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Biomedical subjects

M Zaffaroni

Publications and source records attributed to M Zaffaroni.

At least 37 records · Page 2Linked to original sources

Differential diagnosis of acute myelopathies.

Diagnosis of acute myelopathy applies to subjects with acute motor involvement, segmental sensory loss and sphincter dysfunction, reaching a maximum no later than 4 weeks after onset. Among the different causes of acute myelopathy (e.g. compressive, vascular, traumatic or toxic lesions, paraneoplastic involvement and electrical injury), acute myelitis due to infective agents or to an autoimmune-inflammatory process frequently causes problems relating to the differential diagnosis of multiple sclerosis (MS) and its potential risk of developing MS.

Acute Disease↗

Cranial nerve, brainstem and cerebellar syndromes in the differential diagnosis of multiple sclerosis.

A clinically isolated syndrome indicating a pathological process involving the cranial nerves or the posterior fossa may constitute a hard diagnostic challenge for the clinician. Whereas internuclear ophthalmoplegia, for example, is almost pathognomonic of multiple sclerosis (MS), other clinical presentations are often puzzling. The main alternative causes of symptoms that may suggest a clinical onset of MS are reviewed here, grouped in principal clinical syndromes, with particular attention to some rare, recently recognised conditions.

Brain Stem↗

Neurological manifestations of gastrointestinal disorders, with particular reference to the differential diagnosis of multiple sclerosis.

Neurological manifestations of gastrointestinal disorders are described, with particular reference to those resembling multiple sclerosis (MS) on clinical or MRI grounds. Patients with celiac disease can present cerebellar ataxia, progressive myoclonic ataxia, myelopathy, or cerebral, brainstem and peripheral nerve involvement. Antigliadin antibodies can be found in subjects with neurological dysfunction of unknown cause, particularly in sporadic cerebellar ataxia ("gluten ataxia"). Patients with Whipple's disease can develop mental and psychiatric changes, supranuclear gaze palsy, upper motoneuron signs, hypothalamic dysfunction, cranial nerve abnormalities, seizures, ataxia, myorhythmia and sensory deficits. Neurological manifestations can complicate inflammatory bowel disease (e.g. ulcerative colitis and Crohn's disease) due to vascular or vasculitic mechanisms. Cases with both Crohn's disease and MS or cerebral vasculitis are described. Epilepsy, chronic inflammatory polyneuropathy, muscle involvement and myasthenia gravis are also reported. The central nervous system can be affected in patients with hepatitis C virus (HCV) infection because of vasculitis associated with HCV-related cryoglobulinemia. Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is a disease caused by multiple deletions of mitochondrial DNA. It is characterized by peripheral neuropathy, ophthalmoplegia, deafness, leukoencephalopathy, and gastrointestinal symptoms due to visceral neuropathy. Neurological manifestations can be the consequence of vitamin B1, nicotinamide, vitamin B12, vitamin D, or vitamin E deficiency and from nutritional deficiency states following gastric surgery.

Celiac Disease↗

Transmigration of PBMNCs from beta-IFN-1b-treated MS patients: a one-year longitudinal study.

To evaluate the effects of in vivo beta-IFN-1b treatment on transmigration of mononuclear cells, we monitored for one year in vitro mononuclear cells trafficking through HUVECs monolayers stratified over a collagen gel during beta-IFN-1b treatment of 7 RR MS patients. The number of transmigrated cells was analysed before treatment (T0) and after 3 (T3), 6 (T6) and 12 months (T12); at the same time, levels of serum MMP-9 were quantified. The number of transmigrated cells decreased during treatment compared to pre-treatment values: the lowest number of transmigrated cells was detected at T3, and, although transmigration was still lower at T12, there was a trend to a return to pre-treatment levels over time. The amount of MMP-9 also decreased during therapy, although we could not find an absolute correlation between transmigration and levels of MMP-9, nor between either parameter and the clinical course of patients.

Adult↗

Thyroid function and autoimmunity during interferon beta-1b treatment: a multicenter prospective study.

Thyroid dysfunction and autoimmunity have been reported during type I interferon therapy, namely interferon-alpha for chronic hepatitis or interferon-beta for multiple sclerosis. To define the frequency of thyroid dysfunction and autoimmunity during interferon-beta treatment, 156 multiple sclerosis patients were prospectively followed up by 18 centers for 1 yr after starting interferon-beta-1b treatment. Serial clinical assessments and tests of thyroid and liver function and antithyroid autoantibodies (all performed by the same centralized laboratory) were conducted every 3 months. TSH and antithyroid autoantibodies against human TG or thyroid microsomal antigens were measured by immunoradiometric methods; free T3 and T4 were measured by chromatographic assays. Longitudinal occurrence of thyroid or liver alterations or of autoantibodies was analyzed with the generalized estimating equations method, correcting for the correlation of repeated measurements of the same subject over time. Pretreatment comparison with a control group of 437 healthy blood donors did not show significant differences in the frequency of thyroid dysfunction or antithyroid autoantibody positivity. During interferon-beta treatment, the de novo frequency of thyroid alteration was 8.3%, that of liver alteration was 37.5%, and that of antithyroid autoantibody was 4.5%. Generalized estimating equations analysis demonstrated that the frequency of liver alteration significantly increased during treatment compared with the baseline value (odds ratio, 7.03; confidence interval, 2.49-19.9), whereas that of thyroid alteration or of antithyroid autoantibodies did not. The frequency of thyroid dysfunction during interferon-beta treatment showed random, nonsignificant changes over time and, in addition, was not correlated to antithyroid autoantibody positivity.

Adolescent↗

Infants of immigrant parents in Italy. A national multicentre case control study.

BACKGROUND: The aim of this study was to evaluate health state of newborns of immigrated parents from developing countries. METHODS: Hospital records of 69,605 infants born during 1996/1997 in Italy were reviewed comparing, in a case-control study, each infant of immigrated parents to two infants born immediately before and after to Italian parents. RESULTS: Of the 69,605 newborns 3906 (5.6%) were born to immigrated parents. This prevalence prolongs the increasing trend observed during the last 10 years of infants born to immigrated parents and reduces the fall of the birth rate linked to the few infants born to Italian parents. It was influenced by geographical factors, being higher in Northern-Central Italy (7%) than in Southern and Insular Italy (2.8%), as consequence of more elevated incomes in these Italian regions. The origin countries of immigrated parents were mainly Northern Africa (31.7%), Eastern Europe (18%) and Sub Saharan Africa (11.6%). Infants of immigrated parents showed higher incidences of prematurity, low birth weight, asphyxia and neonatal mortality rate than newborns with Italian parents. These higher incidences appeared related to some risk factors such as higher parity, short gestational age, some maternal infections, maternal drug dependence, maternal age less than 18 years, low familiar income, inadequate obstetric cares, difficulty to accessing the public health services. CONCLUSIONS: The health problems of infants with immigrated parents are mainly related to social disadvantage and can be overcome improving the social state, the lifestyles and the obstetric cares of the immigrated women, so as monitoring their risk pregnancies.

Adolescent↗

The prognostic value of age, gender, pregnancy and endocrine factors in multiple sclerosis.

The evolution of multiple sclerosis at the time of diagnosis remains unpredictable since a reliable prognostic marker is not yet available. Nevertheless, a series of useful prognostic indicators have been singled out from epidemiological studies. Young age at onset, female gender, relapsing/remitting course, and sensitive or visual disturbances as initial symptoms are considered favourable prognostic factors. Conversely, late age at onset, male gender, progressive course, and pyramidal or cerebellar symptoms at the first episode predict an unfavourable evolution. Another prognostic indicator has been recognized in pregnancy: although the overall effect of pregnancy on short-term MS course is neutral, in the long-term it seems to protect from disease progression. Most prognostic indicators seem to act through the neuro-endocrine-immune network, modulating the immune response in the context of the Th1/Th2 paradigm.

Adult↗

The prognosis of idiopathic optic neuritis.

We evaluated the risk of developing clinically definite multiple sclerosis (CDMS) after acute isolated optic neuritis in 102 patients in a follow-up study (duration 6.5 +/- 2.0 years). The probability of CDMS was 13% after 2 years, 30% after 4 years, 38% after 6 years, and 49% after 8 and 10 years. CDMS occurred in 42 (59%) of 71 patients with brain lesions detected with magnetic resonance imaging (MRI). No patient with normal MRI exam developed the disease. Patients with 3 or more MRI-detected lesions presented a shorter first interattack interval and a higher relapse rate compared to subjects with only 1 or 2 lesions. The predictive value of CSF examination and of evoked potentials was poor.

Adult↗

Relevance of interleukin 1 receptor antagonist intron 2 polymorphism in Italian MS patients.

The A1/A1 genotype of the anti-inflammatory cytokine interleukin 1 receptor antagonist (IL-1Ra) polymorphism was more frequent in 339 Italian MS patients than in healthy controls (HCs) (odds ratio = 1.83). A more aggressive disease course was also associated with A1+ genotypes and might reflect the reduced ability of mononuclear cell cultures of A1+ HCs to produce IL-1Ra. We conclude that an IL-1Ra gene polymorphism is associated with occurrence of disease and clinical course variability in Italian MS patients.

Adult↗

Long-term follow-up of isolated optic neuritis: the risk of developing multiple sclerosis, its outcome, and the prognostic role of paraclinical tests.

We evaluated the risk of developing clinically definite multiple sclerosis (CDMS) after an acute attack of isolated optic neuritis (ON) in 112 patients, in relation to demographic and paraclinical findings. Patients were examined by brain MRI, CSF analysis, and multiple evoked potentials (EPs); 10 were lost to follow-up, and the other 102 were enrolled in a prospective study (follow-up duration 6. 3 +/- 2.2 years). Of these, 37 (36.3%) developed CDMS after a mean interval of 2.3 +/- 1.6 years. The risk of developing CDMS was 13% after 2 years, 30% after 4, 37% after 6, and 42% after 8 and 10 years. Gender, age, and season of ON onset did not affect the risk. MS occurred in 37 of 71 patients (52.1%) with one MRI lesion or more; no patient with a normal MRI developed the disease. MS developed more frequently in patients with intrathecal IgG synthesis than in those without (43% vs. 28%), but the difference was not statistically significant. Multiple EPs showed a slight predictive value only including somatosensory EPs of the lower limb. Multiple sclerosis was mild in most cases (EDSS 2.2 +/- 1.9). The EDSS was less than 4 in 32 cases (86%), between 4 and 6 in 2 (5%), higher than 6.5 in 3 (8%).

Adult↗

Adhesion of mononuclear cells from multiple sclerosis patients to cerebral vessels in cryostat sections of normal human brain.

Leukocyte extravasation across the blood-brain barrier is a critical event in the pathogenesis of multiple sclerosis (MS). This complex multistep process includes the adhesion of leukocytes to the endothelial cells of the central nervous system microvasculature. To investigate this phenomenon in MS, we developed a modified version of the frozen-section assay. Peripheral blood mononuclear cells (PBM) from 26 MS patients, 26 healthy controls and 10 patients with other inflammatory non- neurological diseases (OIND) were co-incubated with cryostat sections of normal brain white matter, immunohistochemically labelled with anti-CD45 antibody and counterstained with Giemsa stain. CD45-positive PBM adherent to transected microvasculature were counted with an automated image analyzer. MS patients showed an increased number of vessel-bound PBM (48.8 +/- 36.4) with respect to healthy controls (27.4 +/- 20.7, P = 0.01) and OIND patients (22.6 +/- 7.8, P = 0.01). Significant differences were also obtained counting the number of vessel-bound PBM as a percent of total vascular cells between MS patients (12.7 +/- 7.2%) and healthy controls (6.9 +/- 5.4%, P = 0.002) or OIND patients (7.4 +/- 4.4%, P = 0.03). We confirm that PBM from MS patients show an increased potential of binding to cerebral vessels. The frozen-section assay provides a unique tool to study in situ the molecular interactions of leukocytes with brain vascular structures.

Adult↗

Modulation of ICAM-1, VCAM-1 and HLA-DR by cytokines and steroids on HUVECs and human brain endothelial cells.

The in vitro effects of dexamethasone (Dx) and low and high-dose 6-methylprednisolone (MP) on the expression of adhesion molecules ICAM-1,VCAM-1 and class II antigen HLA-DR on human brain endothelial cells (HBECs) was studied. HBECs were obtained from the surgical specimen of a multiple sclerosis patient undergoing brain surgery for vascular aneurysm. HBECs obtained from apparently normal brain capillaries of surgical specimens of two patients undergoing brain surgery for a meningioma and a low-grade glioma, respectively, were used as controls. The effect of steroids was studied both in the basal condition and after stimulation with proinflammatory cytokines (gamma-IFN and TNF-alpha). In order to detect possible endothelium local tissue specific differences, the experiment was repeated using human umbilical vein endothelial cells (HUVECs). Only high-dose MP was able to down-regulate TNF-alpha-induced VCAM-1 expression on endothelial cells.

Adult↗

Occurrence and clinical relevance of an interleukin-4 gene polymorphism in patients with multiple sclerosis.

An epistatic gene interaction has been advocated to explain disease susceptibility in multiple sclerosis (MS). Cytokine genes are possible candidates due to the central role played by cytokines in the regulation of the immune-mediated pathogenetic process leading to central nervous system demyelination in these patients. Since interleukin (IL)-4 gene polymorphisms have been associated with immune-mediated diseases, we have analysed the relationship between a variable number of tandem repeat polymorphism of the IL-4 gene and clinical and physiological features of 256 sporadic MS patients and 146 healthy controls. Genotype frequencies were similar between the MS group and healthy controls. However, in MS patients a positive and significant correlation (r = 0.91; p < 0.001) was found between the carriage rate of the IL-4 B1 allele (from 0.21 to 0.36) and age of disease onset. No association was found between IL-4 alleles and disease progression, sex or ethnic background of the patients. Our results show that the IL-4 B1 allele is associated with late onset of MS and therefore might represent a modifier of age of onset rather than a susceptibility factor for patients with MS.

Adult↗

Multiple sclerosis in childhood: clinical features of 149 cases.

From the retrospective study of 3375 patients affected by clinically definite or probable multiple sclerosis (MS), 149 patients were collected with onset of the disease before the age of 16 years (4.4%). Female/male ratio was higher than that of the adult onset MS (AOMS) population (2.2 vs 1.6) particularly at ages of onset after 12 years (3.0, P = 0.007 vs AOMS). Among initial symptoms, those suggesting brainstem dysfunction (25%) were more frequent compared to other systems and compared to AOMs symptoms; motor and sensory disturbances were slightly less frequent (respectively 17.5% and 18.3%). Optic neuritis appeared in 16.5% of cases with onset in childhood and in 16.2% of cases with AOMS, cerebellar disturbances respectively in 9.1% and 7.7%. The first interattack-interval and the clinical course of early onset MS did not differ significantly from AOMS. In early onset MS patients with disease duration < 8 years, cases with EDSS > 6 were slightly more frequent than in the AOMS group (P = 0.04). The frequency of cases for different levels of disability was similar for disease duration > 8 years.

Adolescent↗

Cerebral involvement in celiac disease: a serial MRI study in a patient with brainstem and cerebellar symptoms.

A patient with celiac disease and relapsing-progressive symptoms suggesting brainstem and cerebellar involvement underwent serial MRIs. The first examination revealed multiple enhancing and nonenhancing lesions. Thereafter, a large enhancing cerebellar lesion appeared, followed by severe cerebellar atrophy. The presence of structural neuronal damage was confirmed by proton MR spectroscopy and magnetization transfer imaging. MRI results and CSF findings suggested that neurologic complications were more likely due to an inflammatory process.

Adult↗

Isolated optic neuritis and its prognosis for multiple sclerosis: a clinical and paraclinical study with evoked potentials. CSF examination and brain MRI.

Our study evaluated the frequency of developing multiple sclerosis (MS) after acute isolated optic neuritis (ON), the possible association with risk factors (gender, age), and the diagnostic and prognosis role of paraclinical tests. We studied 100 ON patients (mean age 28.9 years: SD 8.9): 85 patients were regularly followed up. Sixty-six patients underwent multimodality evoked potential (EP) test, examination and brain MRI within six months of the onset of ON. Over a mean follow-up of 5.2 years, MS occurred in 28/85 cases. The risk of developing MS after four years was 0.35 at life-table analysis, regardless of gender or age at the onset of ON. Visual EPs in unaffected eyes were abnormal in 25.4%, brainstem auditory EPs in 6.5% somatosensory EPs in 8.1%, upper limb motor EPs in 6.8% of the tested patients; intrathecal IgG synthesis was revealed in 51.7% and MRI lesions in 73.8%. Fifty-one of the patients who underwent paraclinical tests were followed up for more than one year, and MS occurred in 13 cases. All of these presented MRI lesions, nine intrathecal IgG synthesis, and two abnormal extraocular EPs. The risk of developing MS after four years was 0.33 in patients with MRI lesions; the simultaneous presence of intrathecal IgG synthesis increased the risk to 0.46.

Adult↗