Amyotrophic Lateral Sclerosis and Air Pollutants in the Province of Ferrara, Northern Italy: An Ecological Study.

The etiopathogenesis of amyotrophic lateral sclerosis (ALS) is still largely unknown, but likely depends on gene-environment interactions. Among the putative sources of environmental exposure are air pollutants and especially heavy metals. We aimed to investigate the relationship between ALS density and the concentration of air pollution heavy metals in Ferrara, northern Italy. An ecological study was designed to correlate the map of ALS distribution and that of air pollutants. All ALS cases diagnosed between 2000 and 2017 (Ferrara University Hospital administrative data) were plotted by residency in 100 sub-areas, and grouped in 4 sectors: urban, rural, northwestern and along the motorway. The concentrations of silver, aluminium, cadmium, chrome, copper, iron, manganese, lead, and selenium in moss and lichens were measured and monitored in 2006 and 2011. Based on 62 ALS patients, a strong and direct correlation of ALS density was observed only with copper concentrations in all sectors and in both sexes (Pearson coefficient (ρ) = 0.758; p = 0.000002). The correlation was higher in the urban sector (ρ = 0.767; p = 0.000128), in women for the overall population (ρ = 0.782, p = 0.000028) and in the urban (ρ = 0.872, p = 0.000047) population, and for the older cohort of diagnosed patients (2000-2009) the assessment correlated with the first assessment of air pollutants in 2006 (ρ = 0.724, p = 0.008). Our data is, in part, consistent with a hypothesis linking copper pollution to ALS.

The Incidence of Myasthenia Gravis in the Province of Ferrara, Italy, in the Period of 2008-2022: An Update on a 40-Year Observation and the Influence of the COVID-19 Pandemic.

Myasthenia gravis (MG) is the most common neuromuscular junction disorder. We evaluated the MG incidence rate in the province of Ferrara, Northern Italy, over two time frames (2008-2018 and 2019-2022, i.e., the COVID-19 pandemic) and considered early-onset (EOMG), late-onset (LOMG), and thymoma- and non-thymoma-associated MG. Moreover, in the second period, we assessed its possible relationship with SARS-CoV-2 infection or COVID-19 vaccination. We used a complete enumeration approach to estimate the MG incidence and its temporal trend. For the period of 2008-18, 106 new cases were identified (mean incidence rate 2.7/100,000 people). The highest rates were observed for the over-70 age group and in rural areas, with 17% of thymoma-associated MG. During the COVID-19 period, 29 new cases were identified (average incidence rate 2.1/100,000 people), showing a marked (though not statistically significant) decrease in the mean annual incidence compared to the previous period. Again, the highest rate was observed for the over-70 age group. The first period was in line with our previous observations for the period between 1985 and 2007, highlighting a rising incidence of LOMG and a marked decrease in EOMG. During the COVID-19 period, incidence rates were lower in the first years whereas, when the pandemic ended, the previous trend was confirmed.

Development of Parkinsonism in a Patient with Central Pontine Myelinolysis.

Osmotic demyelination syndrome (ODS) is caused by damage to the pons myelin sheath and nerve cells. Although the pathophysiological mechanism responsible for the damage is not yet fully understood, it is currently believed that osmotic-type changes (especially if they are massive and too rapid) cause oedema that leads to compression and, subsequently, demyelination of white matter fibres. It generally manifests with acute paraparesis/tetraparesis, dysphagia, dysarthria, diplopia, and loss of consciousness, as well as hallucinations, spasms, and other neurological symptoms related to brainstem damage. In extreme cases, the locked-in syndrome may also appear. Of note, in some cases an association between osmotic demyelinating damage and the onset of movement disorders has been documented and, although the pathophysiology is still unknown, a correlation has been postulated between ODS and movement disorders. Here, we present a patient with ODS who developed parkinsonism, thus supporting the hypothesis of a correlation between these pathological events.

The distribution of the transient global amnesia in the province of Ferrara, Italy, a clue to the pathogenesis?

The pathophysiology of transient global amnesia (TGA) is still uncertain. In the province of Ferrara (Fe-province), Italy, given the health organization and the alarming clinical features, the cases of TGA in the resident population virtually correspond to the resident outpatients diagnosed as TGA cases in the ER of the University Hospital of Ferrara. Thanks to this, a retrospective survey identified 35 (14 men, 21 women) first-ever TGA cases in the resident population in 2018 (346,975 inhabitants) giving a crude incidence rate of 10.10/100,000 (95% CI 7.00-14.00), 8.40/100,000 (95% CI 4.60-14.10) for men, and 11.60/100,000 (95% CI 7.20-17.80) for women, a non-significant gender difference. The incident cases of TGA were evenly distributed according to both season and month. The monthly cases of TGA followed the Poisson distribution (goodness-of-fit test: λ = 2.9, χ2 = 2.557, 5 degrees of freedom, p > 0.70). The incidence of TGA in the Fe-province was higher in the highest level of urbanization (21.40/100,000 95% CI 13.10-33.00) than in the lowest one (4.20/100,000 95% CI 1.92-8.00). The incident cases of TGA increased with the level of urbanization (χ2 trend test = 19.940, p < 0.001) and the population density (inhabitants/km2) level (χ2 trend test = 46.684, p < 0.001). Since urbanization is likely involved in stress-related disorders, these findings achieved in a well-defined homogeneous population seem to support the hypothesis of the involvement of stress, maybe in vulnerable individuals, in TGA.

Incidence study of Guillain-Barré syndrome in the province of Ferrara, Northern Italy, between 2003 and 2017. A 40-year follow-up.

BACKGROUND: Guillain-Barré syndrome (GBS) is an acute/subacute autoimmune inflammatory polyradiculoneuropathy. Previous epidemiological studies carried out in the province of Ferrara, Italy, from 1981 to 2002 indicated that GBS incidence had tendency of increase in the period considered. OBJECTIVES: We aimed at updating the epidemiology of GBS in the years 2003-2017 and carrying on the work started in the 1980s. METHODS: We conducted an incidence study, by adopting a complete enumeration approach. Cases were identified from administrative, medical records, and database of the Ferrara Hospital and other provincial structures of the study area. Case ascertainment and definition are analogous to those adopted in previous surveys. RESULTS: In the period 1 January 2003 to 31 December 2017, 73 patients living in the province of Ferrara (mean population 353,142) were found to be new cases of GBS fulfilling the NINCDS criteria. Male/female ratio 1.15. The mean incidence rate was 1.38 per 100,000 (95% CI 1.08-1.74), 1.54 per 100,000 for men and 1.23 per 100,000 for women, a nonsignificant difference. During the period considered, the rates had slow increase or mild decrease, without nonsignificant difference. The highest rates were observed for the age groups 70-79 years for both sexes. A half of patients reported infectious events in the weeks before the onset of symptoms. CONCLUSION: In line with many epidemiological data, in the whole period 2003-2017, we observed a trend towards increase or decrease in incidence and periods of relative stability. Similar temporal heterogeneity with the comparison to our previous works was found.

Multiple Sclerosis in Italy: A 40-Year Follow-Up of the Prevalence in Ferrara.

BACKGROUND: To assess a longitudinal follow-up of the prevalence of multiple sclerosis (MS) through 4 decades in the province of Ferrara, northern Italy, and reappraise the current rates on December 31, 2016. METHODS: We conducted a community-based intensive prevalence study, by adopting a complete enumeration approach. MS cases were identified from administrative health data and medical records from the Units of Neurology and Motor Rehabilitation, Ferrara University Hospital, from other provincial neurological structures and from archives of the National Pension Institute and National Health Insurance scheme of the study area. Case ascertainment method and case definition are analogous to those adopted in previous surveys in the same area of study. RESULTS: On December 31, 2016, 685 patients (478 women and 207 men) affected by definite or probable MS (Poser's criteria) were living in the province of Ferrara (population 386,896), yielding a crude prevalence ratio of 194.91 (95% CI 180.4-209.6) per 100,000, 260.8 (95% CI 238.10-285.82) for women and 123.1 (95% CI 106.98-141.21) for men The prevalence ratio was 26.9 per 100,000 in 1978, increased to a value of 46.1 per 100,000 in 1981, 69.4 per 100,000 in 1993, 120.9 per 100,000 in 2004. Female to male ratio was 2.31 (1.2 on December 31, 1978). The mean duration of the disease at prevalence day was 17.5 ± 11.9 years (13.9 ± 10.8 years in 1978). The mean age at prevalence day was 52.04 ± 10.8 years (13.8 ± 10.8 years in 1978). CONCLUSION: Our study has confirmed the province of Ferrara is an area at high risk for MS, in line with epidemiological data from the regions of continental and insular Italy. The sharp increase in MS prevalence over time in this population can be imputed in part to a greater exposition to risk factors in genetically susceptible subjects but also to an increased survival and improved ascertainment. So, the results suggest that both methodologic and environmental factors are essential in determining the real distribution of MS. The need to get reliable estimates of MS prevalence must be highlighted as a public health and research priority, essential to support planning and prioritization of care services and to reduce the overall burden of chronic disease.

The urgent neurological consultation in the population of the province of Ferrara, Italy.

In the province of Ferrara, Italy, the urgent neurological consultation (UNC) cases in the population correspond to the resident outpatients who undergo a UNC in the ER of the university hospital of Ferrara (UHFe). Thanks to this health organization a retrospective survey identified 612 UNC cases (range of age 7-102 years, median 67,5 years) in the study period giving a period prevalence rate of 173 per 100,000 (95% CI 159.3-187.3) which increased with age (χ2 for trend = 178.4 p < 0.001). The daily UNC cases (range 0-14, mean = 7.3, 95% CI 7.1-7.5) followed the Poisson distribution (goodness-of-fit test: λ = 7.3, χ2 = 8082, 12 freedom degrees, p > 0.70). The prevalence rate decreased with the distance between the patients' residence and the UHFe (χ2 for trend = 82.9, p < 0.001). The commonest clinical conditions requiring UNCs were acute cerebrovascular disorders (28%), headache (14%), and vertigo (9%). The hospital admission rate was 32.5% which increased with age (χ2 for trend = 35.8, p < 0.001). The commonest discharge diagnoses of the admitted cases were ischemic stroke (57.3%), epilepsy (7%), TIA (6%), and intraparenchymal hemorrhage (5.5%). Acute cerebrovascular disease accounted for 69% of the discharge diagnoses. The survey showed that the UNCs' demand was higher than previous Italian data confirming that acute cerebrovascular disease is the most frequent acute neurological condition requiring attention in the ER. It also suggested that the UNCs could be poorly appropriate. These findings would require the healthcare administrators attention.

Multiple sclerosis in the Republic of San Marino, Italian peninsula: an incidence and prevalence study from a high-risk area.

Epidemiological studies on multiple sclerosis (MS) carried out in Southern Europe in the last years have shown a significant increase in the disease frequency. Previous surveys conducted in the Republic of San Marino, Northern Italian peninsula, identified that the population is at high risk for MS, with a prevalence of 51.6 per 100,000 population in 1982 and of 166.7 in 2005 and with a mean annual incidence of 7.9 per 100,000 for the period 1990-2005. The present work is a community-based intensive prevalence and incidence survey, by a complete enumeration approach, to update the prevalence and incidence of MS in the Republic of San Marino. The mean annual incidence for the period 2005-14 was 7.7 (95% CI 4.9-11.4) per 100,000, 3.3 (95% CI 1.1-7.6) for men and 11.9 (95% CI 7.2-18.6) for women. On 31 December 2014, 67 patients (19 men and 48 women), suffering from definite or probable MS and living in the Republic of San Marino, yielded a crude prevalence of 204.3 (95% CI 158.4-259.5) per 100,000, 117.8 (95% CI 70.9-183.7) for men and 288.2 (95% CI 212.4-383.3) for women. Our study has confirmed San Marino is an area at high risk for MS, in line with epidemiological data from continental Italy. The marked increase in MS prevalence over time in this population can be ascribable to increased survival and improved ascertainment, in the presence of a substantially stable, yet high, incidence rate.

Epidemiological Study of Huntington's Disease in the Province of Ferrara, Italy.

BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by the abnormal expansion of CAG triplet repeat. We aimed to reappraise HD epidemiology in a northern Italian population, in relation to introduction of genetic testing. METHODS: Through ICD-9M code 333.4 and medical fare exemption code RF0080, HD cases were identified from administrative health data and medical records from the Units of Neurology and Genetics, Ferrara University Hospital, and from other provincial neurological structures. RESULTS: HD mean annual incidence rate in 1990-2009 was 0.3 per 100,000 (95% CI 0.2-0.5). All incident cases were found to have symptoms of the disease's classic form, and neither juvenile nor the rigid Westphal variant was detected. The mean (SD) age at onset was 50.2 (12.7 years; range 32-82 years), 54.9 (14.6) for men and 45.8 (9.4) for women. On prevalence day, December 31, 2014, HD prevalence was 4.2 per 100,000 (95% CI 2.4-7.0), with a male:female ratio of 1:2. CONCLUSIONS: The prevalence and incidence of HD in our population were lower than the prevalence and incidence reported for other European and Italian populations, but higher compared to those of Asia, Africa, and Eastern Europe. Compared to previous studies, HD incidence and prevalence did not change significantly.

Can the age at onset give a clue to the pathogenesis of ALS?

Pathogenesis could play an important role in the mid- to late-life onset of symptoms in amyotrophic lateral sclerosis (ALS). An analysis of the age at onset of ALS among the incident cases occurring in the population in the Health District of Ferrara, Italy, in the period 1064-2009 was carried out. Two subsequent 23-year time intervals (1964-1986 and 1987-2009) were considered. The mean age at onset (MAAO) was estimated in relation to gender, onset type and area of residence (urban or extra-urban) at disease onset among the incident cases which occurred in the two subsequent time intervals. An uneven increase in the MAAO over time was observed as it was significant only among the female cases (from 56.7 95 % CI 51.6-61.7 years to 65.4 95 % CI 61.8-69.0 years), the overall bulbar onset cases (from 58.0 95 % CI 54.0-62.1 years to 69.3 95 % CI 66.2-72.4 years), the overall cases occurring in the extra-urban population (from 54.5 95 % CI 49.0-60.1 years to 65.1 95 % CI 60.4-69.8 years) and the bulbar onset cases occurring in the extra-urban population (from 57.1 95 % CI 53.5-60.7 years to 69.6 95 % CI 66.3-73.7 years). Although the increasing age of the population combined with improvements in ALS diagnosis among the elderly may have played a part, these uneven findings among the incident cases occurring in a well-defined homogeneous population with a stable ALS incidence would seem to suggest the involvement of risk factors associated with the extra-urban environment.

Temporal trend of amyotrophic lateral sclerosis incidence in southern Europe: a population study in the health district of Ferrara, Italy.

Data about the temporal trend of amyotrophic lateral sclerosis (ALS) incidence in southern Europe are scarce. Incidence studies on ALS have been carried out in the health district of Ferrara, Italy, since 1960s. We expanded the previous studies from 1964 to 2009. The study was prospective with a subsequent retrospective intensive survey of multiple sources of case ascertainment. All patients with a definite and probable ALS according to the original El Escorial criteria were selected. There were 130 incident cases in the years 1964-2009 giving an average annual crude incidence of 1.82 per 100,000 population (95% CI 1.53-2.17). An incidence increase during the study period was estimated in women (χ(2) test for trend = 7.19, p < 0.01) and in the elderly (χ(2) test for trend = 7.803, p < 0.01). The age-adjusted incidence was stable over time in both women (1.19 per 100,000, 95% CI 0.90-1.52) and men (1.45 per 100,000, 95% CI 0.12-1.84). The annual number of new ALS cases in the study population followed the Poisson distribution in both sexes as well as in the elderly group of the population. The present findings suggest that ALS incidence is nearly stable over time. The crude incidence increase we estimated over time among women is mainly explained by population ageing. The increasing incidence in the elderly population was likely the consequence of an increasing precision in ALS diagnosis in the elderly since the increasing attention and care over time of neurologic elderly patients that likely concern elderly women more than previous time periods rather than better case ascertainment of diagnosed patients. The present findings do not support the role of specific environmental factors in ALS pathogenesis.

An autopathography of tic douloureux at the beginning of the nineteenth century.

An Italian lawyer who suffered from tic douloureux wrote an autopathography of his disease documenting a 2-decade history of essential trigeminal neuralgia. The diary reveals a medical history from onset until 1823 when this man was admitted to the Arcispedale Sant'Anna in Ferrara. The documentation was recently discovered in the library of the hospital where it was probably placed when the patient died in 1824. Mr. Ruggiero Ragazzi was a man of notable culture who described the course of his disease and the most accredited treatments of that age. Famous Italian physicians examined and treated the patient. Prescriptions, suggestions, letters were attached to the manuscript as well as other notes on treatments for this type of chronic and recurrent pain. Autopsy excluded secondary neuralgias. Information on clinical and pathogenetic theories about trigeminal neuralgia and the state of diagnostics and therapies in the first years of the nineteenth century are reported.

Gender differences in health-related quality of life in multiple sclerosis.

Women have about twice the risk of developing multiple sclerosis (MS) compared with men, a ratio that seems to be increasing. Most studies show that female patients seem to have a more favourable outcome of the disease. We studied the gender-specific impact of MS on health-related quality of life. We surveyed the population prevalence of MS patients in Ferrara, Italy. Data were extracted from the MS registry of the study area. Health-related quality of life was assessed using the MSQOL54 questionnaire. We analysed 370 patients (105 men and 265 women). They had worse scores than the general population in all health-related quality of life dimensions, ranging from 2.5 standard deviations (SD) lower for physical functioning to less than 0.5 standard deviations for mental health. Health-related quality of life scores were inversely correlated with disability scores. The impact of disability on health-related quality of life was higher for men than women regarding physical functioning (p < 0.01), vitality (p < 0.001), social functioning (p < 0.001), emotional wellbeing (p < 0.05) and mental health (p < 0.01). For scales reflecting mental health, a marked reduction with increasing disability was seen for men, while a linear reduction in the range of Expanded Disability Status Scale score 0-5 was reported for women, followed by no clear decrease for higher scores. We conclude that MS affects health-related quality of life in all of its dimensions. The impact of disability seems to be stronger among men, in particular for scales related to mental well-being. This could indicate that interventions should to be gender specific in order to better meet patients' needs.

Novel mitochondrial tRNA Leu(CUN) transition and D4Z4 partial deletion in a patient with a facioscapulohumeral phenotype.

Point mutations in mtDNA-encoded tRNA genes frequently cause isolated myopathies but rarely cause the facioscapulohumeral phenotype. We report on a patient affected with chronic progressive weakness of facioscapulohumeral/peroneal muscles whose muscle biopsy showed a mitochondrial myopathy. mtDNA direct sequencing and RFLP analysis revealed a heteroplasmic transition T12313C which disrupts a conserved site in the T Psi C stem of the tRNA(Leu(CUN)) gene and fulfills the accepted criteria of pathogenicity. A partial deletion of the nuclear DNA D4Z4 region with residual repeat sizes of 25 kb was also found in the patient and in her mother. This is the first reported case of mitochondrial myopathy/facioscapulohumeral muscular dystrophy (FSHD) "double trouble".

Incidence of status epilepticus in southern Europe: a population study in the health district of Ferrara, Italy.

BACKGROUND: The epidemiologic features of status epilepticus (SE) are still in the course of definition. METHODS: We carried out an intensive survey of multiple sources of case material in the resident population of the health district of Ferrara, Italy, in 2003. Information was collected on age, gender, duration, seizure type and etiology of SE. RESULTS: The age- adjusted annual incidence rate of SE was 27.2/100,000 (95% CI = 19.4-36.9) and it was higher in men (41.7/100,000, 95% CI = 26.9-61.7) than in women (12.3/100,000, 95% CI = 6.9-20.4). The incidence was higher in the elderly (older than 60 years, 39.2/100,000) than in younger adults in the age group 20-59 years (14.7/100,000). The age-specific incidence showed a bimodal distribution peaking in the youngest (0-4 years) and in the oldest age group (75+ years). Cerebrovascular disease was the most frequent etiologic factor (45%). Epilepsy had previously been diagnosed in 40% of the patients. The case fatality was 5%. CONCLUSIONS: The study found a higher incidence of SE than that expected on the basis of the previous European studies suggesting that the risk of SE in southern Europe is higher and more similar to that estimated in population studies in the United States. The case fatality was lower than that reported in previous South-European population studies despite the similar clinical features of the patients. Indirect evidence suggests that several factors related to the SE management could have positively influenced the outcome.

Amyotrophic lateral sclerosis, rural environment and agricultural work in the Local Health District of Ferrara, Italy, in the years 1964-1998.

Previous epidemiological surveys, both analytic and descriptive, in the Local Health District (LHD) of Ferrara, northern Italy, have indicated that rural residence and agricultural work might constitute risk factors for Amyotrophic Lateral Sclerosis (ALS). The present investigation is a demographic survey in the LHD of Ferrara in the years 1964-1998 which aimed to verify whether the level of urbanization and agricultural activities might influence the risk of ALS. Based on the data obtained in a recent incidence study in the LHD of Ferrara which reported a mean annual crude incidence rate of ALS in the years 1964-1998 of 1.63 per 100,000 population (95 % CI 1.31-2.00), it was possible to compare the number of observed ALS cases and the number of expected ALS cases according to the level of urbanization and usual occupation on the basis of the residential and occupational pattern identified in the population of the LHD of Ferrara in the study period under the assumption of a homogeneous distribution of ALS. The present survey identified four different levels of urbanization in the LHD of Ferrara in the study period and for none of them was a difference between the number of observed and expected ALS cases found. Also in the most rural of the four identified levels of urbanization (small villages with an average population in the study period lower than 1,000 inhabitants and scattered houses in the countryside) no difference was found between observed and expected number of ALS cases (observed ALS cases 16, 95% Poisson CI 9.1-25.9, expected ALS cases 18.3). Based on the occupational pattern identified in the population of the LHD of Ferrara in the study period the number of incident cases of ALS whose usual occupation was in agricultural work exceeded the expected number (observed ALS cases 22, 95% Poisson CI 13.8-32.3, expected ALS cases 6.0). The present findings indicate that rural residence itself does not influence the risk of ALS while agricultural activities could influence the risk of ALS, with occupational exposure to agricultural chemicals playing a possible role.

Pregnancy as a risk factor for restless legs syndrome.

Pregnant women have at least two or three times higher risk of experiencing restless legs syndrome (RLS) than the general population. These data come from few epidemiological studies finding an 11-27% prevalence of RLS during pregnancy. Women affected by pre-existing RLS often complain of worsening symptoms during pregnancy. This is usually a benign form of RLS, with the highest degree of severity in the third trimester and a tendency to disappear around delivery. The causes of the association between RLS and pregnancy are unknown. The most debated hypotheses are: metabolic alterations, with particular regard to iron and folate deficiency; hormonal influences related to the increase of prolactin, progesterone and estrogens during late pregnancy; and the changing motor habits and psychological state of pregnant women. The importance of folate and iron supplementation during pregnancy in preventing RLS is unclear. RLS in pregnant women is frequently unrecognized; they are often worried about the symptoms and do not receive an adequate explanation by doctors.

Beneficial effect of interferon-beta 1b treatment in patients with relapsing-remitting multiple sclerosis is associated with an increase in serum levels of soluble HLA-I molecules during the first 3 months of therapy.

It has recently become clear that interferon-beta (IFN-beta) treatment is effective in ameliorating relapsing-remitting multiple sclerosis (RRMS) through an as yet unidentified mechanism. As there is no recognisable biological indicator to predict responsiveness to IFN-beta treatment, we have investigated fluctuations in serum sHLA-I levels in MS patients undergoing IFN-beta 1b therapy. Serum sHLA-I concentrations measured by enzyme-linked immunosorbent assay (ELISA) were assessed at baseline and, longitudinally, over a period of 18 months after the start of treatment in 29 RRMS patients grouped as responders and nonresponders according to their clinical response to IFN-beta 1b therapy. Thirty-nine healthy volunteers served as controls. Serum sHLA-I concentrations were significantly higher (p<0.001) in pretreated RRMS patients than in healthy donors. In MS patients, changes in mean serum levels of sHLA-I from baseline showed a temporal pattern characterized by a strong increase in the first trimester of treatment, a return toward basal values in the following 6 months, a slight decline at 12th and 15th months and a further moderate increase at the 18th month. Mean serum sHLA-I levels were significantly more elevated in responders than in nonresponders at the first (p<0.02), second (p<0.01), and at third (p<0.02) months after the beginning of treatment and significantly lower (p<0.01) at the time of relapses in comparison to baseline values. Overall, these results seem to indicate that IFN-beta 1b can modulate fluctuations in serum sHLA-I levels and argue in favour of a potential role for serum levels of sHLA-I as a sensitive marker to monitor response to IFN-beta treatment in MS.

Is there a decrease in Guillain-Barré syndrome incidence after bovine ganglioside withdrawal in Italy? A population-based study in the Local Health District of Ferrara, Italy.

There have been many reports of cases of Guillain-Barré syndrome (GBS) after therapeutic injection of bovine ganglioside preparations with the result that they were withdrawn in Italy in December 1993. As the relationship between bovine gangliosides and GBS has not yet been established, a further epidemiological investigation in the Local Health District (LHD) of Ferrara, Italy, was carried out in the years 1994-2001 to verify whether the incidence of GBS had changed after ganglioside withdrawal. The other aim of this investigation was to update the incidence of GBS in this area since the two previous investigations we carried out showed an increase in incidence from the years 1981-1987 to the years 1988-1993. The cases of GBS were identified prospectively. To guarantee completeness of case ascertainment, an intensive retrospective survey of all possible sources of cases for the entire study period was performed. The mean annual crude incidence rate in the years 1994-2001 (based on 26 new cases) was 1.97 per 100,000 population (95% CI 1.29-2.89), whereas it had been 1.87 per 100,000 population (95% CI 1.35-2.52) in the years 1981-1993 (based on 43 cases) when gangliosides were available. The age-adjusted rates were almost identical (1.66 and 1.65 per 100,000 population, respectively). Although ganglioside administration could have triggered, on the basis of an individual susceptibility, an immunologic reaction which produced GBS, the incidence of GBS in the study area did not change after ganglioside withdrawal. In the whole period 1981-2001, a temporal pattern of incidence was reported with an increase towards a peak in 1990-1992 and a progressive decline thereafter. This temporal pattern did not seem related to ganglioside withdrawal, and no definite explanation for it was found which could imply that the disease incidence is less stable than it was deemed.