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Giuseppe Orefice

Publications and source records attributed to Giuseppe Orefice.

5 recordsLinked to original sources

Levetiracetam for cerebellar tremor in multiple sclerosis: an open-label pilot tolerability and efficacy study.

PURPOSE: Disabling tremor is frequent in multiple sclerosis (MS) and its treatment remains challenging. We conducted an open-label trial to evaluate the effect of levetiracetam (LEV) to treat cerebellar tremor in MS patients. PATIENTS AND METHODS: Fourteen MS patients, aged 27 to 57 years, with cerebellar tremor. Tremor duration ranged from 3 to 14 years. The tremor clinical rating scale, the spiral drawings scale, and ataxia clinical scale were used to assess the severity of tremor. Data about the tremor-induced disability were obtained by using the specific Activities of Daily Living Questionnaire (ADL). LEV was orally administered at a starting dose of 500 mg twice daily for one week followed by increments of 500 mg twice daily each week up to the target dose of 50 mg/Kg/day. Patients were evaluated at baseline and two weeks after the end of titration phase. The Wilcoxon matched-pairs test was used for statistical analysis. RESULTS: Eleven patients completed the trial. LEV administration was associated with subjective and objective improvement of the tremor, with significant lowering of all tremor measurements' sum of scores as well as of ADL mean score between the baseline and follow-up. No correlation was found between the degree of improvement of the tremor and the disease duration or progression. LEV was well tolerated by subjects who completed the study. CONCLUSIONS: LEV could be useful for the management of cerebellar tremor in MS and the good tolerability makes it easy to test. LEV long-term efficacy should be confirmed in extended studies.

Activities of Daily Living↗

Neuropsychological assessment, quantitative MRI and ApoE gene polymorphisms in a series of MS patients treated with IFN beta-1b.

Few trials issued the effect of disease-modifying medications on cognitive functions in multiple sclerosis. We designed an open-label longitudinal study to evaluate, during 2 years, cognitive performance and its relationship with MRI data and ApoE polymorphism findings in a group of relapsing-remitting (RR) multiple sclerosis (MS) Interferon (IFN) beta-1b-treated patients (median age 30 years, median disease duration 3.4 years). Complete neuropsychological battery was grouped into attention, information learning/memory, language and visuo-spatial functions. Fifty-two patients (33 females) were enrolled in the study. Six patients (11.5%) dropped out, mainly due to side effects. At baseline neuropsychological evaluation, we found 54% normal, 42% mildly impaired and 4% moderately impaired patients. At 2 years follow-up, cognitive status was stable in 65%, improved in 33% and worsened in 2% of patients. No significant relations were found between global cognitive outcome vs. EDSS change, clinical disease activity, MRI data or ApoE gene polymorphisms over the 2 years follow-up. EDSS and MRI fractional volumes were found to correlate with the performance at single tests. Twenty-one patients (45.6%) showed active MRI scans throughout the study, without any worsening at the corresponding neuropsychological examination. This ongoing trial suggests a possible beneficial effect of IFN beta-1b treatment on cognitive functions in RRMS patients. Extension of follow-up and further data analyses are needed to confirm and clarify these findings.

Adolescent↗

Absence of cerebrospinal fluid oligoclonal bands is associated with delayed disability progression in relapsing-remitting MS patients treated with interferon-beta.

To assess the role of CSF oligoclonal bands (OB) in determining the clinical outcome in patients with relapsing-remitting multiple sclerosis (RRMS) treated with IFN-beta, we carried out a retrospective, multicentre, observational study recruiting 209 RRMS patients from six MS centres from northern, central and southern areas of Italy under treatment with IFN-beta-1a i.m., IFN-beta-1a s.c. and IFN-beta-1b s.c. Twenty-two of 209 patients (10.6%) showed no OB in CSF. The patients without had, at disease onset, significantly higher frequency of visual disturbances (p=0.02) and less sensory involvement (p=0.04) than those with OB. A statistical trend (p=0.056) towards a longer time to reach sustained disability progression during treatment was found in patients without compared to those with OB. Thirty-six of 187 (19%) patients with OB worsened by at least 1 EDSS point compared to none of 22 (0%) OB-negative patients (p=0.017). The delaying of disability progression in OB-negative patients during treatment was significantly dependent only on the number of baseline MRI T2-weighted lesions (p=0.012) that was found to be significantly lower in OB-negative than in OB-positive patients (p=0.04). The absence of OB and low number of baseline T2-weighted lesions in this cohort of MS patients are favourable prognostic factors influencing the clinical response to IFN-beta treatment in RRMS patients.

Adult↗

Brain tissue volume changes in relapsing-remitting multiple sclerosis: correlation with lesion load.

The aim of this study was to simultaneously measure in vivo volumes of gray matter (GM), normal white matter (WM), abnormal white matter (aWM), and cerebro-spinal fluid (CSF), and to assess their relationship in 50 patients with relapsing-remitting multiple sclerosis (RR-MS) (age range, 21-59; mean EDSS, 2.5; mean disease duration, 9.9 years), using an unsupervised multiparametric segmentation procedure applied to brain MR studies. Tissue volumes were normalized to total intracranial volume providing corresponding fractional volumes (fGM, faWM, fWM, and fCSF), subsequently corrected for aWM-related segmentation inaccuracies and adjusted to mean patients' age according to age-related changes measured in 54 normal volunteers (NV) (age range 16-70). In MS patients aWM was 23.8 +/- 29.8 ml (range 0.4-138.8). A significant decrease in fGM was present in MS patients as compared to NV (49.5 +/- 3.2% vs 53.3 +/- 2.1%; P < 0.0001), with a corresponding increase in fCSF (13.0 +/- 3.8% vs 9.1 +/- 2.4%; P < 0.0001). No difference could be detected between the two groups for fWM (37.5 +/- 2.6% vs 37.6 +/- 2.2%). faWM correlated inversely with fGM (R = -0.434, P < 0.001 at regression analysis), and directly with fCSF (R = 0.473, P < 0.001), but not with fWM. There was a significant correlation between disease duration and EDSS, while no relationship was found between EDSS or disease duration and fractional volumes. Brain atrophy in RR-MS is mainly related to GM loss, which correlates with faWM. Both measures do not appear to significantly affect EDSS, which correlates to disease duration.

Adult↗

Hyperhomocysteinemia and other inherited prothrombotic conditions in young adults with a history of ischemic stroke.

BACKGROUND AND PURPOSE: The mechanisms of ischemic stroke in young adults are poorly understood. During the last years, several studies suggested a role for genetic factors predisposing to thrombophilia and for moderate hyperhomocysteinemia in this setting. METHODS: We evaluated in 132 consecutive patients (66 males, 66 females; mean+/-SD age, 38.4+/-11.7 years; mean+/-SD age at first event, 34.8+/-10.9 years; range, 6 months to 50 years) referred to our center between January 1997 and December 1999 for a history of young adult ischemic stroke (age at first event, <51 years) the prevalence of factor V (FV) Leiden, prothrombin (FII) G20210A, and C677T and 5,10-methylenetetrahydrofolate reductase (MTHFR) gene mutations and fasting serum total homocysteine levels. Two hundred sixty-two apparently healthy subjects (117 males, 145 females; mean+/-SD age, 36+/-13.2 years) served as controls. RESULTS: Total homocysteine levels differed significantly (P=0.004, t test) between patients and controls: 13.03+/-18.61 versus 10.75+/-6.24 micromol/L (mean+/-SD), respectively. In contrast, homozygosity for the TT mutation of the MTHFR gene was 30 of 132 (22.7%) in patients and 45 of 262 (17.2%) in controls; this difference was not statistically significant (P>0.05, chi(2) test). However, when we stratified the whole population according to genotype, fasting serum homocysteine levels were significantly higher in TT patients than in TT controls (25.3+/-36.8 versus 15+/-11.6 micromol/L; P=0.02, t test). Mutations of FV Leiden and of FII G20210A gene are currently reported to be associated with a tendency toward ischemic stroke. Their frequencies were not statistically significantly different between patients and controls in this setting: 7 of 132 (5.3%) versus 17 of 262 (6.5%) for FV Leiden and 10 of 132 (7.6%) versus 16 of 262 (6.1%) for FII G20210A, respectively (all P>0.05, chi(2) test). CONCLUSIONS: In the present cohort of patients, moderate hyperhomocysteinemia is the only variable that helps to identify young adults with a history of ischemic stroke.

Adult↗