Alterations in peripheral blood monocyte and dendritic cell subset homeostasis in relapsing-remitting multiple sclerosis patients.

Antigen-presenting cells participate and are implicated in the pathogenesis of multiple sclerosis. In our study we assessed the frequency of plasmacytoid (pDC) and myeloid (mDC) dendritic cells and the classical, intermediate and non-classical monocytes subsets, as well as their phenotypic and functional profile. We evaluated peripheral blood from relapsing-remitting patients treated with IFN-ß in remission and relapse phases and from healthy subjects. In remission, we observed a decrease of mDC/pDC ratio and a return to normal values in relapse. In both phases the frequency of non-classical monocytes decreases. Concerning the phenotypic characterization, an increased HLA-DR expression was observed in remission and a decrease in relapse, revealing alterations in monocytes and dendritic cells homeostasis.

Alterations in circulating T cell functional subpopulations in interferon-beta treated multiple sclerosis patients: A pilot study.

Our work consists of a pilot study to characterize circulating Th/c1, Th/c2, Th/c17, Treg and Tfh-like populations and IL-17 serum levels of relapsing-remitting (RR) MS patients treated with IFN-ß, compared with healthy controls. In remission RRMS patients, we observe increased Th/c17 cells frequency committed to a Th1 profile and increased soluble IL-17 levels. Moreover, a shift toward Th/c2 with reduction of Tc1 cells and decrease in effector/terminal differentiated compartment of Th1 cells were also observed. Despite RRMS patients being an inactive disease phase, IL-17 and Th/c17 cells seemed to contribute to perpetuating chronic inflammation, besides the altered ratio Th1/Th2.

Interferon-beta treated-multiple sclerosis patients exhibit a decreased ratio between immature/transitional B cell subset and plasmablasts.

Our aim was to quantify circulating B cell subsets; immature/transitional, naïve, CD27- and CD27+ memory cells and plasmablasts, in relapsing-remitting multiple sclerosis patients treated with IFN-ß. The most relevant findings were a significant increase of plasmablasts and a decrease of immature/transitional B cells, resulting in a decreased ratio between those cells in relapse RRMS, together with an increase of CD27- and CD27+IgM+ memory B cell subsets in both phases of the disease. These alterations point to an active B cell response, particularly in relapse, and the above referred ratio could constitute a good biomarker of relapse in patients that underwent IFN-ß treatment.

Characterization of circulating gamma-delta T cells in relapsing vs remission multiple sclerosis.

We characterized circulating gamma-delta T cells in relapsing-remitting multiple sclerosis (RRMS) patients, during remission and relapse phases. In relapse, we observed a decrease of circulating CCR5+ γδ TEMRA cell subset, together with a decrease in EOMES and granzyme B mRNA expression in γδ T cells, suggesting a reduction of the cytotoxic potential of this subset. Moreover, we also found a higher frequency of IFNγ+ γδ T cells, which may indicate that these cells are assuming a more regulatory function associated to a Th1 profile. These results suggest a specific release from the periphery of a particular γδ T cell subset, expressing CCR5 and belonging to an effector compartment, supporting the idea that γδ T cells could play a role in MS relapse.

Relative localizing value of amygdalo-hippocampal MR biometry in temporal lobe epilepsy.

OBJECTIVES: The aims of the study were (i) to examine the localizing value of three MRI quantitative modalities (qMRI) currently used for the analysis of the hippocampus and amygdala in the context of pre-surgical screening and (ii) to propose a step-by-step protocol based on the sensitivity and performance of the different MR techniques. METHODS: Ninety-two adults with chronic mesial temporal lobe epilepsy (TLE) of which 28 underwent amygdalo-hippocampal resection, and 34 age-matched controls were included in the study. High-resolution qMRI was performed at 1.5 T, including a tilted T1-weighted 3D-dataset for volumetry and four-echoes T2 relaxometry (both for hippocampus and amygdala quantifications) and multi-voxel spectroscopy [NAA/(Cho+Cre)] (exclusively in the hippocampus). Individual qMRI data were compared with electroencephalography regarding the localization of the epileptogenic area, with the neuropathological data and with postoperative outcome. MRI pathology was defined based on 99% confidence ellipses. Ten controls were used to assess the quantitative MRI intra- and inter-observer variability for all variables. RESULTS: Volumetric measurements revealed unilateral damage in 77% of the patients, T2-relaxometry in 64% and spectroscopy in 53%. Additional measurements of the amygdalae (T2-relaxometry) allowed us to localize pathology that coexists with that of the hippocampus in 34%, and isolated unilateral amygdala damage in 8% of patients. Volumetry and T2-relaxometry (not spectroscopy) were associated with postoperative outcome, but accurate predictive models were computed based on hippocampal measures only. At least at 1-year follow-up, volumetry predicts outcome correctly in 100% of the cases, whilst T2-relaxometry classified 96.4% (27/28) of these patients. All operated patients had hippocampal sclerosis. CONCLUSIONS: Hippocampal structural damage is equivocally depicted by spectroscopy. For diagnostic and pre-operative evaluation, hippocampal volumetry and T2-relaxometry provide maximal accuracy. Amygdala quantifications are irrelevant in the pre-operative evaluation but may be useful for diagnostic purposes. Of the three qMRI modalities tested, T2-relaxometry provided the best balance between diagnosis accuracy and time-efficiency to lateralize a sclerotic lesion on the majority of the patients. Cases that remain undecided after T2-relaxometry may benefit from additional measurements based on hippocampal volumetry.

[Impact of an active educational strategy in arterial hypertension]. / Impacto de una estrategia educativa activa participativa en el control de la hipertensión arterial.

OBJECTIVE: To evaluate the efficacy of an active-participative educational intervention on the average arterial pressure, index of corporal mass and level of knowledge in hypertensive patients. METHODS: A quasi-experimental open study was carried out. An active-participative educational intervention 4 h daily during a period of 5 days twice monthly for 3 months focused on themes related to arterial hypertension in patients with high blood pressure. No control subjects were included. Subject to acceptance and after informed consent, 48 patients (25-60 years of age) were included with slight and moderate arterial hypertension. Patients with evidence of severe organ damage or with chronic underlying disease were excluded. The impact of the educational intervention was evaluated based on the increase of knowledge, improvement of weight (IMC), and average arterial pressure, taking into consideration 2, 4, and 6 months of the educational strategy. Descriptive statistics were utilized for analyzing results using Student's ttest. RESULTS: The level of knowledge increased 31.30 points in the population studied and there was a decrease of the IMC of 2.75 points after educational intervention (p < 0.05). The decrease in weight, as well as the arterial pressure, showed statistically significant differences with respect to the initial measurements, with a difference of the PAM of 13.69 mm Hg at the conclusion of the study (p < 0.05). CONCLUSIONS: An active-participative educational strategy is useful in the control of the PAM and IMC in the hypertensive patient.

Liquid chromatographic assay based on microextraction by packed sorbent for therapeutic drug monitoring of carbamazepine, lamotrigine, oxcarbazepine, phenobarbital, phenytoin and the active metabolites carbamazepine-10,11-epoxide and licarbazepine.

A new, sensitive and fast high-performance liquid chromatography-diode-array detection assay based on microextraction by packed sorbent (MEPS/HPLC-DAD) is herein reported, for the first time, to simultaneously quantify carbamazepine (CBZ), lamotrigine (LTG), oxcarbazepine (OXC), phenobarbital (PB), phenytoin (PHT), and the active metabolites carbamazepine-10,11-epoxide (CBZ-E) and licarbazepine (LIC) in human plasma. Chromatographic separation of analytes and ketoprofen, used as internal standard (IS), was achieved in less than 15min on a C18-column, at 35°C, using acetonitrile (6%) and a mixture (94%) of water-methanol-triethylamine (73.2:26.5:0.3, v/v/v; pH 6.5) pumped at 1mL/min. The analytes and IS were detected at 215, 237 or 280nm. The method showed to be selective, accurate [bias ±14.8% (or ±17.8% in the lower limit of quantification)], precise [coefficient variation ≤9.7% (or ≤17.7% in the lower limit of quantification)] and linear (r(2)≥0.9946) over the concentration ranges of 0.1-15µg/mL for CBZ; 0.1-20µg/mL for LTG; 0.1-5µg/mL for OXC and CBZ-E; 0.2-40µg/mL for PB; 0.3-30µg/mL for PHT; and 0.4-40µg/mL for LIC. The absolute extraction recovery of the analytes ranged from 57.8 to 98.1% and their stability was demonstrated in the studied conditions. This MEPS/HPLC-DAD assay was successfully applied to real plasma samples from patients, revealing to be a cost-effective tool for routine therapeutic drug monitoring of CBZ, LTG, OXC, PB and/or PHT.

[EEG interictal--sensitivity and specificity of the diagnosis of epilepsy]. / Electroencefalograma interictal--sensibilidade e especificidade no diagnóstico de epilepsia.

EEG is a non invasive, cheap and accessible method, systematically used in the investigation of epilepsy. We present a review of studies regarding the prevalence of epileptiform abnormalities in epileptic and non-epileptic patients, with the objective of drawing conclusions about the specificity and sensitivity of the EEG in the diagnosis of epilepsy. We conclude that the sensitivity of the first EEG is 50-55%, although it can reach 92% with exam repetition and use of sleep records and activation techniques. The specificity of the EEG is influenced by many factors and reaches 96% in some epileptic syndromes.