Factors Associated with Severe Carotid Artery Stenosis in a Population with One of the Highest Incidences of Ischemic Stroke in Europe - Single National Center Analysis.

Introduction: Despite significant advances in its prevention and acute-phase treatment, stroke is still one of the leading causes of disability and death worldwide. Ischemic stroke accounts for 80 to 87% of all strokes, with 15-30% of cases being caused by extracranial carotid artery (CA) stenosis. Methods: This is an observational, cross-sectional, single-center, prospective, registry-based study. The current research presents the preliminary results after analyzing the demographic features, biological data, and cardio- and cerebro-vascular risk factors of the first 74 patients included in the first "Romanian registry for cervical and cerebral arterial stenosis." Results: In our group of patients, the severity of carotid artery stenosis was related to fibrinogen, total cholesterol, and triglyceride blood levels. Moreover, patients who underwent carotid artery stenosis were more prone to having peri-procedural complications if they had a low blood platelet count. Concerning the associated pathologies of patients with severe carotid atheromatosis, the risk of having lower cognitive abilities was higher in subjects with atrial fibrillation, regardless of the severity of carotid artery stenosis. Conclusions: The presented study brings essential information about a population more prone to cerebral ischemic events than that of most other countries. All data obtained until this moment and which will further result from analyzing the clinical, demographic, and biological features of patients included in this registry should be used for implementing populational strategies for preventing further strokes.

The effect of levodopa-carbidopa intestinal gel infusion long-term therapy on motor complications in advanced Parkinson's disease: a multicenter Romanian experience.

Chronic treatment with oral levodopa is associated with an increased frequency of motor complications in the late stages of Parkinson's disease (PD). Continuous administration of levodopa-carbidopa intestinal gel (LCIG-Duodopa(®), Abbott Laboratories), which has been available in Romania since 2009, represents an option for treating patients with advanced PD. Our primary objective was to report changes in motor complications after initiation of LCIG therapy. The secondary objectives were as follows: to determine the impact of LCIG therapy on the daily levodopa dose variation before/and after LCIG, to collect patient self-assessments of quality of life (QoL), and to study the overall tolerability and safety of LCIG administration. A retrospective analysis (2009-2013) of LCIG therapy and the experience in nine neurology centers in Romania was performed. The impact of LCIG therapy was evaluated by analyzing changes in motor fluctuations, dyskinesia and the patients' QoL after initiating therapy. The safety of LCIG therapy was estimated by noting agent-related adverse events (AEs) and medical device-related AEs. In the 113 patients included, we observed a significant improvement in PD symptoms after initiation of LCIG therapy. The "on" period increased, with a mean value of 6.14 h, and the dyskinesia period was reduced, with a mean value of 29.4 %. The quantified non-motor symptoms subsided. The patients exhibited significant improvements in QoL scores. There were few AEs and few cases of LCIG therapy discontinuation. LCIG is an important and available therapeutic option for managing patients with advanced PD.

Investigating motor imagery tasks by their neural effects - A case study.

Motor imagery, one of the first investigated neural process for Brain-Computer Interfaces (BCIs) still provides a great challenge nowadays. Aiming a better and more accurate control, multiple researches have been conducted by the scientific community. Nevertheless, there is still no robust and confident application developed. In order to augment the potential referring to motor imagery, and to attract user's interest, we propose multiple motor imagery tasks in combination with different visual or auditory stimuli. We use multi-class classification for discrimination and we observe confident classification performance for the task related to user's background.

Why antiplatelet treatment in spontaneous internal carotid dissection?

Spontaneous dissection of the internal carotid artery is a leading cause of stroke and TIA, particularly in young patients. The antithrombotic treatment with or without an interventional procedure is a unanimously accepted indication for the prevention of the ischemic events in these patients. Whether anticoagulants or antiplatelets as antithrombotics are a better option is a matter of debate. The authors, based on clinical and pathophysiological data in the published studies and their own experience argue in favour of antiplatelets in most cases, without excluding the need of anticoagulants in some cases, due to the lack of objective proofs for the superiority of anticoagulants in this pathology and at the same time, a better safety profile of antiplatelets. To have a clear-cut answer to this debate, a large comparative randomized clinical trial between the two types of treatment is desirable.

Efficacy and safety of Cerebrolysin in patients with hemorrhagic stroke.

UNLABELLED: The purpose of the study was to investigate the efficacy and safety of Cerebrolysin in patients with hemorrhagic stroke. The primary objective of this trial was to assess the clinical efficacy and safety of a 10-days course of therapy with a daily administration of Cerebrolysin (50 mL i.v. per day). The trial had to demonstrate that Cerebrolysin treatment is safe in hemorrhagic stroke. METHODS: The study was performed as a prospective, randomized, double blind, placebo-controlled, parallel group study with 2 treatment groups. Efficacy measures were the Unified Neurological Stroke Scale, Barthel Index, and Syndrome Short Test. The duration of the trial was of 21 days for each patient. Out of 100 randomized patients, a total of 96 (96%) completed the study. RESULTS: Overall, no statistically significant group effects were observed based on single average comparisons at the individual visits. It could be shown that the treatment of hemorrhagic stroke with Cerebrolysin is safe and well tolerated. CONCLUSION: In the changes of UNSS, BI and SST from baseline to day 21, the group differences are not statistically significant; however, the use of Cerebrolysin in hemorrhagic stroke is safe and well tolerated and studies with a larger sample size may provide statistical evidence of Cerebrolysin's efficacy in patients with hemorrhagic stroke.

[Video-assisted thoracoscopic extended thymectomy (VATET) with cervical approach for myasthenia gravis--initial experience]. / Timectomia extinsa prin abord toracoscopic bilateral si timp cervical pentru miastenia gravis--experienta initiala.

Complete thymectomy plays an important role in the myasthenia gravis (MG) pacient's treatment. Many different surgical techniques have been developed to achieve thymectomy. Of these, thoracoscopic technique is the most recent. There still are many controversies about the most suitable approach for thymectomy. The paper presents in detail the video-assisted thoracoscopic extended thymectomy--VATET-technique, and initial results with this procedure. Prospective data was obtain according to the Myasthenia Gravis Foundation of America (MGFA) recommendations. From Mai 2007 to December 2009, 15 patients with MG underwent the VATET procedure with cervical access. There was no conversion to sternotomic approach. Mean operating time for complete VATET was 215 min (150-280 min), with the cervical procedure requiring 44 min (25-60 min). There was no mortality or intraoperative complications. It was a single case with a thoracoscopic second look for hemothorax from intercostals bleeding. At this time, due to the reduced number of cases, we can't evaluate the therapeutic effectiveness of the VATET. We consider VATET as a valuable surgical option to treat myasthenic patients, with an optimal report between radicality and invasiveness.

Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Glatiramer acetate, approved for the treatment of relapsing-remitting multiple sclerosis, reduces relapses and disease activity and burden monitored by MRI. We assessed the efficacy of early treatment with glatiramer acetate in delaying onset of clinically definite multiple sclerosis. METHODS: In this randomised, double-blind trial, undertaken in 80 sites in 16 countries, 481 patients presenting with a clinically isolated syndrome with unifocal manifestation, and two or more T2-weighted brain lesions measuring 6 mm or more, were randomly assigned to receive either subcutaneous glatiramer acetate 20 mg per day (n=243) or placebo (n=238) for up to 36 months, unless they converted to clinically definite multiple sclerosis. The randomisation scheme used SAS-based blocks stratified by centre, and patients and all personnel were masked to treatment assignment. The primary endpoint was time to clinically definite multiple sclerosis, based on a second clinical attack. Analysis was by intention to treat. A preplanned interim analysis was done for data accumulated from 81% of the 3-year study exposure. This study was registered with ClinicalTrials.gov, number NCT00666224. FINDINGS: All randomly assigned participants were analysed for the primary outcome. Glatiramer acetate reduced the risk of developing clinically definite multiple sclerosis by 45% compared with placebo (hazard ratio 0.55, 95% CI 0.40-0.77; p=0.0005). The time for 25% of patients to convert to clinically definite disease was prolonged by 115%, from 336 days for placebo to 722 days for glatiramer acetate. The most common adverse events in the glatiramer acetate group were injection-site reactions (135 [56%] glatiramer acetate vs 56 [24%] placebo) and immediate post-injection reactions (47 [19%] vs 12 [5%]). INTERPRETATION: Early treatment with glatiramer acetate is efficacious in delaying conversion to clinically definite multiple sclerosis in patients presenting with clinically isolated syndrome and brain lesions detected by MRI. FUNDING: Teva Pharmaceutical Industries, Israel.

The results of two multicenter, open-label studies assessing efficacy, tolerability and safety of protiramer, a high molecular weight synthetic copolymeric mixture, in patients with relapsing-remitting multiple sclerosis.

OBJECTIVE: Two pilot studies were conducted to evaluate safety, tolerability, and efficacy of two doses of Protiramer (TV-5010) in patients with relapsing-remitting multiple sclerosis. BACKGROUND: Both glatiramer acetate and TV-5010 are synthetic copolymers comprised the same four amino acids in a defined molar ratio. TV-5010 has higher average molecular weight than Glatiramer acetate and might be hypothesized that glatiramoids with higher molecular weight might be more immunoreactive than lower molecular weight peptides, thus increasing therapeutic potential and allowing for less frequent dosing. METHODS: In the two separate studies, after a 10 week pretreatment period, TV-5010 was given subcutaneously once weekly at 15 mg and 30 mg for 36 weeks. The primary end point was a reduction in the number of magnetic resonance imaging active lesions (i.e., T1-weigthed gadolinium-enhancing and new T2-weighted lesions) between the pretreatment period and the end of study. RESULTS: Both TV-5010 doses were generally well tolerated. The treatment with TV-5010 at a dose of 15 mg/wk did not show any significant effect. In contrast, in patients treated with at a dose of 30 mg/wk, a significant reduction in the mean number of gadolinium-enhancing (-58.8%; P = 0.0013) and new T2-W (-50%; P = 0.0002) lesions was observed. However, a large decrease in the mean number of both gadolinium-enhancing (-55%) and new T2-W (-40%) lesions during the pretreatment period made difficult the interpretation of the efficacy assessments. CONCLUSIONS: Further studies are needed to confirm these preliminary data on safety and efficacy of TV-5010 at a weekly dose of 30 mg.

Dantrolene protects neurons against kainic acid induced apoptosis in vitro and in vivo.

Apoptotic cell death induced by kainic acid (KA) in cultures of rat cerebellar granule cells (CGC) and in different brain regions of Wistar rat pups on postnatal day 21 (P21) was studied. In vitro, KA (100-500 microM) induced a concentration-dependent loss of cell viability in MTT assay and cell death had apoptotic morphology as studied by chromatin staining with propidium iodide (PI). In vivo, twenty-four hours after induction of status epilepticus (SE) by an intraperitoneal KA injection (5 mg/kg) we quantified apoptotic cells in hippocampus (CA1 and CA3), parietal cortex and cerebellum using PI staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) technique. We report that dantrolene, a specific ryanodine receptor antagonist, was able to significantly reduce the apoptotic cell death in CGC cultures and in hyppocampal CA1 and parietal cortex regions. Our finding can be valuable for neuroprotective therapy strategies in patients with repeated generalized seizures or status epilepticus.

Effects of muscimol or homotaurine on sleep-wake states in alcohol-dependent rats during withdrawal.

Sleep-wake states were studied following withdrawal in 36 adult male wistar alcohol-dependent rats, after chronic administration of ethanol (10 g/kg/24 h) for 13 days. In the light phase of the withdrawal day, 12 alcohol-dependent rats received muscimol (0.25 mg/kg), 12 received homotaurine (140 mg/kg), and 12 received 0.9% physiological saline (10 ml/kg). The results have been compared with a control group of 36 rats that received water during the treatment phase of the experiment, and the 14th day received intraperitoneal muscimol or homotaurine. Muscimol significantly improves the alterations of sleep-wake states in alcohol-withdrawn rats, decreasing the percentage of active wakefulness and increasing the percentage of REMS, but without any action on the latency of appearance of REMS, which remains shortened. The effects of homotaurine are less important on the wakefulness, but it also increases the percentage of REMS without influencing its latency of appearance. The influence of these GABA(A) agonists is not identical during the whole period of survey in the light phase, as there are important differences in the temporal sequences for each of them. We conclude that the stimulation of GABA(A) receptors, of which the activity is decreased during alcohol withdrawal, significantly improves the disturbances in the sleep-wake states in the alcohol-dependent rats, in a time-related manner, and there are significant pharmacodynamic differences between muscimol and homotaurine.

Stability of brain content of magnesium in experimental hypomagnesemia.

Magnesium is important in cerebral function. If there is a deficiency and neurological symptoms accrue, we hypothesised that Mg2+ deficiency causes neurological symptoms by decreasing the level of Mg2+ in cerebral tissue. The content of magnesium was determined in 12 brain structures in magnesium-deficient rats. Experiments were carried out for 40 days in two groups of Wistar male rats made magnesium-deficient (MD) by a well-controlled diet (50 mg of Mg2+/kg of food), and a control group (CG) rats fed normal diet (1 g of Mg2+/kg of food). At the end of the 40 days, the clinical signs of hypomagnesemia were sought in the MD rats and Mg2+ concentration levels were measured in the blood and brain. The results showed variable distribution of Mg2+ in the different brain structures, both in CG and MD rats; in the MD rats there is an important stability of global Mg2+ content of the brain. Although the global values for Mg2+ in the brain did not decline in MD rats, there was a significant decrease in Mg2+ in the brainstem. We conclude that the brain is able to maintain a stable concentration of Mg2+ during chronic hypomagnesemia, but its topographic variations could account for some of neurological signs accompanying this condition.

The perception threshold to an electric stimulus deeply applied in the lower limbs in normal and diabetic subjects.

The loss of sensitivity to nociceptive stimuli is one of the main factors involved in the pathogeny of diabetic gangrene. The aim of this study was to develop a simple and practical method for selecting the cases prone to such a complication. The perception threshold (either voltage, mV or current, microA) was determined in 137 randomly selected diabetic patients and 38 non-diabetic controls, by an original electronic device using sinusoidal waves, delivered through two electrode needles introduced at a depth of 0.5 cm at two points located on the anterior aspect of the shank about 12 cm apart. At each of the eight frequencies studied (10, 20, 50, 100, 200, 500, 1000 and 2000 Hz) three electrical parameters (voltage across the needle electrodes, the resistive and the capacitive current component) were recorded when the subject first perceived the stimulus. A significantly higher perception threshold was found in diabetic patients vs. non-diabetic subjects, at all frequencies studied and with all three electrical parameters recorded. A greater difference in the perception threshold between diabetic and non-diabetic subjects (a ratio higher than 3) was, however, found using the resistive component of the current and at frequencies higher than 200 Hz.

Evaluation in autonomic diabetic neuropathy using a dual-channel self-balancing impedance reactometer. Preliminary study.

The electrodermal reflex to an external acoustic stimulus was determined by means of an original device "'The Neurovegetative Reactometer", as variation of the skin electric resistance delta R/R (recorded on millimetric paper) and latency in the appearance of the response (seconds), in 39 diabetic patients (20 males, 19 females, aged 55 +/- 10 years, and the duration of diabetes of 6 +/- 4 years) with or without clinical neuropathy and, comparatively, in 24 apparently healthy controls. The results showed a statistically significant difference both between the amplitude of the skin electric resistance variation evaluated on millimetric paper (6.77 +/- 4.06 mm versus 22.79 +/- 5.39 mm in the controls, p less than 0.001) and latency (4.29 +/- 1.55 versus 2.49 +/- 0.57 seconds, p less than 0.001). These two parameters reflect quantitatively the skin sympathetic activity in lower limbs. The results obtained recommend neurovegetative reactometry as a practical, non-invasive, rapid and readily applicable method, which is highly technical and sensitive for evaluating autonomic dysfunction in diabetic neuropathy.

Study of the cutaneous electric potentials and the perception threshold to an electric stimulus in diabetic patients with and without clinical neuropathy.

Clinical heterogeneity of diabetic peripheral neuropathy could express a neurophysiological and electrophysiological heterogeneity possibly related with the dissociated metabolic susceptibility of the difference types of nerve fibres and endings. To evaluate the functional status of the skin autonomous nervous system and of the deep pain sensitivity system in diabetics we studied two electrophysiological parameters skin electrical potential (using Digital Multimeter 3466 Hewlet Packard, USA) and the perception threshold (microA) at an electrical stimulus (spike wave, 0.5 m sec duration) 1 cm deeply applied through 2 acupuncture needles placed 30 cm distance each other, in 3 groups: Ia-18 diabetic patients with clinical signs of neuropathy (12 M, 6 F, aged 55 +/- 17 yrs); Ib - 17 diabetic patients without clinical signs of diabetic neuropathy (12 M, 5 F, aged 57 +/- 16 yrs); I1 - 10 age and sex matched non-diabetic controls. Our data show: a higher mean value of the potential in the acupuncture points as against neighbour areas, both in non-diabetic control (- 111 +/- 25 mV v.s. -81 +/- 29 mV, p less than 0.05) and in diabetics (-85 +/- 43 mV v.s. -58 +/- 25 mV, p less than 0.01); a lower mean value of the electrical potentials in diabetic with clinical signs of neuropathy as against in those without clinical signs of neuropathy (-66 +/- 29 mV v.s. -108 +/- 43 mV, p less than 0.01): a higher mean value of the perception threshold in diabetics with clinical signs of neuropathy as against in diabetics without clinical signs of neuropathy (213 +/- 82 microA. v.s. 102 +/- 40 microA, p less than 0.01); a significant correlation (r = -0.81) between the perception threshold and the electrical potentials of the studied points.