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Biomedical subjects

G Orefice

Publications and source records attributed to G Orefice.

At least 19 recordsLinked to original sources

Treatment of multiple sclerosis with interferon beta in clinical practice: 2-year follow-up data from the South Italy Mobile MRI Project.

This follow-up study assessed the 2-year clinical and magnetic resonance imaging (MRI) outcomes of patients with multiple sclerosis (MS) originally enrolled in an MRI study conducted at eight centres in south Italy (the South Italy Mobile MRI Project). Of the 597 MS patients recruited at baseline, 391 returned for the follow-up study. Of these, 363 provided 2-year clinical and MRI follow-up data, and 215 were still undergoing treatment with one of four interferon beta regimens: Avonex, 30 mcg intramuscularly once weekly; Betaferon, 250 mcg subcutaneously (sc) every other day; Rebif 22 mcg sc three times weekly (tiw; Rebif 22); or Rebif 44 mcg sc tiw (Rebif 44). Over the 2-year follow-up period, patients receiving the higher dose of Rebif were more likely to remain free from relapses [odds ratio (OR) = 2.23] and from developing both new T2 (OR = 0.15) and new T1 black hole lesions (OR = 0.22), when compared with patients in the Avonex group. Despite some limitations in the trial design, the results from this follow-up study provide helpful clinical and MRI data on the efficacy of interferon beta regimens in MS patients treated in the clinical setting.

Analysis of Variance↗

Long-term clinical experience with weekly interferon beta-1a in relapsing multiple sclerosis.

Post-marketing surveillance studies are needed to assess the long-term safety, compliance and clinical efficacy of interferon beta-1a (IFNbeta-1a) therapy in multiple sclerosis (MS) patients. The goals of this study were to (i) assess the safety, compliance and clinical efficacy of long-term intramuscular (i.m.) IFNbeta-1a therapy in a large cohort of patients, and (ii) suggest possible predictors of therapeutic response. A total of 255 patients were included in the study. Mean time on therapy was 31.7 +/- 19.3 months. Within 3 years, 31% of patients discontinued treatment, mainly for disease activity. No significant sustained blood analysis alteration was observed over time, apart from a decrease of cholesterol levels. After 3 years of treatment, mean Expanded Disability Status Scale (EDSS) scores increased by 0.4 points compared with baseline. The mean annual relapse rate was reduced compared with baseline. Patients with < or = 2 relapses in the previous 2 years and with baseline EDSS scores of < or = 2 had a longer estimated time to first relapse and to progression and first relapse, respectively. These results confirm the safety and suggest a sustained effectiveness of i.m. IFNbeta-1a, extending the reported follow-up period to 6.3 years, and hypothesize the presence of possible predictors of clinical outcome.

Adjuvants, Immunologic↗

Grey matter loss in relapsing-remitting multiple sclerosis: a voxel-based morphometry study.

Global grey matter (GM) loss has been reported in multiple sclerosis (MS). We addressed the question of if and where GM loss is localized by means of optimized voxel-based morphometry, applied to MRI studies of 51 patients with clinically defined relapsing-remitting MS and 34 age-matched normal subjects, segmented into normal and abnormal brain tissues using a multiparametric approach. Segmented GM volumes were subsequently compared on a voxel-by-voxel basis to highlight regions of relative GM loss (P < 0.05, corrected for multiple comparisons at AnCova). Additionally, localized differences in brain asymmetry between the MS and the control groups were assessed by comparing on a voxel-by-voxel basis maps of GM differences between the two hemispheres (P < 0.05 corrected for multiple comparisons). In MS patients, GM volume was significantly decreased at the level of the left fronto-temporal cortex and precuneus, as well as of anterior cingulate gyrus and of caudate nuclei bilaterally. The only cortical region of significant GM loss in the right hemisphere was located in the postcentral area. Furthermore, GM loss regions were colocalized with increased GM asymmetries (Left < Right) in MS, confirming a preferential left-sided GM loss. Caudate atrophy correlated with lesion load, while no correlation between cortical regional GM loss and disease duration, clinical status or lesion load emerged. Our findings suggest that in RR-MS cortical GM reduction preferentially involves left fronto-temporal structures and deep GM, the latter correlating preferentially to global lesion load.

Adult↗

Brain atrophy and lesion load in a large population of patients with multiple sclerosis.

OBJECTIVE: To measure white matter (WM) and gray matter (GM) atrophy and lesion load in a large population of patients with multiple sclerosis (MS) using a fully automated, operator-independent, multiparametric segmentation method. METHODS: The study population consisted of 597 patients with MS and 104 control subjects. The MRI parameters were abnormal WM fraction (AWM-f), global WM-f (gWM-f), and GM fraction (GM-f). RESULTS: Significant differences between patients with MS and control subjects included higher AWM-f and reduced gWM-f and GM-f. MRI data showed significant differences between patients with relapsing-remitting and secondary progressive forms of MS. Significant correlations between MRI parameters and between MRI and clinical data were found. CONCLUSIONS: Patients with multiple sclerosis have significant atrophy of both white matter (WM) and gray matter (GM); secondary progressive patients have significantly more atrophy of both WM and GM than do relapsing-remitting patients and a significantly higher lesion load (abnormal WM fraction); lesion load is related to both WM and even more to GM atrophy; lesion load and WM and GM atrophy are significantly related to Expanded Disability Status Scale score and age at onset (suggesting that the younger the age at disease onset, the worse the lesion load and brain atrophy); and GM atrophy is the most significant MRI variable in determining the final disability.

Adolescent↗

Post-exercise facilitation and depression of motor evoked potentials to transcranial magnetic stimulation: a study in multiple sclerosis.

OBJECTIVE: To evaluate motor cortex excitability changes by transcranial magnetic stimulation (TMS) following repetitive muscle contractions in patients with multiple sclerosis (MS); to state whether a typical pattern of post-exercise motor evoked potentials (MEPs) is related to clinical fatigue in MS. METHODS: In 41 patients with definite MS (32 with fatigue and 9 without fatigue according to Fatigue Severity Scale) and 13 controls, MEPs were recorded at rest: at baseline condition, following repetitive contractions until fatigue, and after fatigue, to evaluate post-exercise MEP facilitation (PEF) and depression (PED). RESULTS: After exercise, MEP amplitude significantly increased both in patients and controls (PEF). When fatigue set in, MEP amplitude was significantly reduced in normal subjects (PED), but not in patients. Post-exercise MEP findings were similar both in patients with and without fatigue. CONCLUSIONS: Our findings suggest an intracortical motor dysfunction following a voluntary contraction in MS patients, possibly due to failure of depression of facilitatory cortical circuits, or alternatively of inhibitory mechanisms.

Adult↗

Epileptic seizures in multiple sclerosis: clinical and EEG correlations.

Epileptic seizures occur more frequently in multiple sclerosis (MS) patients than in the general population. We evaluated clinical, electroencephalographic (EEG) and magnetic resonance imaging (MRI) findings, as well as EEG-MRI correlations and the response to antiepileptic drugs (AEDs) in 270 consecutive patients with definite MS referred to our Department from 1995 to 2002. Thirteen (4.8%) subjects experienced epileptic seizures. In four cases, seizures manifested within 1-2 years ("early-onset"), and in six cases within 8-23 years ("late-onset") of MS diagnosis. Seizures were usually partial with secondary generalization. Thus, acute symptomatic seizures occurred in three cases. Epilepsy usually appeared late in the course of disease, although a single episode or a cluster of seizures can represent the onset symptom or a relapse of MS. Prognosis of epilepsy during the course of MS is usually good but the choice of AEDs remains a matter of debate.

Action Potentials↗

HELLP syndrome with reversible posterior leukoencephalopathy.

We report the case of a 30-year-old primipara who developed a triplet pregnancy after having received artificial insemination. At the end of the eighth month of pregnancy she had a generalized tonic-clonic seizure and at the same time blood chemistry was indicative of HELLP syndrome. Brain MRI and EEG were altered immediately after the episode but returned to normal during a 6-month follow-up period.

Adult↗

Aphasia as a rare presentation of monosymptomatic demyelinating disease: case report and review of the literature.

We present a case of sudden-onset aphasia due to a single pathological lesion, which at neuroradiological imaging studies was suggestive of glioma, while on biopsy proved be of demyelinating nature. Every cause of demyelinating lesions of the central nervous system was considered in the differential diagnosis, concluding for a primary demyelinating disease. The clinical and radiological differences between multiple sclerosis and acute disseminated encephalomyelitis are discussed. Although aphasia has already been described in demyelinating diseases, we underline its rarity as onset symptom.

Aphasia↗

Differential effects of three interferon betas on neutralising antibodies in patients with multiple sclerosis: a follow up study in an independent laboratory.

OBJECTIVE: To evaluate the incidence and the prevalence of neutralising antibodies (NABs) to three interferon beta (IFNbeta) products in patients with multiple sclerosis (MS). METHODS: Sera were tested from 125 patients with relapsing-remitting MS. Patients were treated with IFNbeta-1b (Betaferon, n = 29) 8 MIU subcutaneously every other day, IFNbeta-1a (Avonex, n = 44) 30 microg intramuscularly once weekly, or IFNbeta-1a (Rebif, n = 36) 22 microg subcutaneously three times weekly for 6 to 18 months. An additional 16 patients were treated with Rebif 22 microg intramuscularly once or twice weekly. NABs were assessed using the cytopathic effect assay before treatment and every three months during treatment. Patients with two or more consecutive positive samples were considered to be persistent NAB positive (NAB+). RESULTS: At baseline, no patients were NAB+. NABs developed during the first three months of treatment and continued to develop until month 18. Over 18 months of treatment, the risk of being persistent NAB+ was 31% for Betaferon, 15% for Rebif, and 2% for Avonex (Betaferon versus Avonex, p = 0.001; Betaferon versus Rebif, p = 0.19; Rebif versus Avonex, p = 0.04). In all patients with one or more NAB+ samples, the risk of becoming NAB+ was 38% for Betaferon, 18% for Rebif, and 7% for Avonex (Betaferon versus Avonex, p = 0.0007; Betaferon versus Rebif, p = 0.10; Rebif versus Avonex, p = 0.07). At month 18, the prevalence of persistent NAB+ patients was 31.6% for Betaferon, 18.7% for Rebif, and 4% for Avonex. Numbers of NAB+ patients observed were similar with intramuscular Rebif and with subcutaneous Rebif. CONCLUSION: The three IFNbeta preparations have different degrees of immunogenicity, with Betaferon producing the highest incidence of NABs and Avonex the lowest. These differences should be considered by neurologists when selecting treatment for their patients with MS because NABs can reduce both bioavailability and clinical efficacy of IFNbeta.

Adult↗

Carotid atherosclerosis and ischemic stroke in young patients.

BACKGROUND: Epidemiological studies indicate a high prevalence of carotid atherosclerosis in elderly patients with ischemic stroke. The aim of this study was to investigate the presence of early carotid atherosclerotic lesions in young subjects with ischemic stroke, in the absence of the common atherosclerotic risk factors. METHODS: We studied 98 young patients with first ischemic stroke (54 males and 44 females; mean age 41.2 years; range 32-50) and 96 healthy controls. All subjects underwent ultrasonographic scanning of the carotid arteries according to a standardized protocol. RESULTS: The carotid intima-media thickness was significantly increased in the patient group (p<0.001) compared with controls. In addition, the prevalence of carotid atherosclerotic plaques was greater in the patients than in the controls (p<0.001). In particular, we detected 18 non-occlusive carotid plaques and 16 thrombotic occlusions. In 8 patients, the lesions were bilateral. The echographic pattern of the plaques was hard in 8 cases, soft in 5 cases, and mixed in the remaining 5 cases. CONCLUSIONS: We detected an increased wall thickness of the carotid arteries and an increased prevalence of carotid atherosclerotic lesions and carotid thrombotic occlusions in young patients with ischemic stroke, with a relative low incidence of cardiovascular risk factors. This finding suggests that arterial intima-media thickness per se is an important determinant of vascular disease in young patients. The data also provide indirect support for the potential role of genetic factors in the genesis of atherosclerosis in young patients.

Adult↗

HLA-DRB1*1501 and response to copolymer-1 therapy in relapsing-remitting multiple sclerosis.

BACKGROUND: Copolymer 1 (Cop-1) is a random synthetic amino acid copolymer, effective in the treatment of the relapsing-remitting form of MS (RRMS). In vitro and in vivo studies suggest that the mechanism of Cop-1 involves its binding to major histocompatibility complex class II molecules as an initial step. OBJECTIVE: To assess a possible relationship between human leukocyte antigen (HLA) alleles and response to Cop-1 therapy. METHODS: Eighty-three patients with RRMS, 44 treated with Cop-1 and 39 with interferon beta-1a (IFNbeta-1a) for 2 years, were typed by molecular methods for HLA class II genes and subgrouped according to clinical outcome. RESULTS: Data have shown a possible positive correlation between presence of DRB1*1501 and response to Cop-1 therapy (p = 0.008). No relationship between HLA alleles and therapy has been found in IFNbeta-1a treated patients. CONCLUSIONS: Results suggest that DRB1*1501 might be relevant for the clinical outcome in Cop-1 treated patients and, if confirmed in larger studies, it could be helpful in the selection of RRMS patients for different therapeutic options.

Adult↗

Effect of diabetes on some primitive reflexes.

Primitive reflexes (PRs) are present in newborns; they disappear as the brain matures and increase in frequency in healthy elderly individuals. Primitive reflexes are more frequent in some neurological disorders than in age-matched controls. The aim of this study was to investigate the effect of diabetes on some PRs. We examined three PRs (glabellar tap, snout and palmomental reflexes) in 376 subjects: 111 normal age-matched controls, 60 patients with cerebrovascular disease (CVD) and 205 patients with type 2 diabetes mellitus. The latter patients were divided into three groups: (1) diabetics without neurological complications (D); (2) diabetics with cerebrovascular disease (D-CVD); and (3) diabetics with polyneuropathy (D-PN). The frequency of PRs was increased in CVD, unchanged in D-CVD (except palmomental) and greatly reduced in D and D-PN. It is possible that the vascular lesions in perforating arteries of the pons in diabetic subjects, previously studied in some pathological reports, can account for the reduced occurrence of primitive reflex responses.

Aged↗

Benign intracranial hypertension: a non-thrombotic complication of the primary antiphospholipid syndrome?

Benign intracranial hypertension is a rare complication of systemic lupus erythematosus often attributed to cerebral sinus thrombosis which impairs venous drainage and cerebrospinal fluid outflow. We report the case of a woman with a primary antiphospholipid syndrome who developed benign intracranial hypertension with no actual evidence of venous cerebral thrombosis and with no other possible cause for this clinical manifestation than high titres of anticardiolipin antibodies and a lupus anticoagulant.

Adult↗