Very Early Carotid Endarterectomy After Intravenous Thrombolysis.

OBJECTIVE/BACKGROUND: The timing of carotid endarterectomy (CEA) after thrombolysis is still a matter of debate. The aim of this study was to analyse a cohort of patients undergoing urgent endarterectomy after intravenous thrombolysis for acute ischaemic stroke. METHODS: This was an observational study. Prospective databases were reviewed and matched to identify patients who underwent CEA early after intravenous thrombolysis (2009-14). The focus was carotid surgery performed within 12 hours of stroke onset in patients with a high grade (≥70%) symptomatic carotid stenosis, associated with vulnerable plaques or stroke in evolution, and evidence of a significant salvageable ischaemic penumbra on perfusion computed tomography scan. Demographic and clinical information, as well as data on relevant outcomes were extracted. RESULTS: Thirty four consecutive stroke patients who underwent CEA within 2 weeks of thrombolysis for acute ischaemic stroke and ipsilateral high grade carotid stenosis were identified. In 11 patients the surgical procedure was performed within 12 hours of the onset of symptoms. All patients showed a clinical improvement after combined treatment. The 3 month outcome was favourable (modified Rankin Scale ≤ 2) in 10 patients. No haemorrhagic complications were registered. There was neither peri-operative stroke nor stroke within 3 months of surgery. One patient died from acute myocardial infarction 3 days after intervention. CONCLUSION: This experience suggests that very early CEA after thrombolysis, aimed at removing the source of potential embolisation and restoring blood flow, may be safe and can lead to a favourable outcome.

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.

A(2A) adenosine receptors and Parkinson's disease severity.

OBJECTIVES: In the last decade, increasing evidence suggests a key role of adenosine in Parkinson's disease (PD) and A2A adenosine receptors (A2A ARs) as an important pharmacological target in PD. An overexpression of A2A ARs has been found in putamen and in peripheral blood cells of PD patients. The primary aim of this study was to verify whether the alterations in A2A ARs in lymphocytes of PD subjects correlate with disease severity. MATERIAL AND METHODS: A consecutive sample of PD patients was enrolled. A clinical examination and a face-to-face interview were carried out. A2A ARs were investigated to verify the affinity and receptor density in lymphocyte membranes. The data were compared with those found in healthy controls. Moreover, the correlation between A2A AR density and affinity and clinical variables was evaluated in PD patients. RESULTS: In human lymphocyte membranes from PD patients, an increase in A2A AR density and a decrease in A2A AR affinity were found if compared with healthy subjects. A statistically significant correlation between the A2A AR density or affinity and specific clinical parameters as motor and cognitive impairment was detected. Patients with higher A2A AR density and lower affinity were more likely to exhibit motor complications. CONCLUSIONS: Parkinson's disease patients show an A2A AR upregulation in lymphocyte membranes if compared with healthy subjects. The correlation found between A2A AR density or affinity and clinical parameters highlights the central role of A2A AR modulation in the pharmacological treatment for PD and could suggest the putative role of A2A AR as a candidate biomarker of PD severity.

Outcomes with Endovascular Treatment of Patients with M2 Segment MCA Occlusion in the Late Time Window.

BACKGROUND AND PURPOSE: Randomized trials in the late window have demonstrated the efficacy and safety of endovascular thrombectomy in large-vessel occlusions. Patients with M2-segment MCA occlusions were excluded from these trials. We compared outcomes with endovascular thrombectomy in patients with M2-versus-M1 occlusions presenting 6-24 hours after symptom onset. MATERIALS AND METHODS: Analyses were on pooled data from studies enrolling patients with stroke treated with endovascular thrombectomy 6-24 hours after symptom onset. We compared 90-day functional independence (mRS ≤ 2), mortality, symptomatic intracranial hemorrhage, and successful reperfusion (expanded TICI = 2b-3) between patients with M2 and M1 occlusions. The benefit of successful reperfusion was then assessed among patients with M2 occlusion. RESULTS: Of 461 patients, 367 (79.6%) had M1 occlusions and 94 (20.4%) had M2 occlusions. Patients with M2 occlusions were older and had lower median baseline NIHSS scores. Patients with M2 occlusion were more likely to achieve 90-day functional independence than those with M1 occlusion (adjusted OR = 2.13; 95% CI, 1.25-3.65). There were no significant differences in the proportion of successful reperfusion (82.9% versus 81.1%) or mortality (11.2% versus 17.2%). Symptomatic intracranial hemorrhage risk was lower in patients with M2-versus-M1 occlusions (4.3% versus 12.2%, P = .03). Successful reperfusion was independently associated with functional independence among patients with M2 occlusions (adjusted OR = 2.84; 95% CI, 1.11-7.29). CONCLUSIONS: In the late time window, patients with M2 occlusions treated with endovascular thrombectomy achieved better clinical outcomes, similar reperfusion, and lower symptomatic intracranial hemorrhage rates compared with patients with M1 occlusion. These results support the safety and benefit of endovascular thrombectomy in patients with M2 occlusions in the late window.

Incidence of childhood and adolescence epilepsy: a community-based prospective study in the province of Ferrara and in Copparo, Italy, 1996-2005.

BACKGROUND: The annual incidence of childhood and adolescence epilepsy ranges from 41 to 97 diagnoses per 100,000 people in western Countries, with a reported decline over time. We aimed at studying the incidence of epilepsy in children and adolescents (1 month to 14 years) and its temporal trend in the province of Ferrara, northern Italy. METHODS: We implemented a community-based prospective multi-source registry. All children with newly diagnosed epilepsy in the period 1996-2005 were recorded. RESULTS: The incidence rate of newly diagnosed epilepsy in the considered age range was 57 per 100,000 person-years, (95% CI: 49.3-65.9), with a peak in the first year of life (109.4; 95% CI: 69.4-164.1), without differences between the two gender. The estimates were significantly lower than those observed previously (97.3; 95% CI: 81.9-115.7). CONCLUSIONS: Incidence rates for epilepsy in the Italian population aged 1 month to 14 years are in line with those of other European and Northern American Countries. The incidence of childhood epilepsy has declined over time in our area. A reduced impact of serious perinatal adverse events could partly explain the decline.

Intrathecal levels of vitamin D and IgG in multiple sclerosis.

BACKGROUND: Intrathecal synthesis of IgG is a hallmark of multiple sclerosis (MS). Vitamin D may modulate B-cell function and dampen the synthesis of IgG. OBJECTIVE: To investigate the relation between vitamin D levels in cerebrospinal fluid and serum and intrathecal synthesis of IgG. METHODS: 25-hydroxyvitamin D (25(OH)D) and IgG were assessed in cerebrospinal fluid and serum in 40 patients with MS. RESULTS: There was no significant correlation between the IgG index and 25(OH)D levels in cerebrospinal fluid or serum. The levels of 25(OH)D in cerebrospinal fluid and serum did not differ between patients with and without intrathecal synthesis of IgG. There was a non-significant trend towards a positive correlation between the concentrations of 25(OH)D and IgG in the cerebrospinal fluid, but not in serum. CONCLUSION: Physiological variation in vitamin D does not exert a major impact on intrathecal synthesis of IgG in MS.

Prevalence of self-reported symptoms related to temporomandibular disorders in an Italian population.

The aim of this study was to estimate the prevalence of temporomandibular disorders (TMD) symptoms in an Italian population sample, focusing on gender and age differences. We selected 2005 individuals by telephone survey and asked them about TMD symptoms like difficulty in jaw movement, jaw pain and joint sounds. Also, tooth-clenching and/or tooth-grinding habits were investigated. Of the study population, 8·1% reported limitations in jaw movements, 5·1% reported jaw pain and 33·3% reported joint sounds. Furthermore, 37·3% reported tooth-clenching/tooth-grinding. Confidence intervals of proportions were calculated. Significant gender differences were found for jaw limitation and pain (chi-square test; P < 0·05). Symptoms reduced with increasing age. The prevalence of TMD symptoms in the Italian population was consistent with data reported from similar studies. Gender and age differences were found for jaw pain and limitation in jaw movements.

Azathioprine for multiple sclerosis.

BACKGROUND: Azathioprine (AZA) is an immunosuppressive drug widely prescribed for the treatment of multiple sclerosis (MS) until the first half of the 1990s. It could be an alternative to interferon beta because it is less expensive. Concerns about its safety, mainly a possible increased risk of malignancy, have been raised. This systematic review aimed to determine the trade off between the benefits and risks of azathioprine in MS. OBJECTIVES: To compare azathioprine with placebo. To assess the effect of azathioprine on major clinical outcomes (ie, disability progression and relapses) in patients with MS, and to evaluate the drug's safety. METHODS: The Cochrane MS Group search strategy was adopted to identify relevant articles. All randomised controlled trials comparing azathioprine treatment of a least 1 year duration with placebo for patients with MS were eligible for the review. Cohorts, case controls, case series and case reports were also considered to assess adverse effects. Regulatory agencies were additional sources of information for adverse effects. More details are available in the full review.

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.

Azathioprine for multiple sclerosis.

BACKGROUND: Azathioprine is the most widely used immunosuppressive treatment in multiple sclerosis (MS). It is an alternative to interferon beta for treating MS also because it is less expensive. Concerns about its safety, mainly a possible increased risk of malignancy, has limited its use. This systematic review aimed to determine the trade off between the benefits and risks of azathioprine in multiple sclerosis. OBJECTIVES: To compare azathioprine versus placebo. To determine the effect of azathioprine on major clinical outcomes, i.e., disability progression and relapses in patients with multiple sclerosis. SEARCH STRATEGY: The Multiple Sclerosis Group's Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL- Issue 4, 2006), Cochrane Database of Systematic Reviews (CDSR - Issue 4, 2006), Database of Abstracts of Reviews of Effectiveness (DARE - searched 28.12.06) MEDLINE (PubMed) (1966 to December 2006), EMBASE (1980 to December 2006). Journals and reference lists were hand searched for relevant articles both to benefit and adverse effects. Regulatory agencies were additional sources of information for adverse effects. SELECTION CRITERIA: All parallel group randomised controlled trials (RCTs) comparing azathioprine treatment of a least one year duration with placebo for patients with multiple sclerosis. Cohorts, case controls, case series and case reports were also used to assess adverse effects. DATA COLLECTION AND ANALYSIS: Potentially relevant references were evaluated and all data extracted by two independent authors. MAIN RESULTS: The five trials that met our criteria included 698 randomised patients: data from 499 (71.5%) were available for analysis of relapse frequency in patients at one year's, from 488 (70%) at two years' and from 415 (59.5%) at three years' follow-up. Azathioprine reduced the number of patients who had relapses during the first year of treatment (relative risk reduction [RRR] =20%; 95% CI = 5% to 33%), at two years' (RRR =23%; 95% CI = 12% to 33%) and three years' (RRR =18%; 95% CI = 7% to 27%) follow-up. These results were consistent in sensitivity analysis. There was no heterogeneity among the studies. Data from only three small trials with a total of 87 patients were available to calculate the number of patients who progressed during the first two to three years. There was a statistically significant benefit (RRR = 42%; 95% CI = 7% to 64%) of azathioprine therapy at three years' follow-up; this result was robust after sensitivity analyses and there was no heterogeneity among the trials. Gastrointestinal disturbances, bone marrow suppression and hepatic toxicity were greater in the azathioprine group rather than in the placebo group; they were anticipated, and, by monitoring and dosage adjustment, were easily managed. Withdrawals due to adverse effects were few, occurring mostly during the first year of azathioprine treatment and mainly due to gastrointestinal intolerance (5%). Data from the trials and from cohort and case controls studies available in the literature did not show an increase in risk of malignancy from azathioprine. A possible long-term risk of cancer from azathioprine may be related to a treatment duration above ten years and cumulative doses above 600 g. AUTHORS' CONCLUSIONS: Azathioprine is an appropriate maintenance treatment for patients with multiple sclerosis who frequently relapse and require steroids. Cumulative doses of 600 g should not be exceeded in relation to a possible increased risk of malignancy. Considering the trade off between the benefits and harms, azathioprine is a fair alternative to interferon beta for treating multiple sclerosis. A logical next step for future trials would seem the direct comparison of azathioprine and interferon beta. In fact the direct comparison between these two widely used treatments in multiple sclerosis has not been made.

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.

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.

A questionnaire for multinational case-control studies of environmental risk factors in multiple sclerosis (EnvIMS-Q).

OBJECTIVES: The increasing incidence of multiple sclerosis (MS) worldwide, especially in women, points to the crucial role of environmental and lifestyle risk factors in determining the disease occurrence. An international multicentre case-control study of Environmental Risk Factors In Multiple Sclerosis (EnvIMS) has been launched in Norway, Sweden, Italy, Serbia and Canada, aimed to examine MS environmental risk factors in a large study population and disclose reciprocal interactions. To ensure equivalent methodology in detecting age-related past exposures in individuals with and without MS across the study sites, a new questionnaire (EnvIMS-Q) is presented. MATERIALS AND METHODS: EnvIMS-Q builds on previously developed guidelines for epidemiological studies in MS and is a 6-page self-administered postal questionnaire. Participants are de-identified through the use of a numerical code. Its content is identical for cases and controls including 'core' and population-specific questions as proxies for vitamin D exposure (sun exposure, dietary habits and supplementation), childhood infections (including infectious mononucleosis) and cigarette smoking. Information on possible confounders or effect modifiers is also obtained. EnvIMS-Q was initially drafted in English and subsequently translated into Italian, Serbian, Norwegian, Swedish and French-Canadian. EnvIMS-Q has been tested for acceptability, feasibility and reliability. RESULTS AND CONCLUSIONS: EnvIMS-Q has shown cross-cultural feasibility, acceptability and reliability in both patients with MS and healthy subjects from all sites. EnvIMS-Q is an efficient tool to ensure proper assessment of age-specific exposure to environmental factors in large multinational population-based case-control studies of MS risk factors.

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.

Myasthenia gravis: a changing pattern of incidence.

The annual incidence of myasthenia gravis (MG) ranges from 3 to 30 per 1,000,000 people. Since the mid-1980s, an increasing incidence has been reported, mainly due to late-onset MG. Whether the increase was due to population aging, improved diagnosis and case collection, or a true excess of incidence cases is still under debate. We used a complete enumeration approach by reviewing all possible sources of case collection in the province of Ferrara, Italy, to estimate the MG incidence and its temporal trend over the study period (1985-2007). The mean annual age-adjusted incidence of MG was 18 per 1,000,000, without any significant temporal trend. The incidence rates in the period 1985-1990 were 14 both for early and late-onset MG. Thereafter, a significant increase in incidence of late-onset MG (p < 0.05), and a decrease in early onset MG were detected (p < 0.01). These findings were related to nonthymoma MG. The median age at onset of the disease steadily increased over time. A changing pattern of MG incidence with an increase in frequency of late-onset and a decrease of early onset MG was found in the last years, giving a significant shift to older age at onset of the disease. Unknown environmental factors may have driven this change in MG epidemiology.