Half-dose fingolimod for treating relapsing-remitting multiple sclerosis: Observational study.

OBJECTIVES: To investigate the efficacy and safety of fingolimod (FTY) 0.5 mg administered every other day (FTY-EOD) compared to every day (FTY-ED) in multiple sclerosis patients. METHODS: Multicentre retrospective observational study. Clinical, laboratory and neuroimaging data were consecutively collected from 60 FTY-EOD and 63 FTY-ED patients. Baseline characteristics were compared using logistic regression. Efficacy in preventing occurrence of relapses and demyelinating lesions was tested using propensity score-adjusted Cox and linear regressions. RESULTS: Weight was inversely associated with risk of switch to FTY-EOD because of any reason (odds ratio (OR) = 0.94, 95% confidence interval (95% CI) = 0.89-0.99, p = 0.026), and female sex and lower baseline lymphocyte count were positively associated with switch because of lymphopenia. Compared to FTY-ED patients, FTY-EOD patients were at higher risk of developing relapses (hazard ratio (HR) = 2.98, 95% CI = 1.07-8.27, p = 0.036) and either relapses or new magnetic resonance imaging (MRI) demyelinating lesions (combined outcome, HR = 2.07, 95% CI = 1.06-4.08, p = 0.034). Within FTY-EOD, treatment with natalizumab before FTY and lower age were positively associated with risk of developing relapses and combined outcome, respectively (HR = 25.71, 95% CI = 3.03-217.57, p = 0.002 and HR = 0.85, 95% CI = 0.77-0.96, p = 0.005). FTY-EOD was overall well tolerated. CONCLUSION: Disease reactivation was observed in a significant proportion of patients treated with FTY-EOD. Neurologists should be cautious when reducing FTY administration to every other day, especially in younger patients and those previously treated with natalizumab.

Posterior tibial nerve stimulation in the management of lower urinary tract symptoms in patients with multiple sclerosis.

INTRODUCTION AND HYPOTHESIS: Bladder dysfunction is a frequent symptom complex in patients with multiple sclerosis (MS) and often compromises the patient's quality of life. Pharmacotherapy has been poorly studied in the MS population showing contradictory results and reduced compliance owing to intolerable side effects. A new neuromodulation technique known as percutaneous tibial nerve stimulation (PTNS) has shown good efficacy and safety in the treatment of neurogenic and non-neurogenic lower urinary tract symptoms. In this article we review the literature and critically summarise the scientific evidence supporting the use of PTNS in the treatment of lower urinary tract symptoms (LUTS) in patients with MS. METHODS: We performed a computer-aided literature search in PubMed and EMBASE up to January 2015 to identify randomised controlled trials, case-control trials and prospective observational cohort studies. RESULTS: A total of 7 open-label, prospective studies and 313 MS patients were included. Three studies reported clinical and urodynamic outcomes at 3 to 9 months after PTNS; one study assessed the long-term efficacy of PTNS; two studies reported the acute effect of PTNS on urodynamic findings; one study assessed whether motor and sensory responses during PTNS could predict treatment outcome. None of the studies included a control group. CONCLUSIONS: Despite the very limited data PTNS seems an effective and safe treatment option in the management of LUTS in patients with MS.

Cognitive rehabilitation correlates with the functional connectivity of the anterior cingulate cortex in patients with multiple sclerosis.

We investigated how resting state (RS) functional connectivity (FC) of the anterior cingulate cortex (ACC) correlates with cognitive rehabilitation in relapsing remitting multiple sclerosis (RRMS) patients. A neuropsychological assessment and RS fMRI at baseline and after 12 weeks were obtained from 20 RRMS patients, who were assigned randomly to undergo treatment (n = 10) (treatment group-TG), which entailed computer-assisted cognitive rehabilitation of attention/information processing and executive functions for 3 days/week, or not to receive any cognitive rehabilitation (n = 10) (control group-CG). Voxel-wise changes of ACC RS FC were assessed using SPM8. In both groups, at the two study time points, ACC activity was correlated with the bilateral middle and inferior frontal gyrus, basal ganglia, posterior cingulate cortex, cerebellum, precuneus, middle temporal gyrus, and inferior parietal lobule (IPL). At follow up, compared to baseline, the TG showed an increased FC of the ACC with the right middle frontal gyrus (MFG) and right IPL, while the CG showed a decreased FC of the ACC with the right cerebellum and right inferior temporal gyrus (ITG). A significant "treatment × time" interaction was found for the increased FC of the right IPL and for the decreased FC of the right ITG. In the TG only, significant correlations (p < 0.001) were found between improvement of PASAT performance and RS FC of the ACC with the right MFG (r = 0.88) and right IPL (r = 0.76). In MS, cognitive rehabilitation correlates with changes in RS FC of brain regions subserving the trained functions. fMRI might be useful to monitor rehabilitative strategies in MS.