New pharmacological strategies in rheumatic diseases.

Targeting the pathogenic pathway of chronic inflammation represents an unmet challenge for controlling disease activity, preventing functional disability, and maintaining an adequate quality of life in patients with rheumatic diseases. Abatacept, a novel molecule that inhibits co-stimulation signal, induces an inhibitory effect on the T-cells. This will further interfere with the activity of several cell lines, leading to the normalization of the immune response. In the latest years, abatacept has been extensively investigated in studies of rheumatoid arthritis for which it was recently approved as a second line biologic treatment in Romania. This review presents the clinical efficacy of abatacept in several rheumatic diseases and highlights the safety profile of this biological agent. Abbreviations: ACR = American College of Rheumatology, ADR = Adverse drug reaction, APC = antigen presenting cell, ApS = psoriatic arthritis, CRP = C reactive protein, CTLA-4 = Cytotoxic T-Cell Lymphocyte Antigen-4, DAS = Disease activity score, DMARDs = Disease modifying antirheumatic drugs, EMA = European Medicine Agency, EULAR = European League Against Rheumatism, FDA = Food and Drugs Administration, HBV = Hepatitis B virus, JIA = Juvenile Idiopathic Arthritis, LDA = low disease activity (LDA), MRI = magnetic resonance imaging (MRI), MTX = methotrexate, RA = rheumatoid arthritis, RCT = randomized controlled trial, SS = Sjogren's syndrome, TCR = T cell receptor.

Plasmatic markers for early diagnostic and treatment decisions in ischemic stroke.

A neurologic deficit of sudden onset conforming to a vascular territory is a clear clinical indication that a patient suffers from an acute stroke. However, the imagistic diagnostic confirmation is not always readily available. We are now able to offer comprehensive medical support for the patient after an acute stroke and to make a prodigious rehabilitation program after the damage is done, but this is not offering the chance for improvement. An opportunity to better diagnose ischemic stroke seems to be available by using neuronal biomarkers. Extensive research is being conducted in this field and useful information is beginning to gather. This mini-review aims to highlight selected studies that appear to be of particular interest for the clinical neurologist. The most promising biomarkers (or rather panels of biomarkers) are presented with theirs clinical usefulness and limitations.

Low-frequency rTMS in patients with subacute ischemic stroke: clinical evaluation of short and long-term outcomes and neurophysiological assessment of cortical excitability.

RATIONALE: Repetitive transcranial magnetic stimulation (rTMS) is used alone or in combination with physiotherapy for rehabilitation of stroke patients. TMS mapping can also quantify the excitability of the motor area in both the ipsilesional (IL) and contralateral (CL) hemisphere. OBJECTIVE: This study is the first to measure the dynamics of cortical excitability by TMS mapping before and after treatment with low-frequency (LF) rTMS in the contralesional hemisphere at three different timepoints. Furthermore, the patients were clinically evaluated during the same visit as the mapping to establish both short and long-term outcomes after rTMS treatment. METHODS AND RESULTS: A total of 16 participants with acute ischemic stroke were assessed 10 days post-stroke by TMS mapping. The patients were randomized into two equal groups: a real rTMS group and a sham group. The rTMS group received LF-rTMS to the contralesional hemisphere for 10 days, starting on the first day after the first mapping. Each subject was also evaluated by mapping on days 45 and 90 after stroke onset. The primary clinical outcome measured was the Fugl-Meyer Assessment for Upper Extremity (FMA-UE) on days 10, 45 and 90 post-stroke. At 10 days after stroke onset, both groups presented low excitability in the lesion side and high excitability in the non-affected side. In the real rTMS group, at 45 days after stroke, a downward trend in the excitability of the contralesional hemisphere and an upward trend in the excitability of the lesioned side were observed. At 90 days after stroke, a tendency toward balanced excitability between both hemispheres was observed. In the sham group, at both 45 and 90 days, we observed increased excitability in the non-affected side compared to the side with the lesioned motor area. At 45 days, the real rTMS group demonstrated a better recovery of the upper limb motor function than the sham group, but at 90 days, there was no significant difference between the two groups. DISCUSSION: These results demonstrated that LF-rTMS treatment enhances rebalance of the excitability patterns in both hemispheres and led us to question the "one size fits all" approach widely used in rTMS interventions. ABBREVIATIONS: Amax = maximum amplitude, Amean = AM = averaged amplitude, APB = abductor pollicis brevis, CL = contralesional, DTI = diffusion tensor imaging, EEG = electroencephalography, EMG = electromyography, FMA-UE = Fugl-Meyer Assessment for Upper Extremity, HS = hot spot, IHC = interhemispheric functional connectivity, IL = ipsilesional, LF-rTMS = low-frequency repetitive transcranial magnetic stimulation, MCA = middle cerebral artery, MEP(s) = motor evoked potential(s), NIBS = non-invasive brain stimulation, rMT = resting motor threshold, RP = responsive points, rTMS = repetitive transcranial magnetic stimulation, TMS = transcranial magnetic stimulation.