The safety and efficacy of fingolimod: Real-world data from a long-term, non-interventional study on the treatment of RRMS patients spanning up to 5 years from Hungary.

BACKGROUND: Fingolimod was approved and reimbursed by the healthcare provider in Hungary for the treatment of highly active relapsing-remitting multiple sclerosis (RRMS) in 2012. The present study aimed to assess the effectiveness, safety profile, and persistence to fingolimod in a real-life setting in Hungary in RRMS patients who were either therapy naïve before enrollment or have changed to fingolimod from another disease-modifying therapy (DMT) for any reason. METHODS: This cross-sectional, observational study with prospective data collection was performed nationwide at 21 sites across Hungary. To avoid selection bias, sites were asked to document eligible patients in consecutive chronological order. Demographic, clinical, safety and efficacy data were analysed for up to 5 years from 570 consenting adult patients with RRMS who had received treatment with fingolimod for at least one year. RESULTS: 69.6% of patients remained free from relapses for the whole study duration; in the first year, 85.1% of patients did not experience a relapse, which rose to 94.6% seen in the 5th year. Compared to baseline at study end, 28.2% had higher, and 9.1% had lower, meanwhile, 62.7% of the patients had stable EDSS scores. Overall, the annualized relapse rate decreased from 0.804 observed at baseline to 0.185, 0.149, 0.122, 0.091, and 0.097 (77.0%, 82.1%, 85.2%, 89.7%, and 89.0% relative reduction, respectively) after 1, 2, 3, 4, and 5 years of treatment. The greatest reduction rate was seen in the group of therapy naïve patients. Treatment persistence on fingolimod after 60 months was 73.4%. CONCLUSION: In this nationwide Hungarian cohort, most patients under fingolimod treatment were free from relapses and disability progression. In addition, fingolimod has proven to be a well-tolerated DMT that has sustained its manageable safety profile, high efficacy, and positive benefit/risk ratio for up to 5 years in a real-life setting.

Implant for Augmentation of Cerebral Blood Flow Trial-1 (ImpACT-1). A single-arm feasibility study evaluating the safety and potential benefit of the Ischemic Stroke System for treatment of acute ischemic stroke.

BACKGROUND: The Ischemic Stroke System is a novel device designed to deliver stimulation to the sphenopalatine ganglion(SPG).The SPG sends parasympathetic innervations to the anterior cerebral circulation. In rat stroke models, SPG stimulation results in increased cerebral blood flow, reduced infarct volume, protects the blood brain barrier, and improved neurological outcome. We present here the results of a prospective, multinational, single-arm, feasibility study designed to assess the safety, tolerability, and potential benefit of SPG stimulation inpatients with acute ischemic stroke(AIS). METHODS: Patients with anterior AIS, baseline NIHSS 7-20 and ability to initiate treatment within 24h from stroke onset, were implanted and treated with the SPG stimulation. Patients were followed up for 90 days. Effect was assessed by comparing the patient outcome to a matched population from the NINDS rt-PA trial placebo patients. RESULTS: Ninety-eight patients were enrolled (mean age 57years, mean baseline NIHSS 12 and mean treatment time from stroke onset 19h). The observed mortality rate(12.2%), serious adverse events (SAE)incidence(23.5%) and nature of SAE were within the expected range for the population. The modified intention to treat cohort consisted of 84 patients who were compared to matched patients from the NINDS placebo arm. Patients treated with SPG stimulation had an average mRS lower by 0.76 than the historical controls(CMH test p = 0.001). CONCLUSION: The implantation procedure and the SPG stimulation, initiated within 24hr from stroke onset, are feasible, safe, and tolerable. The results call for a follow-up randomized trial (funded by BrainsGate; clinicaltrials.gov number, NCT03733236).

Probabilistic sequence learning in mild cognitive impairment.

Mild Cognitive Impairment (MCI) causes slight but noticeable disruption in cognitive systems, primarily executive and memory functions. However, it is not clear if the development of sequence learning is affected by an impaired cognitive system and, if so, how. The goal of our study was to investigate the development of probabilistic sequence learning, from the initial acquisition to consolidation, in MCI and healthy elderly control groups. We used the Alternating Serial Reaction Time task (ASRT) to measure probabilistic sequence learning. Individuals with MCI showed weaker learning performance than the healthy elderly group. However, using the reaction times only from the second half of each learning block-after the reactivation phase-we found intact learning in MCI. Based on the assumption that the first part of each learning block is related to reactivation/recall processes, we suggest that these processes are affected in MCI. The 24-h offline period showed no effect on sequence-specific learning in either group but did on general skill learning: the healthy elderly group showed offline improvement in general reaction times while individuals with MCI did not. Our findings deepen our understanding regarding the underlying mechanisms and time course of sequence acquisition and consolidation.

[Study of the effects of vinpocetin on cognitive functions]. / A vinpocetin kognitív funkciókra gyakorolt hatásának vizsgálata.

INTRODUCTION: Chronic cerebral hypoperfusion is a risk factor for the development of certain types of dementia. Mild cognitive impairment is a stage of predementia condition, because the symptoms are similar but not as severe as the symptoms in patients with dementia. Vinpocetine, due to its complex mechanism of action, has an important role in the improvement of chronic cerebral hypoperfusion. OBJECTIVES: The aim of our study was to determine the severity of the cognitive decline and to investigate the efficacy and safety of per os 18 months vinpocetine treatment in patients with mild cognitive impairment. METHODS: We used psychometrical tests (MMSE, ADAS-Cog) to assess the cognitive functions. CGIC-PGIC was used to evaluate the overall change in the disease status. ADL was used to assess the patient's daily activity and the Hamilton Depression Scale to evaluate the patient's mood. The assessments were performed at six visits during the 18 months treatment period. RESULTS: At the beginning of the treatment, the stage of our patients' mild cognitive impairment was moderately severe. Significant improvement was detected in the psychometrical tests after the 18 months treatment period. The overall status of the disease improved significantly according both to the patient and the investigator. Also significant improvement was detected in daily activity. The complex improvement of the clinical symptoms affected the patients' mood positively. Moreover, vinpocetine was safe and had a good tolerability during the whole study period. CONCLUSIONS: Vinpocetine, due its complex mechanism of action, improved significantly the cognitive functions, overall disease status and quality of life in patients with chronic cerebral hypoperfusion. As a result, vinpocetine treatment can be recommended for patients with mild cognitive impairment.

Prophylaxis of thrombotic and embolic events in acute ischemic stroke with the low-molecular-weight heparin certoparin: results of the PROTECT Trial.

BACKGROUND AND PURPOSE: Patients with stroke are at substantial risk of thromboembolic complications and therefore require antithrombotic prophylaxis. To show the noninferiority of the low-molecular-weight heparin certoparin to unfractionated heparin (UFH) for the prevention of thromboembolic complications, we performed a randomized, double-blind, active-controlled multicenter trial in patients with acute ischemic stroke. METHODS: Overall, 545 patients were randomized within 24 hours of stroke onset to treatment with certoparin (3000 U anti-Xa OD; n=272) or UFH (5000 U TID; n=273) for 12 to 16 days. Patients with paresis of a leg and an National Institutes of Health Stroke Scale score of 4 to 30 points were included. The primary end point was a composite outcome of proximal deep vein thrombosis, pulmonary embolism, or death related to venous thromboembolism during treatment. Computed tomography was performed at trial entry, after 7 days, and when clinical deterioration occurred. RESULTS: The per-protocol analysis revealed 17 (7.0%) primary events in the certoparin group compared with 24 (9.7%) in the UFH group, thereby demonstrating noninferiority (P=0.0011), confirmed by intention-to-treat analysis (6.6% versus 8.8%; P=0.008). Major bleeding occurred during treatment in 3 patients allocated to certoparin (1.1%) and 5 patients allocated to UFH (1.8%). CONCLUSIONS: Certoparin (3000 U anti-Xa OD) is at least as effective and safe as UFH (TID) for the prevention of thromboembolic complications in patients with acute ischemic stroke.

Serum semicarbazide-sensitive amine oxidase (SSAO) activity is an independent marker of carotid atherosclerosis.

BACKGROUND: Clinical and experimental studies suggest that increased activity of semicarbazide-sensitive amine oxidase (SSAO) and the production of cytotoxic metabolites (e.g., formaldehyde and hydrogen peroxide) may play an important role in the pathogenesis of atherosclerosis. The present study was designed to assess the relationship between the increased activity of the enzyme and the severity of atherosclerosis in diabetic and control subjects. METHODS: The study included 29 patients with type 2 diabetes mellitus and 25 control subjects. Human serum SSAO activity was determined by using 14C-benzylamine as substrate. Mean common carotid intima-media thickness (IMT), Crouse score and Bogousslawsky score was evaluated by color-coded, high-resolution duplex carotid sonography. RESULTS: Serum SSAO activity was significantly increased in patients with type 2 diabetes compared to controls. Carotid plaque score (Crouse score), total cholesterol level and age-corrected intima-media thickness showed positive correlation with enzyme activity in control subjects. In patients with diabetes, serum SSAO activity correlated with the severity of carotid stenosis (Bogousslawsky score) as well as the carotid plaque score. CONCLUSIONS: Determination of serum SSAO activity might be a candidate biochemical marker of early atherosclerosis and diabetic macrovascular complications.