Ezio Paolino

A Descriptive Study of Epilepsy in the District of Copparo, Italy, 1964–1978

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

Motor neuron disease in the province of Ferrara, Italy, in 1964–1982

We carried out an intensive incidence, prevalence, and mortality survey of motor neuron disease (MND) in the province of Ferrara, northern Italy. Based on 72 patients, the mean incidence per year for the period 1964 through 1982 was 0.98 cases per 100,000. On December 31, 1981, the prevalence rate was 3.95 per 100,000. In the 19-year period the average mortality rate was 0.83 per 100,000 per year. The disease was more common in men, in individuals aged 50 to 70 years, and in residents in rural areas engaged in agricultural work. A retrospective case-control study, confirming a significantly higher frequency of MND in farmers and persons living in rural areas, revealed that the disease was more common in the lower social classes to which most unskilled and heavy laborers belong. In addition, a significantly increased risk for MND was found in patients with previous histories of trauma, but confounding variables may account for this association.

Cerebrospinal fluid and serum levels and intrathecal production of active matrix metalloproteinase-9 (MMP-9) as markers of disease activity in patients with multiple sclerosis.

In this study, we employed a sensitive activity assay system to measure cerebrospinal fluid (CSF) and serum levels of active matrix metalloproteinase-9 (MMP-9) in 37 relapsing-remitting (RR), 15 secondary progressive (SP) and nine primary progressive (PP) multiple sclerosis (MS) patients, grouped according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. We also studied, as neurological controls, 48 patients with other inflammatory neurological disorders (OIND) and 48 with non-inflammatory neurological disorders (NIND). To assess active MMP-9/TIMP-1 circuit, CSF and serum levels of MMP-9 tissue inhibitor TIMP-1 were quantified by ELISA in the same patient population. CSF mean levels of active MMP-9, CSF active MMP-9/TIMP-1 ratios and intrathecal active MMP-9 synthesis, as indicated by specific index, were more elevated in MS than in NIND (P <0.05, <0.02 and <0.02, respectively), serum active MMP-9/TIMP-1 ratio was higher in MS (P<0.01) and OIND (P<0.02) than in NIND, and serum TIMP-1 concentrations were lower in MS than in NIND (P<0.05). More importantly, serum active MMP-9 mean levels, serum active MMP-9/TIMP-1 ratio and intrathecal production of active MMP-9 were increased in MS patients with clinical (P<0.001, <0.001 and <0.05, respectively) and MRI (P<0.001, <0.001 and <0.02, respectively) disease activity, whereas CSF mean concentrations of active MMP-9 and CSF active MMP-9/TIMP-1 ratio were enhanced only in MS patients with MRI evidence of disease activity (P<0.02 and <0.01, respectively). Altogether, these findings suggest that a shift in MMP-9/TIMP-1 balance towards proteolytic activity of MMP-9 could be relevant in MS immune dysregulation. In addition, our results indicate that CSF and serum levels of active MMP-9 may represent a potential surrogate biomarker for monitoring MS disease activity. In particular, serum active MMP-9/TIMP-1 ratio seems to be a very appropriate indicator of ongoing MS inflammation, since it is easily measurable.

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.

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.

Systemic lupus erythematosus presenting with neurological disorders

SummarySix patients are described who developed a wide variety of neurological manifestations heralding systemic lupus erythematosus (SLE), which included epileptic seizures, stroke, peripheral polyradiculoneuro pathy similar to Guillain-Barré syndrome, transverse my elopathy and multifocal disorders with remitting course mimicking multiple sclerosis. The peculiarity of these cases was that the neurological disorders remained the only manifestations of SLE for many years and the nervous system appeared to be the main target even after the development of systemic SLE. In five patients the prognosis was favourable and corticosteroid treatment led to prolonged remission.

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.

Clinical and audiological findings in a case of auditory agnosia

SummaryA case is reported of severe agnosia for verbal and non-verbal sounds without associated aphasic disorder. A CT scan revealed bilateral, temporal lobe lesions from two ischaemic accidents that had occurred 9 months apart. The search for subtle deficits in this patient showed normal sensitivity to changes in the intensity and frequency of simple sounds; in contrast, his ability to discriminate sound duration and musical note sequences was severely impaired. The simultaneous recording of the whole auditory-evoked response pattern revealed no abnormality in the early components, which reflect the activation of the auditory nuclei and pathways of the brain stem. However, the middle and late components were delayed and slowed. These results and others in the literature suggest that the neocortex in man, as in other mammals, plays an essential role in the temporal aspects of hearing. Also, the two main ingredients commonly recognized in auditory agnosia, i.e. word deafness and the inability to interpret non-verbal sounds, are caused by the disruption of elementary, bilaterally represented cortical functions which start the processing of every kind of auditory information.

Intrathecal synthesis of soluble HLA-G and HLA-I molecules are reciprocally associated to clinical and MRI activity in patients with multiple sclerosis

The aim of this study was to provide further insight into the effective contribution of classical soluble HLA-A, B and C class Ia (sHLA-I) and non-classical soluble HLA-G class Ib (sHLA-G) molecules in immune dysregulation occurring in multiple sclerosis (MS). We evaluated by enzyme-linked immunosorbent assay (ELISA) technique intrathecal synthesis and cerebrospinal fluid (CSF) and serum levels of sHLA-I and sHLA-G in 69 relapsing-remitting (RR), 21 secondary progressive (SP) and 13 primary progressive (PP) MS patients stratified according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. We also tested, as neurological controls, 91 patients with other inflammatory neurological disorders (OIND) and 92 with non-inflammatory neurological disorders (NIND). Eighty-two healthy volunteers served as further controls for sHLA-I and sHLA-G determinations. An intrathecal production of sHLA-I and sHLA-G detected by specific indexes was significantly more frequent in MS patients than in controls (p<0.01). An intrathecal synthesis of sHLA-I was prevalent in clinically (p<0.02) and MRI active (p<0.001) MS, whereas a CSF-restricted release of sHLA-G predominated in clinically (p<0.01) and MRI stable (p<0.001) MS. sHLA-I levels were low in the serum of clinically active (p<0.001) and high in the CSF of MRI active (p<0.01) MS. Conversely, sHLA-G concentrations were decreased in the serum of clinically stable MS (p<0.01) and increased in the CSF of MRI inactive MS (p<0.001). The trends towards a negative correlation observed between CSF and serum concentrations and intrathecal synthesis of sHLA-I and sHLA-G in patients without evidence of clinical and MRI activity confirmed that intrathecal production and fluctuations in CSF and serum concentrations of sHLA-I and sHLA-G were reciprocal in MS. Our results suggest that, in MS, a balance between classical sHLA-I and non-classical sHLA-G products modulating both MRI and clinical disease activity in opposite directions may exist.