Giuseppe Orefice

Flunarizine in Prophylaxis of Childhood Migraine: A Double-Blind, Placebo-Controlled, Crossover Study

An 8-month, double-blind, placebo-controlled, crossover trial of flunarizine in the prophylaxis of migraine has been performed in 70 children. After 4 weeks of medication-free base-line observation, 35 children (group A) received flunarizine (5 mg/day) and 35 (group B) received placebo over a 12-week period. After a 4-week washout they crossed treatments for another 12 weeks. Sixty-three patients completed the trial. In both groups flunarizine significantly reduced the frequency and average duration of headache attacks. In group A efficacy was maintained after placebo crossover for the last 4 months of the study. Five subjects in group B stopped placebo because of ineffectiveness; two children in group A discontinued flunarizine treatment, one because of excessive daytime sedation and the other because therapy was ineffective. The main side effects were daytime sedation and weight gain. It is concluded that flunarizine is an effective drug for the treatment of childhood migraine. In a study of this length no serious side effects were discovered.

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.

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.

Correlation between fatigue and brain atrophy and lesion load in multiple sclerosis patients independent of disability.

BACKGROUND Fatigue is a major problem in multiple sclerosis (MS), and its association with MRI features is debated. OBJECTIVE To study the correlation between fatigue and lesion load, white matter (WM), and grey matter (GM), in MS patients independent of disability. METHODS We studied 222 relapsing remitting MS patients with low disability (scores <or=2 at the Kurtzke Expanded Disability Status Scale). Lesion load, WM and GM were measured by fully automated, operator-independent, multi-parametric segmentation method. T1 and T2 lesion volume were also measured by a semi-automated method. Fatigue was assessed by the Fatigue Severity Scale (FSS), and patients divided in high-fatigue (FSS>or=5; n=197) and low-fatigue groups (FSS<or=4; n=25). RESULTS High-fatigue patients showed significantly higher abnormal white matter fraction (AWM-f), T1 and T2 lesion loads, and significant lower WM-f, and GM-f. Multivariate analysis showed that high FSS was significantly associated with lower WM-f, and GM-f. Females and highly educated patients were significantly less fatigued. CONCLUSION These results suggest that among MS patients with low disability those with high-fatigue show higher WM and GM atrophy and higher lesion load, and that female sex and higher levels of education may play a protective role towards fatigue. Furthermore, they suggest that in MS, independent of disability, WM and GM atrophy is a risk factor to have fatigue.

The heterogeneity of early Parkinson's disease: a cluster analysis on newly diagnosed untreated patients.

Background The variability in the clinical phenotype of Parkinson’s disease seems to suggest the existence of several subtypes of the disease. To test this hypothesis we performed a cluster analysis using data assessing both motor and non-motor symptoms in a large cohort of newly diagnosed untreated PD patients. Methods We collected data on demographic, motor, and the whole complex of non-motor symptoms from 100 consecutive newly diagnosed untreated outpatients. Statistical cluster analysis allowed the identification of different subgroups, which have been subsequently explored. Results The data driven approach identified four distinct groups of patients, we have labeled: 1) Benign Pure Motor; 2) Benign mixed Motor-Non-Motor; 3) Non-Motor Dominant; and 4) Motor Dominant. Conclusion Our results confirmed the existence of different subgroups of early PD patients. Cluster analysis revealed the presence of distinct subtypes of patients profiled according to the relevance of both motor and non-motor symptoms. Identification of such subtypes may have important implications for generating pathogenetic hypotheses and therapeutic strategies.

Atorvastatin combined to interferon to verify the efficacy (ACTIVE) in relapsing-remitting active multiple sclerosis patients: A longitudinal controlled trial of combination therapy

A large body of evidence suggests that, besides their cholesterol-lowering effect, statins exert anti-inflammatory action. Consequently, statins may have therapeutic potential in immune-mediated disorders such as multiple sclerosis. Our objectives were to determine safety, tolerability and efficacy of low-dose atorvastatin plus high-dose interferon beta-1a in multiple sclerosis patients responding poorly to interferon beta-1a alone. Relapsing—remitting multiple sclerosis patients, aged 18—50 years, with contrast-enhanced lesions or relapses while on therapy with interferon beta-1a 44 µg (three times weekly) for 12 months, were randomized to combination therapy (interferon + atorvastatin 20 mg per day; group A) or interferon alone (group B) for 24 months. Patients underwent blood analysis and clinical assessment with the Expanded Disability Status Scale every 3 months, and brain gadolinium-enhanced magnetic resonance imaging at screening, and 12 and 24 months thereafter. Primary outcome measure was contrast-enhanced lesion number. Secondary outcome measures were number of relapses, EDSS variation and safety laboratory data. Forty-five patients were randomized to group A (n = 21) or B (n = 24). At 24 months, group A had significantly fewer contrast-enhanced lesions versus baseline (p = 0.007) and significantly fewer relapses versus the two pre-randomization years (p < 0.001). At survival analysis, the risk for a 1-point EDSS increase was slightly higher in group B than in group A (p = 0.053). Low-dose atorvastatin may be beneficial, as add-on therapy, in poor responders to high-dose interferon beta-1a alone.

Gender differences in non-motor symptoms in early, drug naïve Parkinson’s disease

Gender differences in brain structure and function may lead to differences in the clinical expression of neurological diseases, including Parkinson’s disease (PD). Few studies reported gender-related differences in the burden of non-motor symptoms (NMS) in treated PD patients, but this matter has not been previously explored in drug-naïve PD patients. This study is to assess gender differences in the prevalence of NMS in a large sample of early, drug-naïve PD patients compared with age and sex-matched healthy controls. Two hundred early, drug-naïve PD patients and ninety-three age and sex-matched healthy controls were included in the study. Frequency of NMS was evaluated by means of the Non-Motor Symptoms Questionnaire. The difference in gender distribution of NMS was evaluated with the χ2 exact test; multiple comparisons were corrected with the Benjamini–Hochberg method. Male PD patients complained of problems having sex and taste/smelling difficulties significantly more frequently than female PD patients. Furthermore, men with PD complained more frequently of dribbling, sadness/blues, loss of interest, anxiety, acting during dreams, and taste/smelling difficulties as compared to healthy control men, while female PD patients reported more frequently loss of interest and anxiety as compared with healthy control women. This study shows specific sex-related patterns of NMS in drug-naïve PD. In contrast with previous data, female PD patients did not present higher prevalence of mood symptoms as compared to male PD patients. Comparison with healthy controls showed that some NMS classically present in premotor and early stage of disease (i.e., acting out during dreams, taste/smelling difficulties) are more frequent in male than in female patients.

Epileptic seizures in multiple sclerosis: clinical and EEG correlations.

Abstract.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.

Multiple sclerosis and headache co-morbidity. A case-control study

The prevalence of primary headache (PH) in a multiple sclerosis (MS) sample vs. control healthy subjects was investigated at a neurological clinic in 2004–2005: 122 of 238 (51%) MS patients and 57 of 238 (23%) controls proved to be affected by headache. The groups did not differ for the rates of PH types. Headache types of MS patients were comparable to those of PH patients that were observed at the same institute in a case-control comparison. First symptoms of headache preceded those of MS in two thirds of cases. Headache features did not significantly change after MS onset. Comorbidity of MS and PH could be explained by some common clinical and biological traits.

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

PurposeDisabling 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 methodsFourteen 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.ResultsEleven 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.ConclusionsLEV 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.