Long-term outcome in multiple sclerosis patients treated with fingolimod.

BACKGROUND AND PURPOSE: Ongoing disease activity during treatment has been associated to worse disability outcomes in patients with Multiple Sclerosis (MS). The aim of this study was to assess the 5-year response to fingolimod (FTY) treatment in patients with relapsing-remitting (RRMS) in a real-life setting. METHODS: We included RRMS patients who received FTY for at least 6 months and had a follow-up ≥ 60 months. Treatment response was assessed through the No Evidence of Disease Activity (NEDA)-3 status. RESULTS: Eighty-eight patients were included, of which 51 (58.0%) were NTZ-naïve and 37 (42.0%) NTZ-switchers. The mean age was 38.9 (9.5) years and 58 (65.9%) were females. The proportion of patients on FTY treatment who maintained the NEDA-3 status at 5 years was 55.9% among NTZ-naïve patients and 35.0% among NTZ-switchers (p=0.138). Predictors of NEDA-3 status were lower Expanded Disability Status Scale score at baseline (adjOR=0.28, 95% CI 0.10-0.77; p=0.013) in NTZ-naïve patients and fewer relapses in the 12 months before starting FTY in NTZ-switchers (adjOR=0.05, 95% CI 0.003-0.79; p=0.034). CONCLUSIONS: This study supports the potential of FTY as a disease-modifying treatment for the long-term management of RRMS patients. Patients with milder disability and fewer clinical relapses before treatment may achieve a better disease control.

Cerebral hemodynamics in patients with multiple sclerosis.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system. Although the currently predominant view is that of an autoimmune inflammatory condition, changes in brain vasculature can occur and contribute to pathophysiology. The aim of this study was to evaluate cerebral hemodynamics in patients with MS and explore its relationship with disease status. METHODS: Patients with MS and age- and sex- matched healthy controls were recruited. All participants underwent assessment of cerebral hemodynamics through transcranial Doppler ultrasonography. Cerebral vasomotor reactivity (CVR) to hypercapnia was measured by the breath-holding index (BHI). RESULTS: A total of 80 patients with MS and 80 healthy controls were recruited. BHI values obtained in healthy controls, relapsing-remitting (RR)-MS and secondary progressive (SP)-MS patients were 1.15±0.11, 0.87±0.18 and 0.51±0.20, respectively (p<0.001). Group-wise, patients showed decreased CVR in comparison to controls and BHI values were significantly lower in SP-MS than in RR-MS patients. At linear regression analysis, the disease form was significantly associated with cerebral hemodynamics being the SP phenotype an independent predictor of lower BHI values [ß=-0.36, 95% confidence interval (CI): -0.44 to -0.27, p<0.001; adjusted ß=-0.37, 95% CI: -0.50 to -0.23, p<0.001). CONCLUSIONS: Cerebrovascular hemodynamic insufficiency in MS may be secondary to the downstream effects of neuro-inflammatory cascades.

Persistence to oral disease-modifying therapies in multiple sclerosis patients.

Dimethyl fumarate (DMF), fingolimod (FTY) and teriflunomide (TFN) are oral disease-modifying therapies (DMTs) approved for relapsing-remitting multiple sclerosis (RRMS) whose efficacy and tolerability have been separately assessed in phase III trials. Conversely, little evidence exists about their head-to-head comparison. The aim of the study was to evaluate the 1-year persistence to DMF, FTY and TFN in patients with RRMS. Patients affected by RRMS who started treatment with DMF, FTY or TFN were identified. The study end-point was 12-month drug persistence as time to discontinuation and proportion of patients who discontinued medication within 1-year. A total of 307 patients were included (DMF = 114, FTY = 129, TFN = 64). The mean times to discontinuation were 144 (84), 189 (72) and 138 (120) days in the DMF, FTY and TFN cohorts (p = 0.036). At 12-month, the proportion of patients discontinuing medication was lower for subjects taking FTY (9.8%) compared with those starting DMF (21.9%) and TFN (23.6%) (p = 0.020). Compared to FTY cohort, DMF [adjOR = 3.26 (1.38-7.70); p = 0.007] and TFN [adjOR = 2.89 (1.10-7.63); p = 0.032] treated patients were more likely to have discontinued their drug at 1-year since initiation. In patients with RRMS, FTY was associated with a better persistence profile as compared to DMF and TFN.

Efficacy of topiramate and valproate in chronic migraine.

OBJECTIVES: The aim of this study was to compare the efficacy of sodium valproate and topiramate in treating chronic migraine. METHODS: Forty-nine patients with chronic migraine were randomly assigned to 1 of 2 groups of treatment: 750 mg/day valproate or 75 mg/day topiramate. Efficacy variables were number of days with headache over a 30-day period and changes in Migraine Disability Assessment (MIDAS) scores at 3 months. RESULTS: At baseline the 2 groups had similar numbers of days with headache and mean MIDAS scores. At the end of the treatment period, a significant reduction in 30-day headache frequency with respect to baseline (P < 0.00001) and a significant reduction in MIDAS scores (P < 0.00001) were recorded in both groups. There were no significant differences in beneficial effects between the 2 drugs. DISCUSSION: Valproate and topiramate seem to be able to manage successfully chronic migraine without substantial differences in efficacy and tolerability. This affords clear practical advantages-in the event of failure of or intolerance for one treatment, the patient may be switched to the other.

Prediction of disability progression in fingolimod-treated patients.

PURPOSE: The aim of the study was to evaluate whether early disease activity during fingolimod treatment could predict disease progression in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: We included RRMS patients who received fingolimod for at least 12 months with a ≥36 months of follow-up. Early disease activity was assessed by the modified Rio score (MRS). Association between MRS at 12 months and time to disability progression over the following two years was assessed using Kaplan-Meier survival curves analysis and Cox proportional hazards model. RESULTS: At 1 year from starting treatment, 14 (58.3%), 5 (20.8%), 3 (12.5%) and 2 (8.3%) subjects had a MRS=0, 1, 2, and 3, respectively. The risk of disability progression in the next 2 years was associated to the MRS and increased from 21.1% in patients with MRS=0-1 to 80% in those with MRS≥2 (adjusted HR=19.67; 95% CI=2.30-167.79; p=0.006). CONCLUSIONS: Early disease activity is suggested to be associated with the risk of disease progression in patients receiving fingolimod and MRS could be a reliable tool to identify the subjects at higher risk of unfavorable course.

Prognostic significance of personality profiles in patients with chronic migraine.

BACKGROUND AND OBJECTIVE: The aim of this study was to assess whether the psychological profile may have prognostic significance in chronic migraine patients. METHODS: The Minnesota Multiphasic Personality Inventory-2 was used for the psychological assessment of patients with chronic migraine to explore personality traits. Patients with psychiatric disease and medication overuse were excluded. One hundred and two patients completed the study. Migraine-related disability was measured using the Migraine Disability Assessment questionnaire at baseline (T(0)) and again after 2 years (T(1)), during which patients received prophylactic treatment for migraine. At T(1) patients were classified into those exhibiting significant improvement (group 1: scores reduced by at least 50%) and those with unsatisfactory changes in headache-related disability (group 2: scores reduced by less than 50%). RESULTS: At T(1) 49 patients were in group 1 and 53 in group 2; at T(0), group 1 patients had significantly lower Minnesota Multiphasic Personality Inventory-2 scores in the neurotic (hypochondriasis: P < .01; depression: P < .001; hysteria: P < .01) and schizophrenia (P < .05) scales. None of the other variables studied, ie, age, sex, age at migraine onset, number of years from chronic migraine onset, T(0) Migraine Disability Assessment score, T(0) headache frequency, severity and temporal pattern (continuous vs intermittent) differed significantly between the groups. CONCLUSIONS: Findings suggest that psychological factors can influence the clinical course of chronic migraine and that psychological evaluation with Minnesota Multiphasic Personality Inventory-2 may be a reliable approach to obtain prognostic data and information for therapy planning in patients with chronic migraine.

Reactive oxygen species plasmatic levels in ischemic stroke.

Oxidative stress is probably one of the mechanisms involved in neuronal damage induced by ischemia-reperfusion, and the antioxidant activity of plasma may be an important factor providing protection from neurological damage caused by stroke-associated oxidative stress. The aim of this study was to investigate the status of oxidative stress, NO and ONOO(-) levels in patients with atherothrombotic and lacunar acute ischemic stroke and iNOS, eNOS and nitrotyrosine expression in the same patients. Plasma ONOO(-) levels were significantly higher in patients than in controls while NO decreases in patients in respect to controls. Densitometric analysis of bands indicated that iNOS and N-Tyr protein levels were significantly higher in patients in respect to controls. This study has highlighted a significant NO decrease in our patients compared with controls and this is most probably due to the increased expression of inducible NO synthase by the effect of thrombotic attack. In fact, the constitutive NO isoforms, which produce small amounts of NO, are beneficial, while activation of the inducible isoform of NO, which produces much more NO, causes injury, being its toxicity greatly enhanced by generation of peroxynitrite. The significant ONOO(-) increase observed in our patients, compared to controls, is most probably due to reaction of NO with O(2)(*-) . These findings suggest that free radical production and oxidative stress in ischemic stroke might have a major role in the pathogenesis of ischemic brain injury. Peroxynitrite might be the main marker of brain damage and neurological impairment in acute ischemic stroke.