Functional Connectivity Changes After Initial Treatment With Fingolimod in Multiple Sclerosis

On the basis of recent functional MRI studies, Multiple Sclerosis (MS) has been interpreted as a multisystem disconnection syndrome. Compared to normal subjects, MS patients show alterations in functional connectivity (FC). However, the mechanisms underlying these alterations are still debated. The aim of the study is to investigate resting state (RS) FC changes after initial treatment with fingolimod, a proven anti-inflammatory and immunomodulating agent for MS. We studied 32 right-handed relapsing-remitting MS patients (median Expanded Disability Status Scale: 2.0, mean disease duration: 8.8 years) who underwent both functional and conventional MRI with a 3 Tesla magnet. All assessments were performed 3 weeks before starting fingolimod, then, at therapy-initiation stage and at month 6. Each imaging session included scans at baseline (run1) and after (run2) a 25-min, within-session, motor-practice task, consisting of a paced right-thumb flexion. FC was assessed using a seed on the left primary motor cortex to obtain parametric maps at run1 and task-induced FC change (run2-run1). Comparison between 3-week before- and fingolimod start sessions accounted for a test-retest effect. The main outcome was the changes in both baseline and task-induced changes in FC, between initiation and 6 months. MRI contrast enhancement was detected in 14 patients at initiation and only in 3 at month 6. There was a significant improvement (p < 0.05) in cognitive function, as measured by the Paced Auditory Serial Addition Task, at month 6 compared to initiation. After accounting for test-retest effect, baseline FC significantly decreased at month 6, with respect to initiation (p < 0.05, family-wise error corrected) in bilateral occipito-parietal areas and cerebellum. A task-induced change in FC at month 6 showed a significant increment in all examined sessions, involving not only areas of the sensorimotor network, but also posterior cortical areas (cuneus and precuneus) and areas of the prefrontal and temporal cortices (p < 0.05, family-wise error corrected). Cognitive improvement at month 6 was significantly (p < 0.05) related to baseline FC reduction in posterior cortical areas. This study shows significant changes in functional connectivity, both at baseline and after the execution of a simple motor task following 6 months of fingolimod therapy

Functional Connectivity Changes After Initial Treatment With Fingolimod in Multiple Sclerosis

On the basis of recent functional MRI studies, Multiple Sclerosis (MS) has been interpreted as a multisystem disconnection syndrome. Compared to normal subjects, MS patients show alterations in functional connectivity (FC). However, the mechanisms underlying these alterations are still debated. The aim of the study is to investigate resting state (RS) FC changes after initial treatment with fingolimod, a proven anti-inflammatory and immunomodulating agent for MS. We studied 32 right-handed relapsing-remitting MS patients (median Expanded Disability Status Scale: 2.0, mean disease duration: 8.8 years) who underwent both functional and conventional MRI with a 3 Tesla magnet. All assessments were performed 3 weeks before starting fingolimod, then, at therapy-initiation stage and at month 6. Each imaging session included scans at baseline (run1) and after (run2) a 25-min, within-session, motor-practice task, consisting of a paced right-thumb flexion. FC was assessed using a seed on the left primary motor cortex to obtain parametric maps at run1 and task-induced FC change (run2-run1). Comparison between 3-week before- and fingolimod start sessions accounted for a test-retest effect. The main outcome was the changes in both baseline and task-induced changes in FC, between initiation and 6 months. MRI contrast enhancement was detected in 14 patients at initiation and only in 3 at month 6. There was a significant improvement (p &lt; 0.05) in cognitive function, as measured by the Paced Auditory Serial Addition Task, at month 6 compared to initiation. After accounting for test-retest effect, baseline FC significantly decreased at month 6, with respect to initiation (p &lt; 0.05, family-wise error corrected) in bilateral occipito-parietal areas and cerebellum. A task-induced change in FC at month 6 showed a significant increment in all examined sessions, involving not only areas of the sensorimotor network, but also posterior cortical areas (cuneus and precuneus) and areas of the prefrontal and temporal cortices (p &lt; 0.05, family-wise error corrected). Cognitive improvement at month 6 was significantly (p &lt; 0.05) related to baseline FC reduction in posterior cortical areas. This study shows significant changes in functional connectivity, both at baseline and after the execution of a simple motor task following 6 months of fingolimod therapy

Renal transplant from very old donors: how far can we go?

The organ shortage has led many transplant centers to accept kidneys from old, suboptimal deceased donors, and make increasing use of old-for-old allocation systems. We report the experience of an Italian transplant center in the utilization of "ultra-old" (>75 years old) donors. Methods. Sixty grafts from donors aged 75 years or older (mean age 79.1 years, range 75-90 years) were used for 38 patients: 16 as single and 22 as double transplants. Results. The actuarial graft survival rate was 73.7% for year 1, 69.8% for year 2, and 64.0% for year 3. The patient survival rate was 81.2% and remained stable for years 1, 2, and 3. The delayed graft function rate was 57.9%. Acute rejection and chronic allograft nephropathy rates were comparable with our other expanded criteria donors. The majority of the patients had stable creatinine levels, between 2 and 3 mg/mL after the second month, with sufficient creatinine clearance. Conclusions. Our results seems encouraging with patient and graft survival rates, complication rates, and renal function parameters being slightly worse than in expanded criteria donors, but still generally acceptable. The use of old kidneys in old recipients, bearing in mind their usual life expectancy, gives them a properly functioning kidney and improved quality of life

QTc interval diurnal variations in patients treated with psychotropic medications: implications for the evaluation of drug induced QTc changes

Psychotropic drugs such as antipsychotics may prolong the QTc interval, increasing the risk of torsades de pointes (TdP) and sudden cardiac death. To assess QTc prolongation by psychotropic drugs, an electrocardiogram (EKG) is usually recorded before and after starting treatment. Circadian variations in the QTc interval have been described but have not been adequately studied in patients taking psychotropic drugs. In psychiatric clinical practice, EKGs before and after treatment initiation are often compared, without considering the time of day at which the two EKGs are recorded. To determine whether there is a circadian change in the QTc interval in patients treated with psychotropic drugs, we evaluated the EKGs of a group of patients treated with psychotropic drugs (85% on antipsychotics) and the EKGs of a group of patients that were not treated with medications. In each group, we compared the EKGs recorded before 11:00 am with those recorded after 5:00 pm. The QTc value was significantly longer in the group treated with psychotropic drugs than in the group without drugs at both morning and evening evaluations (p ≤ 0.001). In each group, a statistically significant difference was found between the EKGs recorded before 11:00 a.m. and the EKGs recorded after 5:00 p.m. In patients treated with medications, the mean QTc in the morning was 453.3 ± 25.4 while the mean QTc in the afternoon was 428.4 ± 24.7 (p &lt; 0.0001). In patients who were not receiving any medication, the morning mean QTc was 422.4 ± 22.6 while the mean afternoon QTc was 409.4 ± 19.6 (p = 0.002). These results suggest that a circadian variation in QTc is observed both in patients taking psychotropic drugs and in patients not taking medication. We conclude that any comparison of EKGs to test the effect on QTc of a medication, should be referred to EKGs recorded at the same time of day