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.

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.

Advanced laboratory techniques for diagnosing Toxoplasma gondii encephalitis in AIDS patients: significance of intrathecal production and comparison with PCR and ECL-western blotting.

The polymerase chain reaction (PCR) for detection of cerebral spinal fluid (CSF) Toxoplasma gondii DNA was combined with the study of intrathecal antibody synthesis by antibody specific index calculation (ASI) and the detection of specific oligoclonal IgG bands (OCB) by affinity mediated immunoblotting (AMI) in 11 AIDS patients with T. gondii encephalitis (TE) and in 20 control patients with or without neurological disorders. Enhanced chemiluminescence (ECL) western-blot technique was employed to evaluate the antigenic specificity of CSF-IgG towards individual T. gondii antigens. PCR was positive in all TE patients which displayed brain-derived or blood-derived specific OCB, even when comparative ASI failed. Four TE patients had a unique anti-T. gondii OCB restricted to the CSF and a strong antibody response toward the 29 kDa band by ECL western blot. This response could be an important marker to discriminate TE from other opportunistic central nervous system (CNS) infections in the course of AIDS.

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.

Oral aluminum and neuropsychological functioning. A study of dialysis patients receiving aluminum hydroxide gels.

Nine dialysis patients with significantly increased serum-aluminum levels due to chronic ingestion of aluminum hydroxide gels and eleven dialysis patients with normal serum-aluminum levels were tested neuropsychologically for generalized functions (intelligence, reasoning, memory) and for more specific abilities (visual memory, verbal and reading fluency, manual dexterity). All tests did not reveal any significant difference in neurophyscholigical functioning between the two groups. This finding seems to indicate that oral aluminum is not neurotoxic for man, even under circumstances of renal failure. This contradicts the idea that oral aluminum plays a role in etiology of dialysis dementia. However, the possibility cannot be excluded that aluminum overload in the present sample was not sufficient to induce changes in CNS functioning. Thus, until the importance of oral aluminum has been decided, it seems wise to keep all sorces of aluminum overload as low as possible.

Acute cerebrovascular insults in homozygous beta-thalassaemia: a case report.

Neurological complications following vascular thrombotic crises are frequent and occur in sickle cell anaemia and its variants, but are less well recognized in thalassaemias. A case of beta-thalassaemia major is reported complicated by an ischaemic lesion involving the right cerebellar hemisphere. The probable pathogenesis is considered and the literature on the matter briefly reviewed. In agreement with other reports, the interference of risk factors provided by or occurring in association with multiple blood-transfusions is hypothesized. Consequently, caution is recommended in giving large blood-transfusions to thalassaemic patients.

Clinical and audiological findings in a case of auditory agnosia.

A 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 the 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.

Epidemiological study of myasthenia gravis in the province of Ferrara, Italy.

The only prevalence rate of myasthenia gravis (MG) so far estimated in Italy by an epidemiological study carried out in Pavia, North Italy, indicates a prevalence quite similar to that observed in other countries. The purpose of the survey was to verify the frequency of the disease in a geographically well-defined and previously surveyed community. On the basis of 39 cases, on 31 December 1987 the prevalence per million was 105.3 (102.3 if standardized for the Italian population). This is the highest prevalence figure yet found, indicating a value similar to that established in Northern Europe. According to Kurtzke this high prevalence rate reflects the high standard of the local public health service, which permitted a more intensive search for affected subjects.

Predisposing factors in Bell's palsy: a case-control study.

The frequency of diabetes mellitus reported in subjects affected by Bell's palsy varies widely. In this investigation, a case-control study, we encountered a frequency of 24.8%. In addition, arterial hypertension and lipid disturbances were found to affect subjects with Bell's palsy more frequently than controls. These findings appear to suggest a primarily ischaemic pathogenesis for most cases of idiopathic peripheral facial paralysis. Furthermore, the finding of significantly lower taste impairment in diabetics than in non-diabetics with Bell's palsy may support the hypothesis of a vascular rather than a metabolic pathogenesis in these cases also. In fact, the vessels supplying the distal portion of the facial nerve, probably more affected in the diabetic patients in order to preserve taste sensation, have such a particular anatomical configuration that this might favour the onset of a diabetic small vessel disease which, in turn, would represent a factor of easier decompensation.

Systemic lupus erythematosus presenting with neurological disorders.

Six patients are described who developed a wide variety of neurological manifestations heralding systemic lupus erythematosus (SLE), which included epileptic seizures, stroke, peripheral polyradiculoneuropathy similar to Guillain-Barré syndrome, transverse myelopathy 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.

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.

T-cell phenotypic profiles in the cerebrospinal fluid and peripheral blood of multiple sclerosis patients.

Thirty-nine patients with clinically definite multiple sclerosis (MS) entered the study. Of 28 subjects with a relapsing-remitting course, 19 were classified in acute relapse, 9 in remission; 11 patients had a progressive course without remissions. Furthermore, 6 subjects with inflammatory neurological disease (IND), and 10 with non-inflammatory and non-neoplastic neurological disease (NIND) were investigated. We simultaneously studied cerebrospinal fluid (CSF) and peripheral blood (PB) T-, B- and NK-cell subsets, as defined by following monoclonal antibodies: anti-CD3, -CD4, -CD8, -CD19, -CD16, -HLA-DR and -IL-2-R. We found a significant increase of CD4+ T-cells compared with controls in CSF, with respect to PB, of MS patients, particularly in acute relapse. An increase of HLA-DR+ cell percentages in the CSF than in the PB in all MS groups, especially in attacks of MS but also in remission, was also observed, with a positive correlation between CD4+ T-cell and DR+ cell percentages both in the CSF as well as in the PB of relapsing MS patients. These findings, together with the increase of IL-2-R+ cells in the PB, particularly in relapsing MS, give further support for the presence of a systemic T-cell activation in MS.

[Assessment of biological risk of blood transmission among health workers at a Bari university hospital]. / Valutazione del rischio biologico a trasmissione ematica negli operatori di una Azienda Ospedaliera-Universitaria di Bari.

We have examined all occupational exposures to biological materials, occurred from September 2001 to December 2002, among health workers of Bari polyclinic. The reported exposures, through an appropriate questionnaire expressly predisposed, have been a total of 114. The nurses were the most exposed category (46.5%) followed by physicians (27.2%). The highest load of accidents happened in surgical area (53%) and at a greater extent after the first three hours of the work shift (60%). The instruments that have caused endermic lesions have been more frequently the hollow bone needles (53.2%). The serology for HBV, HCV, and HIV of source-patients was known in the 87.8% of cases: 13 patients were positive for HCV, 1 for HIV and 2 were HbsAg positive. All injured workers were submitted to serological screening for HBV, HCV, HIV; for nobody of them seroconversions were observed.

[The experience of the Operative Unit SETIL in Puglia]. / L'esperienza dell'Unità Operativa SETIL in Puglia.

(Epidemiological study on childhood tumors and leukaemia) study is an epidemiological case-control study, conducted in 15 Italian regions, including Apulia, to assess the possible risk of childhood cancer (leukaemia, LNH, and Neuroblastomes) resulting from exposures to electromagnetic fields (EMFs).

CSF levels of soluble HLA-G and Fas molecules are inversely associated to MRI evidence of disease activity in patients with relapsing-remitting multiple sclerosis.

Cerebrospinal fluid (CSF) concentrations of soluble human leukocyte antigen class I (HLA-I) (sHLA-I), HLA-G (sHLA-G) and anti-apoptotic Fas (sFas) molecules were measured by enzyme linked immunosorbent assay technique in 65 relapsing-remitting (RR) MS patients classified according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. Sixty-four patients with other inflammatory neurological disorders (OIND) and 64 subjects with noninflammatory neurological disorders (NIND) served as controls. CSF concentrations were higher in RRMS and in OIND than in NIND patients for sHLA-I (P < 0.02), greater in RRMS than in OIND and in NIND for sHLA-G (P < 0.001 and P < 0.01, respectively) and lower in RRMS than in OIND and in NIND for sFas (P < 0.001 and P < 0.02, respectively). An increase in CSF levels was identified in MRI active RRMS for sHLA-I (P < 0.01) and in MRI stable RRMS for sHLA-G (P < 0.01), whereas CSF values of sFas were decreased in RRMS without Gd-enhancing lesions (P < 0.02). In MS patients with no evidence of MRI disease activity, a trend towards an inverse correlation was found between CSF concentrations of sHLA-G and sHLA-I and between CSF levels of sHLA-G and sFas. Our results indicate that enhanced CSF levels of sHLA-I antigens most likely represent an indirect manifestation of intrathecal immune activation taking place in neuroinflammation. Conversely, reciprocal fluctuations in CSF sHLA-G and sFas levels observed when MRI disease activity resolved suggest that sHLA-G could play an immunomodulatory role in MS through Fas/FasL-mediated mechanisms.