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Biomedical subjects

M R Tola

Publications and source records attributed to M R Tola.

At least 19 recordsLinked to original sources
PubMed2006

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.

Adult↗
PubMed2004

Explosive-aggressive behavior related to bilateral subthalamic stimulation.

We describe a patient with Parkinson's Disease who underwent bilateral subthalamic nucleus deep brain stimulation and later presented with episodes of aggressive behavior disorder with disturbed impulse control and an inability to control anger likely related to the deep brain stimulation "switch-on stimulation". We hypothesize that increasing voltage intensity could influence neighboring passing fibers coming from basal limbic system that are involved in the regulation of affect and emotional behavior. We suggest investigating these neuropsychological disturbances considering their influence on quality of life after surgery.

Aggression↗
PubMed2004

Human herpesvirus 6 infects the central nervous system of multiple sclerosis patients in the early stages of the disease.

The presence and the replicative state of human herpesvirus 6 (HHV-6) were evaluated in clinical samples from multiple sclerosis (MS) patients at the first time of MS diagnosis. HHV-6 variant B was present in peripheral blood mononuclear cells of 5/32 (15%) patients, but persisted with a latent infection. Viral sequences were present also in cerebrospinal fluid (CSF), both free in the liquid (7/32, 22%) and latent in the cellular fraction (3/32, 9%), as shown by analysis of viral transcription. In these cases, variant A was detected. HHV-6 DNA sequences present in the CSF were associated to mature viral particles. In fact, in vitro infectious assays of CSF showed the presence of replication-competent virions. These results show that about 20% of MS patients have active foci of HHV-6 variant A infection in the early stages of the disease and suggest that viral replication takes place within the central nervous system.

Central Nervous System Diseases↗
PubMed2003

Neurophysiological study of corticomotor pathways in restless legs syndrome.

OBJECTIVE: To test the variations in cerebral motor excitability in patients with primary restless legs syndrome (RLS) by using electrophysiological techniques. In RLS patients periodic legs movements (PLMs) in sleep and wake have been described and it is hypothesised that PLMs result from a sleep-related disinhibition of descending central motor inhibitory pathways. Moreover, in primary RLS, these modifications are still debated. METHODS: In 15 patients with primary RLS, transcranial magnetic stimulation (TMS) was carried out using several paradigms, particularly paired pulse TMS with short interstimulus intervals (ISI) in abductor digiti minimi (ADM) and tibialis anterior (TA) muscles. RESULTS: Short ISI paired TMS showed a significant decrease in inhibition and increase in facilitation in ADM muscles. This result was even more evident in TA muscles of patients as compared to the controls and these modifications were more evident in the limbs which were more affected by PLM. Moreover, intracortical (corticocortical) inhibition (ICI) and intracortical facilitation (ICF) unchanged their biphasic time course. CONCLUSIONS: In our study the changes in short paired-pulse ICI and ICF revealed the presence of an altered excitability of central motor pathways, with good correlation with asymmetric distribution of symptoms.

Adult↗
PubMed2001

Multiple sclerosis: infectious hypothesis.

In the search for the etiology of multiple sclerosis (MS), consideration has been given in turn to infectious agents, to genetic markers, and more recently to a combination of genetic and environmental factors, but after over a century of research, a definite conclusion has not been reached. The hypothesis that an infectious agent is responsible for triggering MS is perhaps one of neurology's most enduring notions. Interest in an infectious etiology has waxed and waned over the last two centuries since Pierre Marie first proposed that MS often starts as an infectious process. The possible role of infectious agents has been suggested by: the different geographic gradients in frequency among Caucasians; changes in prevalence due to migration, and the effect of age at migration; the suggestion of epidemics and clusters of cases in some small communities; and the remarkably low degree of concordance in monozygotic twins. The infectious hypothesis is strongly supported by the different temporal patterns of the disease in different geographic areas. Incidence rates have remained stable in some areas, but have changed over time in other regions. On the other hand, the hypothesis is hampered by the lack of evidence for a specific agent, and the weakness of the results of analytical studies that have tested the association between MS and previous infections. Despite these drawbacks, recent studies of a few select pathogens suggest that viral or bacterial infections or reactivations may trigger clinical exacerbations in relapsing-remitting MS.

Adult↗
PubMed2000

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.

Adolescent↗
PubMed2000

Novel human herpesviruses and multiple sclerosis.

It has been suggested that human herpesvirus 6 (HHV-6) might be involved in the pathogenesis of multiple sclerosis (MS). However, studies of the association between HHV-6 and MS are hindered by the difficulty in discriminating between latent and active infection. We undertook a study to determine whether HHV-6 establish a systemic active infection in the course of MS, and to investigate possible roles of HHV-7, a herpesvirus closely related to HHV-6. To discriminate between latent and active infection, we analysed viral transcription. The results indicate that both viruses are prevalent in PBMCs of MS patients as in healthy controls, and that viral sequences are maintained in a non-transcriptional state. These observations indicate that further studies should define the state of viral persistence in the central nervous system.

DNA, Viral↗
PubMed1999

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.

Adolescent↗
PubMed1999

Neurological involvement in primary Sjögren's syndrome: clinical and instrumental evaluation in a cohort of Italian patients.

To evaluate nervous system involvement in a cohort of Italian patients with primary Sjögren's syndrome (pSS), 87 unselected patients (83 female, and four male) observed consecutively at our institution over a period of 5 years were screened by clinical and instrumental (MRI, SPECT, electrophysiological testing, CSF analysis) investigations for peripheral and central neurological abnormalities. Seroimmunological parameters and extraglandular features other than neurological manifestations were also evaluated. Seven patients had central nervous system (CNS) disease (8%), mostly non-focal dysfunction, and 12 had peripheral nervous system (PNS) disease (13.8%), mostly mild or severe sensory or sensory-motor polyneuropathies. One patient had concomitant CNS and PNS involvement. Compared with CNS disease, PNS involvement occurred in older patients (> 50 years), independent of the disease duration. Patients with and without neurological abnormalities did not differ for seroimmunological parameters (including antiphospholipid antibodies) or extraglandular manifestations. From a statistical point of view, the only relevant finding was the detection of a slight increase in serum IgA and IgM levels (p < 0.05) in patients with an intact nervous system. Neurological involvement in pSS, be it central or peripheral, is not a rare finding. A careful clinical neurological evaluation, combined with a multiplicity of instrumental investigations, is recommended in the global assessment of pSS patients.

Adult↗
PubMed1999

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.

Adolescent↗
PubMed1999

Human herpesvirus 6 is latent in peripheral blood of patients with relapsing-remitting multiple sclerosis.

Studies of the association between HHV-6 and multiple sclerosis are hindered by the difficulty in discriminating between latent and active infection. A follow up study was undertaken of patients with multiple sclerosis, searching peripheral blood mononuclear cells for molecular markers associated with HHV-6 latency and lytic replication. The results show that HHV-6 is latent and did not support systemic infection in patients with multiple sclerosis. Likewise, patients with multiple sclerosis did not show any evidence of active infection with other human herpesviruses HHV-7 and HHV-8.

Adolescent↗
PubMed1999

Temporal trend and factors associated with delayed hospital admission of stroke patients.

The effectiveness of stroke treatment depends on the time interval between onset of symptoms and admission to hospital. The purpose of our investigation was to assess, over a 10-year period, the mean delay in admission to hospital in stroke patients to determine factors which might be associated with this delay, to define the putative number of patients available for accrual in clinical trials, and to identify strategies aimed at decreasing the time to admission. We collected data on all stroke patients consecutively admitted to our clinic from 1986 to 1995. The following variables were investigated: age, sex, educational and occupational level, home accommodation, family and personal history of vascular disease or factors known to affect the risk of vascular disease, and type and severity of stroke. The individual and independent contribution of these variables was assessed by univariate and multivariate analysis. The accurate time of stroke onset was established for 760 patients. Of these, 24.7% were admitted within 1 h from the onset of symptoms, 41% within 2 h, 54% within 4 h and 72.5% within 12 h. The mean delay was 21 +/- 2 h (SE) and the median was 3.5 h. Acute onset of neurological deficits, stroke severity and family history of cerebrovascular disease were associated with earlier presentation. According to the current guidelines for thrombolytic therapy, only 16% of the patients could have been included in a clinical trial. This study suggests that despite a relatively short time to hospital admission in most patients and an altered help-seeking behavior over time, many stroke patients did not present early enough to be recruited for clinical trials or to benefit from new treatments. The majority of patients with timely presentation were not eligible for acute treatment, or were subjects with severe stroke for whom caution is advised before initiating thrombolytic therapy. It has been suggested that the patient's indecision to seek medical help is the most important reason for a delayed hospital admission of stroke patients. These results underscore the importance of interventions aimed at reducing the delay in stroke treatment induced by patients who are unaware of the decisive role of the time of treatment induction. The finding that earliest admissions for stroke comprised patients with a previous history of cerebrovascular disease suggests that an education campaign might highlight the importance of an early admission.

Adult↗
PubMed1998

Cerebral hypoperfusion detected by SPET in early neuro-Behçet syndrome.

We used brain single-photon emission tomography (SPET) to detect hypoperfused areas in 15 consecutive Behçet syndrome patients. Five were suspected of having neuro-Behçet syndrome, having at least one neurological symptom. For these patients, SPET was performed within 1 month of the onset of nervous system involvement. The 15 patients fulfilled the criteria of the International Study Group for Behçet syndrome. Neurological assessment and SPET were complemented by EEG in all five patients with suspected neuro-Behçet syndrome and by magnetic resonance imaging in three. Brain SPET detected hypoperfused regions in all five neurological patients; EEG showed abnormalities in three. Magnetic resonance imaging was normal in the three patients in whom it was performed. SPET was negative in all patients without neurological involvement and 20 healthy controls. SPET detected a reduction in brain blood flow in early neuro-Behçet syndrome, but there was no definitive correlation between the hypoperfused brain regions and the clinical features. Further studies are required to evaluate the significance of brain hypoperfusion and the value of SPET in the early diagnosis of neuro-Behçet syndrome.

Adult↗
PubMed1998

An epidemiological study of multiple sclerosis in central Sardinia, Italy.

OBJECTIVES: To verify morbidity estimates in central Sardinia, Italy. METHODS: A prevalence study was performed in the province of Nuoro, Central Sardinia, which has a population of 273,768 inhabitants (135,383 men and 138,385 women). A complete enumeration approach was adopted by using all possible case-collection sources. RESULTS: On prevalence day, December 31, 1993, 394 subjects (124 men and 270 women) living in the study area were known to suffer from definite and probable MS, giving a crude prevalence rate of 143.9 cases per 100,000 people, 91.6 for males and 195.11 for females. The crude prevalence estimated on December 31, 1985, based on 282 MS cases alive in the study area, was 102.94 per 100,000. CONCLUSION: This study reinforced central Sardinia's position as a high and rising prevalence area for MS.

Adolescent↗
PubMed1997

Exogenous gangliosides and Guillain-Barré syndrome. An observational study in the local health district of Ferrara, Italy.

A retrospective study was carried out in the Ferrara Local Health District, Italy, for the period 1981-1993 (average resident population: 177,235 inhabitants) to establish whether people exposed to exogenous gangliosides had a higher risk of Guillain-Barré syndrome. The incidence of Guillain-Barré syndrome of 1.9/100,000 population/year [95% confidence interval (CI): 1.3-2.5] reported in Ferrara Local Health District in the same period was used as a reference for comparison. The data bank of Ferrara Local Health District made it possible, first to estimate the number of individuals exposed to gangliosides in the resident population of Ferrara Local Health District (3.7%), the number of ganglioside prescriptions and the number of cases of Guillain-Barré syndrome who had treatment with gangliosides (nine patients, 20.9%), and, secondly, to verify the sequence of events between the ganglioside injection and the onset of the disease. Seven of the nine patients (77.8%) received gangliosides as treatment for peripheral neuropathy (Guillain-Barré syndrome onset before gangliosides were prescribed). For the other two patients (22.2%) a possible appropriate temporal sequence between ganglioside injection and onset of Guillain-Barré syndrome was found. Based on two possible ganglioside-related cases, the risk of Guillain-Barré syndrome was higher in the exposed (0.53/100,000 population/month following ganglioside injection; 95% CI: 0.06-1.91) compared with the unexposed population, but the difference was not significant. When only individuals prescribed with mixed gangliosides were considered (both possible ganglioside-related Guillain-Barré syndrome cases received mixed gangliosides), the risk of Guillain-Barré syndrome was higher (0.64/100,000 population/month following ganglioside injection; 95% CI: 0.08-2.31) but the difference from the risk in unexposed individuals was not statistically significant. The relative risk for the exposure to mixed gangliosides was borderline (relative risk = 4.3; 95% CI: 1.0-17.8). The wide 95% confidence intervals were a consequence of sample size limitations. Considering also that the exposed and unexposed groups differed in age (those exposed were older than those unexposed and the age-specific incidence of Guillain-Barré syndrome in the study population increased with increasing age), the present findings question either a strong increased risk of Guillain-Barré syndrome in people exposed to exogenous gangliosides or an immunogenic role of these agents in humans. However, because of the limited sample size, the results are not conclusive.

Adolescent↗
PubMed1997

Prognosis of childhood epilepsy: a community-based study in Copparo, Italy.

We performed a community-based study among children and adolescents with idiopathic and cryptogenic epilepsy and onset of the seizures between 0 and 19 years of age on the prognosis of being seizure-free. The study population was recruited during a descriptive investigation in the Local Health Service of Copparo (USL 34), Ferrara, Northern Italy. We included 111 patients (61 males and 50 females). The average length of follow-up was 18.8 years (ranging from 7 to 24 years). The cumulative probability of being in remission was 81.2% at 15 years after onset and the estimated percentage of patients in remission without therapy was 56% for the same time period. At 15 years after the onset of epilepsy, approximately 20% of patients continued to have seizures; nearly 25% continued to take antiepileptic drugs but had been free of seizures for at least 5 years; nearly 56% had been without seizures and free of medication for at least 5 years. Seizure type, gender, age at onset of the illness, epileptic abnormalities on EEG, family history of convulsive disorders, number and frequency of seizures prior to the start of treatment were found not to be helpful as prognostic factors. This community study, carried out on patients without the well known factors that adversely affect prognosis, confirms that the prospect of seizure control and for withdrawal of therapy is (generally) good.

Adolescent↗
PubMed1997

Phenytoin-induced gingival overgrowth: a community-based cross-sectional study in Ferrara, Italy.

A community-based cross-sectional study was carried out in Ferrara, Northern Italy, to verify the frequency of gingival overgrowth in chronic phenytoin (PHT) users and the risk factors associated with its development. All subjects taking phenytoin were identified using the computerized list of drug prescriptions available in the study area. Most of the subjects were interviewed and underwent an oral examination to evaluate their periodontal condition. The prevalence of gingival enlargement in chronic PHT users was about 40%. In our study, sex, age age at onset of therapy, treatment duration, and oral hygiene were not significantly associated with the risk of developing gingival overgrowth. A direct relationship with daily dose was found to be an independent risk factor. Younger age and poorer oral hygiene seemed to predispose to the severest level of gingival involvement. These results support data from experimental studies by suggesting that drug-induced gingival overgrowth is a dose-dependent side effect whose severity could be affected by local factors.

Adolescent↗