Vittorio Govoni

Restless legs syndrome and pregnancy

Objective: To perform a large and detailed epidemiologic study on restless legs syndrome (RLS) during pregnancy and the puerperium. Methods: A structured clinical interview, assessing symptoms since the beginning of pregnancy, was performed to a population of 642 pregnant women at the time of delivery and at follow-up evaluation (1, 3, and 6 months after delivery). Main hematologic tests were also evaluated. A woman was considered affected if she met the International RLS Study Group criteria for RLS diagnosis. Results: Twenty-six percent of women were affected by RLS during their pregnancy. The disease was strongly related to the third trimester of pregnancy and tended to disappear reaching the time of delivery. Affected women presented lower values of hemoglobin and mean corpuscular volume compared with healthy subjects (both groups received the same supplemental iron and folate therapy). Conclusions: Pregnancy is associated with transient restless legs syndrome.

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.

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.

Presence of detectable levels of soluble HLA-G molecules in CSF of relapsing–remitting multiple sclerosis: relationship with CSF soluble HLA-I and IL-10 concentrations and MRI findings

We have investigated the presence of non-classical soluble HLA-G molecules (sHLA-G) in cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients and the possible relationships between CSF levels of sHLA-G, classical soluble HLA-I (sHLA-I) molecules, IL-10 amounts and Magnetic Resonance Imaging (MRI) findings were evaluated. We studied by ELISA technique the sHLA-I, sHLA-G and IL-10 levels in CSF of 50 relapsing-remitting (RR) MS patients stratified according to clinical and MRI evidence of disease activity. Thirty-six patients with other inflammatory neurological disorders (OIND) and 41 with non-inflammatory neurological disorders (NIND) were used as controls. CSF mean levels were significantly higher in MS and OIND than in NIND for sHLA-I (p<0.001) and in MS than in controls for sHLA-G (p<0.001), with no differences among the various groups for IL-10 mean concentrations. An increase in CSF sHLA-I was found in MS patients with Gd-enhancing lesions (p<0.01), while sHLA-G and IL-10 were more represented in MS patients without lesional activity on MRI scans (p<0.02). In MRI-inactive MS, CSF IL-10 mean concentrations were significantly greater in patients with CSF-detectable levels of sHLA-G than in those without any evidence of CSF sHLA-G expression (p<0.05). Our findings suggest that CSF classical sHLA-I and non-classical sHLA-G levels may modulate MS activity as assessed by MRI acting in opposite directions. The association observed between sHLA-G and IL-10 when Gd-enhancing lesion resolved indicates a potential immunoregulatory role for IL-10 in the control of MS disease activity by shifting the sHLA-I/sHLA-G balance towards sHLA-G response.

A prospective study on the predictive value of CSF oligoclonal bands and MRI in acute isolated neurological syndromes for subsequent progression to multiple sclerosis.

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

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.

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.

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.

Ganglioside therapy and Guillain-Barré syndrome. A historical cohort study in Ferrara, Italy, fails to demonstrate an association.

We investigated an alleged association between ganglioside therapy and the risk of developing the Guillain-Barré syndrome (GBS) in a historical cohort study. Using official medical records of the Local Health Unit No. 31 of Ferrara Province, northern Italy, we linked data on sales of gangliosides with information regarding hospital admissions and discharge diagnoses between January 1, 1988, and May 31, 1990. The number of incidence cases of GBS observed within 30 days of gangliosides administration in a cohort of 13,373 treated subjects (0.0 cases) was not significantly different from that expected in the general population (0.014). Our study suggests that patients receiving gangliosides are not at increased risk of developing GBS. However, because of sample size limitations, these findings should be confirmed in a larger cohort study.

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

BackgroundEpidemiological 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.ObjectiveTo confirm the above assumption and to update MS frequency estimates in this area.Design and settingWe conducted a community-based intensive prevalence and incidence study, by adopting a complete enumeration approach.ResultsOn December 31, 2004, 423 patients (300 women and 123 men) suffering from definite or probable MS (Posers 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.ConclusionsThese 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.