease. Therefore, to verify the true frequency of epilepsy in our country, we performed a community-based epidemiologic study of convulsive disorders in the district of Copparo (population 45,153) in northern Italy. Based on 278 accepted cases with "active" epilepsy, the prevalence per 1,000 population on December 31, 1978, was 6.2 (6.4 if standardized to the Italian population). The average annual incidence for the period 1964 through 1978 was 33.1 per 100,000 (38.3 if standardized). These results, similar to those found in other Western countries, support the view that the frequency of epilepsy in Italy as a whole is higher than that indicated by the Italian studies previously published, and suggest that epilepsy is evenly distributed in Europe and the United States. Antecedents which could be considered potential causes of epilepsy were found in 39.6%, and in 39.1% of the prevalence and incidence cases, respectively; for both prevalence and incidence groups, perinatal brain injuries were the most frequent event. This high proportion of epileptic cases with underlying causes emphasizes the urgency of planning precautionary measures in Italy to improve prenatal and perinatal medical care.

Early predictors of intractability in childhood epilepsy: a community-based case-control study in Copparo, Italy.

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.

[The combined use of instrumental and laboratory examinations in multiple sclerosis: is the diagnostic facilitation real?]. / Uso combinato degli esami strumentali e di laboratorio nella sclerosi multipla: è reale la facilitazione diagnostica?

Spatial-temporal dissemination of neurological signs is an essential criterion for establishing a definite diagnosis of Multiple Sclerosis (MS). Unfortunately, we often observe patients who present a history consistent with MS but without objectivity indicating the presence of at least two or more distinct lesions of Central Nervous System (CNS). In recent years, many Authors have emphasized the use of Multimodal Evoked Responses (MER), Cerebrospinal Fluid (CSF) analysis for the research of Oligoclonal Bands (OB), and Magnetic Resonance Imaging (MRI) as highly sensitive techniques for demonstrating the spreading of the lesions. This study, carried out to evaluate whether the combined use of these three methods would increase the diagnostic MS sensitivity, comprises 62 patients classified in Definite (n = 24). Probable (n = 18) and Possible (n = 20) MS according to the clinical criteria of McAlpine. All our cases fulfilled a complete ER evaluation (VER, SER, BAER), a paired CSF and serum Isoelectric focusing (IEF) and a cerebral MRI. Moreover, IgG Index was also estimated. CSF IEF was the most sensitive test in Definite (91.7%) and Possible (80.0%) MS, nearly followed by MRI (87.5% and 45.0% respectively). VER (87.5% and 60.0%) and SER (87.5% and 65.0%). On the contrary, MRI showed the higher sensitivity in Probable MS (94.4%). The course of the disease influenced only SER and VER in all diagnostic group, while the duration correlated positively with BAER and VER. Only VER and BAER, finally, supplied additional information about the not revealed clinically or by MRI CNS disorders. Thus, our data further emphasize the value of combining these laboratory tests for establishing an early and more accurate diagnosis of MS.

Epidemiology of Parkinson's disease in Italy. A descriptive survey in the U.S.L. of Cento, province of Ferrara, Emilia-Romagna.

In order to verify the epidemiology of Parkinson's disease in northern-Italy, we carried out a descriptive study in the Local Health Service No. 30 of Cento, Emilia-Romagna. Based on 73 accepted cases, the prevalence rate on December 31, 1987, was 190.3 per 100,000 population. No significant difference was reported between the two sexes. The highest rates were observed in the age groups over 60 years. Our data indicate that the risk of Parkinson's disease in northern-Italy is similar to that observed in other Caucasian populations.

Phenytoin-induced gingival overgrowth: a community-based cross-sectional study in Ferrara, Italy.

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.

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.

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.