Space-time distribution of the ALS incident cases by onset type in the Health District of Ferrara, Italy.

OBJECTIVES: An ecological study in the resident population of the Health District (HD) of Ferrara, Italy, has been carried out to establish the distribution in space and time of the amyotrophic lateral sclerosis (ALS) incident cases according to the disease onset type and gender in the period 1964-2009. MATERIAL AND METHODS: The hypothesis of a uniform distribution was assumed. RESULTS: The incident cases of spinal onset ALS and bulbar onset ALS were evenly distributed in space and time in both men and women. The spinal onset ALS incident cases distribution according to gender was significantly different from the expected in the extra-urban population (20 observed cases in men 95% Poisson confidence interval 12.22-30.89, expected cases in men 12.19; six observed cases in women 95% Poisson confidence interval 2.20-13.06, expected cases in women 13.81), whereas no difference was found in the urban population. The spinal onset ALS incidence was higher in men than in women in the extra-urban population (difference between the rates = 1.53, 95% CI associated with the difference 0.52-2.54), whereas no difference between sexes was found in the urban population. CONCLUSIONS: The uneven distribution according to gender of the spinal onset ALS incident cases only in the extra-urban population suggests the involvement of a gender related environmental risk factor associated with the extra-urban environment. Despite some limits of the spatial analysis in the study of rare diseases, the results appear consistent with the literature data.

Sudden hearing loss and the risk of subsequent cerebral ischemic stroke.

OBJECTIVE: Very few studies have investigated the risk of ischemic stroke after an episode of sudden sensorineural hearing loss (SSNHL), and findings have been controversial. The aim of this study was to estimate the risk of ischemic stroke among SSNHL patients within the province of Ferrara and compare the findings with data available in the literature. METHODS: This was a cohort study using hospital discharge records. The observation period was from 1 January 2001 to 31 December 2012. The study cohort consists of all adult patients hospitalized with a principal diagnosis of SSNHL (n = 484) and all adult patients with a diagnosis of ischemic stroke (n = 9985) among the resident population of the province of Ferrara, Emilia-Romagna, Italy. We calculated the incidence of SSNHL and ischemic stroke, as well as the incidence of ischemic stroke within the group of patients who experienced SSNHL. RESULTS: During the period 2001-2012 in Ferrara, the average annual crude incidence of SSNHL was 11.4/100,000 (95% CI 10.4-12.4), while the average annual crude incidence of the first ischemic stroke was 235.3/100,000. During the mean observation time period of 6 years, the expected and observed cases of ischemic stroke among the 484 patients with SSNHL did not differ significantly (6.8 expected vs. 9 observed [95% Poisson Confidence Interval 4.11-17.08]). CONCLUSIONS: Our findings suggest that SSNHL does not significantly increase the risk of ischemic stroke.

Multiple sclerosis in the province of Ferrara : evidence for an increasing trend.

BACKGROUND: Epidemiological studies on the distribution of multiple sclerosis (MS) conducted in the Mediterranean area in the last two decades have disclosed a significant increase in frequency of the disease, indicating caution when a latitude-related model of MS is accepted. Previous descriptive surveys in the province of Ferrara, northern Italy, carried out by our own epidemiological research group, have established that this area is at high risk for MS. OBJECTIVE: To confirm the above assumption and to update MS frequency estimates in this area. DESIGN AND SETTING: We conducted a community-based intensive prevalence and incidence study, by adopting a complete enumeration approach. RESULTS: On December 31, 2004, 423 patients (300 women and 123 men) suffering from definite or probable MS (Poser's criteria) living in the province of Ferrara, yielded a crude prevalence rate of 120.93 (95 % CI, 110.05-134.23) per 100,000, 164.26 for women and 73.59 for men. The average incidence from 1990 to 2003 was 4.35 per 100,000 (95 % CI, 3.77-4.99), 5.91 for women and 2.63 for men. The incidence rate,which was relatively stable during the previous 25 years (1965-1989) with a mean rate of 2.3 per 100,000, increased to a value of 3.39 per 100,000 in the period 1990-1994, 4.09 per 100,000 in the period 1995-1999 and 3.84 per 100,000 in the period 2000-2003. CONCLUSIONS: These results confirm that in Ferrara MS occurs more frequently than suggested by the geographic- related distribution model and, based on other recent national surveys, support the view that northern Italy is a high-risk area for the disease. The marked increase in MS prevalence rate, in comparison with previous investigations, is in part due to the increasing survival of patients as a result of improved supportive care and the accumulation of new incidence cases owing to the reduction in diagnostic latency for better quality of neurological diagnostic procedures. The incidence in the province of Ferrara was found to slowly change with an incremental trend,which cannot only be attributed to improvements in diagnostic ability. Environmental risk factors in genetically predisposed people over time could be considered.

Oxidative stress, antioxidants and neurodegenerative diseases.

It is widely accepted that oxidative stress increases with age, and that age is a major risk factor for several neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. An inbalanced overproduction of reactive oxygen species can induce neuronal damage, leading to neuronal death by necrosis or apoptosis. Antioxidants are consequently considered to be a promising approaches to neuroprotection. Although experimental data are consistent in demonstrating a neuroprotective effects of antioxidants in vitro and in animal models, the clinical evidence that antioxidants agents may prevent or slow the course of these diseases is still relatively unsatisfactory, and unsufficient to strongly modify the clinical practice. This review summarizes the available data from experimental studies and clinical trials on antioxidant neuroprotection in Parkinson's and Alzheimer's disease.

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.

The increasing incidence and prevalence of MS in a Sardinian province.

OBJECTIVE: To verify incidence rates and their temporal trend in a homogeneous, ethnically, and genetically distinct population of central Sardinia (the Nuoro province). BACKGROUND: Intensive epidemiologic studies carried out in Sardinia since the 1970s have suggested that the prevalence and incidence of MS are much higher in this Mediterranean island compared with those found on mainland Italy. METHODS: The study area had a population of approximately 274, 000 people in the 1991 census. The authors adopted a complete enumerative approach by reviewing all possible sources of case collection available in the investigative area. RESULTS: Based on 469 MS patients, the mean annual incidence for 1955 to 1995 was 4.18 per 100,000 (or 4.3 per 100,000 if age- and sex-adjusted to the European population). The incidence, averaging 1.95 per 100,000 during 1955 to 1959, rose progressively over time, reaching rates of 6.6 in the quinquiennium 1985 to 1989 and 6.4 per 100,000 in 1990 to 1995. On December 31, 1994, the crude prevalence, based on 415 MS patients alive in the study area, was 151.9 per 100,000 (156.6 if adjusted to the European population). CONCLUSION: These incidence and prevalence rates are the highest to date that have been estimated for a large community in southern Europe, and they constitute some of the highest rates in the world. Based on other surveys, these results reinforce the position of Sardinia as a higher and rising prevalence area for MS compared with other Mediterranean populations. Genetic and social-historic data strengthen the hypothesis of the environmental role and genetic factors among Sardinians in determining the notable difference in MS frequency between Sardinians and other Mediterraneans.

Assessment of HIV-intrathecal humoral immune response in AIDS-related neurological disorders.

Intrathecal synthesis of IgG directed to HIV antigens was investigated by antibody specific index (ASI), affinity-mediated immunoblot (AMI) and Western blot (WB) assay in a group of 88 AIDS patients of which 28 with HIV-associated neurological disorders (HAND), 13 without associated neurological disorders (WAND) and 47 with non-HIV-associated neurological disorders (non-HAND). CD4+ count was above 50 cells/mm3 (CD4+>50) in 30 and below 50/mm3 (CD4+<50) in 58 patients, respectively. A significantly higher frequency for CSF complete anti-gag profile (p<0.001), and for HIV-specific oligoclonal patterns ("mixed" pattern=p<0.01) was observed in HAND as compared to patterns from the other clinical groups. A decrease in complete anti-env, anti-pol and anti-gag reactivity was present in CSF of patients with CD4+<50 as compared to those with CD4+>50. Our findings suggest that AIDS appears to be characterized by an anti-HIV intrathecal humoral immune response which is principally directed to env products with a prevalence of oligoclonal patterns and CSF complete anti-gag profile in HIV-associated neurological involvement.

The frequency of clinical variants of Guillain-Barré syndrome in Ferrara, Italy.

As the available diagnostic criteria (National Institute of Neurological and Communicative Disorders and Stroke, NINCDS) for Guillain-Barré syndrome (GBS) do not permit inclusion of clinical variants (CV) of GBS, there are few data on their occurrence and few reports of the overall incidence of the disease. A population-based study in the local health district of Ferrara, Italy in 1981-1993 selected cases fulfilling both NINCDS criteria (NINCDS GBS cases) and CV. The incidence of CV was 0.35 per 100,000 person-years (95% CI: 0.15-0.68), 0.32 when age-adjusted to the Italian population. No difference was found between CV and NINCDS GBS for male/female ratio, mean age at onset, elevated CSF protein content, seasonal pattern, or mean time delay from first neurological symptom to maximal severity. A higher frequency of antecedent infections for CV and more frequent serious disease at the nadir time for NINCDS GBS were found. A complete recovery was more frequent for CV than NINCDS GBS, but no difference was found regarding good outcome (defined by a satisfactory recovery and resumption of normal functional life). Since most findings were similar for NINCDS GBS and CV cases, they may have similar underlying pathological mechanisms. When diagnostic criteria for GBS include CV, the overall disease incidence in the Ferrara district increases from 1.87 to 2.21 cases per 100,000 person-years (the contribution of CV to the overall incidence of GBS is 15.7%). The currently available diagnostic criteria for GBS, although useful for field studies, may be too restrictive as they can entail the loss of about 15% of cases.

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.

The history of the tic douloureux: autopathograph of an Italian lawyer who suffered from trigeminal neuralgia from 1803 to 1824.

In the years from 1803 to 1824 an Italian lawyer suffered from paroxysmal facial pain that resembled essential trigeminal neuralgia. He kept a diary of his disease from its onset until 1823 when he was admitted to the old Arcispedale S. Anna in Ferrara (St. Anna's Hospital), Italy. The diary was recently discovered in the library of the Arcispedale S. Anna where it was probably put when the patient died. The patient was a man of notable culture and was able to describe with great diligence not only the course of his disease but also the most accredited treatments of that age. Some of the most famous Italian physicians of the period (A.G. Testa, V.L. Brera, G.A. Tommasini, A. Scarpa) examined and treated the patient. Letters of theirs were attached to the manuscript as well as notes on several treatments for trigeminal neuralgia drawn from medical magazines of that age. A copy of the patient's autopsy was enclosed: it ruled out the possibility of secondary neuralgia. This manuscript gives us information on the clinical and pathogenetic theories about trigeminal neuralgia and the state of diagnostic and therpeutics in the first years of the nineteenth century.

Goniometric measurements of the forelimb and hindlimb joints in sheep.

OBJECTIVES: The aim of this study was to evaluate angle-of-motion values for the forelimb and hindlimb in clinically healthy adult Santa Ines sheep by means of a standard goniometer. METHODS: Twenty female Santa Ines sheep, ranging in age between three- to six-years-old, and weighing 32-45 kg (mean ± standard deviation [SD]: 30.4 ± 3.7) were used. A standard transparent plastic goniometer was used to measure passive maximum flexion, maximum extension, and range-of-motion (ROM) of the shoulder, elbow, carpal, hip, stifle, and tarsal joints in the right and left limbs. The goniometric measurements were done with the sheep awake and in a standing position. The measurements were made in triplicate by two independent investigators. RESULTS: In all evaluated joints, there was no significant difference either between the means of the two sides or between measurements performed by the two investigators. The mean ± SD values of the measurements (degrees) were as follows: 20 ± 1 (flexion), 170 ± 2 (extension), and 150 ± 2 (ROM) for the carpal joint; 34 ± 4 (flexion), 145 ± 6 (extension), and 110 ± 4 (ROM) for the elbow joint; 88 ± 2 (flexion), 144 ± 6 (extension), and 56 ± 5 (ROM) for shoulder joint; 35 ± 4 (flexion), 163 ± 3 (extension), and 129 ± 4 (ROM) for tarsal joint; 46 ± 4 (flexion), 146 ± 6 (extension), and 100 ± 4 (ROM) for the stifle joint; 54 ± 3 (flexion), 143 ± 7 (extension), and 89 ± 5 (ROM) for the hip joint. CLINICAL SIGNIFICANCE: The data obtained provide useful and objective information on the joints. More studies are necessary using other sheep breeds.

Transient RLS during pregnancy is a risk factor for the chronic idiopathic form.

OBJECTIVE: Pregnancy is a risk factor for transient restless legs syndrome, which usually recovers during the postdelivery period. The goal of the present survey is to investigate whether restless legs syndrome during pregnancy represents a risk factor for later development of restless legs syndrome. METHODS: A long-term follow-up study, planned as an extension of a previous survey on restless legs syndrome during pregnancy, was carried out. After a mean interval of 6.5 years, 207 parous women were contacted again to compare the incidence of restless legs syndrome among subjects who never experienced the symptoms with those who reported restless legs syndrome during the previously investigated pregnancy. RESULTS: Seventy-four women who experienced restless legs syndrome during previous pregnancy, and 133 who did not, were included in the study. The incidence of restless legs syndrome was 56% person/year in women who experienced the transient pregnancy restless legs syndrome form, and 12.6% person/year in subjects who did not, with a significant 4-fold increased risk of developing chronic restless legs syndrome in women who presented restless legs in the previous pregnancy. Considering further new pregnancies during the follow-up period, the restless legs symptoms reappeared in 58% of the cases, while they emerged for the first time in only 3% of women who had never experienced restless legs syndrome. CONCLUSIONS: The transient pregnancy restless legs syndrome form is a significant risk factor for the development of a future chronic idiopathic restless legs syndrome form, and for a new transient symptomatology in a future pregnancy.

Cerebral blepharoptosis: two new cases, literature review and proposal for diagnostic criteria.

Cerebral ptosis (CP) consists of acute and bilateral drooping eyelids due to a right or left middle cerebral artery territory stroke, without involvement of brain stem, third cranial nerve or oculosympathetic fibres. The pathogenesis of CP is still unknown, but most authors have hypothesised that eyelid control is hemispherically lateralised. Two new cases of CP and a complete literature review are reported in this paper. Because no unanimous criteria for CP diagnosis are currently available, a proposal for new criteria is also included.

Epidemiology of the Guillain-Barré syndrome.

This review focuses on recent epidemiological findings on Guillain-Barré syndrome regarding incidence, antecedent events related to the disease, prognosis and prognostic indicators, and treatment. Moreover, this review summarizes recent observations on clinical variants of Guillain-Barré syndrome and their relationship with the prevailing clinical presentation of the disease. The epidemiological observations which have advanced the understanding of the pathogenesis of Guillain-Barré syndrome are also discussed.

Incidence of the Guillain-Barré syndrome in Ferrara, northern Italy, 1981-1987.

The few incidence estimates on Guillain-Barré syndrome (GBS) in Italy indicate rates lower than the values provided by other previous non-Italian population-based studies. The latter range from 0.6 to 1.9 cases per 100,000 population per year. To verify whether Italy may be considered a low-risk area for GBS we studied the incidence of the disease in Local Health Unit No. 31 (USL 31) of Ferrara, Northern Italy (mean population 180,701 inhabitants) for the years 1981-1987. The annual incidence rates were stable during this period with an average incidence of 1.26 cases per 100,000 population per year. No significant difference was found for urban or rural residence and there was no significant seasonal clustering. In 37.5% of the series an antecedent infection was recorded within 4 weeks before GBS onset. The survey seems to support the hypothesis of a homogeneous distribution of GBS in space and time and does not support the notion that GBS is less common in Italy than elsewhere.

Incidence of myasthenia gravis in the province of Ferrara: a community-based study.

BACKGROUND: The reported annual incidence of myasthenia gravis (MG) ranges from 0.25 to 15 per million. The sex- and age-related pattern of disease incidence is still debated. METHODS: An intensive descriptive study was performed in the province of Ferrara (mean population 360,950 people) over the period 1985 through 2000. RESULTS: The average crude annual incidence rate was 2 per 100,000. We confirm a female preponderance in the total population, particularly in the youngest age groups. CONCLUSIONS: We observed an early increase in incidence in females, partly due to thymoma-associated MG, while MG without thymoma showed increasing incidence with age nonsignificantly different in the two sexes.