Reduced Expression of PD-1 in Circulating CD4+ and CD8+ Tregs Is an Early Feature of RRMS.

Altered regulatory T cell (Treg) function could contribute to MS. The expression of activating and inhibitory receptors influences the activity of Tregs. Our aim was to investigate T cell phenotypes in relapsing-remitting MS (RRMS) patients at an early phase of the disease. We examined the influence of demographic parameters on the distribution of CD4+ and CD8+ T cell subclasses by generalized linear modeling. We also studied the expression of the following markers-CTLA-4, GITR, PD-1, FoxP3, Helios, CD28, CD62L, CD103-on T cell subsets from peripheral blood with a 14-color flow cytometry panel. We used an antibody array to define the profiles of 34 Th1/Th2/Th17 cytokines in the serum. Expression of PD-1 and GITR on CD4+ and CD8+ Tregs was decreased in RRMS patients. The proinflammatory factors IFN-γ, IL-17, IL-17F, TGFß-1, TGFß-3, IL-1SRII, IL-12 p40, sgp130, IL-6sR were significantly increased in RRMS patients. Therefore, a deficiency of PD-1 and GITR immune checkpoints on CD4+ and CD8+ Tregs is a feature of RRMS and might underlie impaired T cell control.

The activity of malignancy may determine stroke pattern in cancer patients.

BACKGROUND: It has been suggested that stroke in patients with cancer may differ from the conventional pattern. The aim of this study was to evaluate the burden of vascular risk factors, stroke etiology, and short-term outcome in patients with active and nonactive malignancy compared with patients without cancer. METHODS: This is a prospective cohort study of consecutive acute stroke patients admitted to our department between September 2006 and September 2011. We distinguished between the following: (1) patients with active malignancy (AM, diagnosed not earlier than 12 months before stroke); (2) patients with nonactive malignancy (non-AM); and (3) cancer-free (CF) patients, used as a reference. RESULTS: Pre-existing cancer was found in 90 of 1558 patients, including 41 (2.6%) cases with AM and 49 (3.1%) cases with non-AM. Compared with CF patients, AM patients less frequently had a history of previous stroke (2.4% versus 17.9%, P = .018) and more frequently experienced ischemic strokes of undetermined etiology (62.5% versus 38.3%, P = .002). Non-AM patients did not differ in the distribution of vascular risk factors but more often experienced stroke caused by small vessel occlusion (20.0% versus 8.0%, P = .004). Inflammatory blood markers were elevated especially in patients with AM. Short-term prognosis was similar across all groups. CONCLUSIONS: Stroke pattern in patients with non-AM appears very similar to that observed in the CF patients. However, our findings support the thesis that cancer-specific prothrombotic mechanisms play an important role in stroke patients with AM, which may be related to active inflammatory and immune processes. Malignancy does not influence short-term prognosis of stroke.

Validity of EQ-5D-5L in stroke.

PURPOSE: To assess EQ-5D-5L (5L) validity in patients with acute stroke, in comparison with EQ-5D-3L (3L). METHODS: Cross-sectional study of 408 patients during index hospitalization. We compared 5L and 3L in terms of feasibility, frequency of unique health states, ceiling effect and discriminatory power (informativity). We assessed construct validity in terms of known-groups validity and convergent validity of 5L dimensions with other stroke outcome measures. RESULTS: The overall proportion of patients with acute stroke reporting 'no problems' with 3L-6.1 % was further reduced to 5.6 % with 5L (relative reduction of 8.2 %). The highest improvement in relative discriminatory power, when moving from 3L to 5L, was noticed in pain/discomfort and anxiety/depression dimensions (Shannon Evenness Index 0.91 for both 5L dimensions; relative increase 34.4 and 29.1 %, respectively). Known-groups validity tests confirmed prior hypotheses: Health state utilities were lower in following subpopulations-females, patients with high modified Rankin Scale (mRS) score, low Barthel Index (BI) or VAS score, patients with subarachnoid hemorrhage or intracerebral hemorrhage, and when proxy respondent was used. Convergence of EQ-5D-5L dimensions with mRS, BI and EQ VAS was improved or at least the same as for 3L dimensions. CONCLUSIONS: Results support the validity of the EQ-5D-5L descriptive system as a generic health outcome measure in patients with acute stroke, demonstrating some psychometric advantages in comparison with EQ-5D-3L.

Comparing responsiveness of the EQ-5D-5L, EQ-5D-3L and EQ VAS in stroke patients.

AIMS: To date, evidence to support the construct validity of the EQ-5D-5L has primarily focused on cross-sectional data. The aims of this study were to examine the responsiveness of EQ-5D-5L in patients with stroke and to compare it with responsiveness of EQ-5D-3L and visual analogue scale (EQ VAS). METHODS: We performed an observational longitudinal cohort study of patients with stroke. At 1 week and 4 months post-stroke, patients were assessed with modified Rankin Scale (mRS) and Barthel Index (BI) and were administered the EQ-5D-5L and EQ-5D-3L, including the EQ VAS. The EQ-5D-5L index scores were derived using the crosswalk methodology developed by the EuroQol Group. We classified patients according to two external criteria, based on mRS or BI, into 3 categories: 'improvement,' 'stable' or 'deterioration'. We assessed the responsiveness of each measure in each patient subgroup using: effect size (ES), standardized response mean (SRM), F-statistic, relative efficiency and area under the receiver operating characteristic curve. RESULTS: A total of 112 patients (52% females; mean age 70.6 years; 93% ischemic stroke) completed all the instruments at both occasions. In subjects with clinical improvement, EQ-5D-5L was consistently responsive, showing moderate ES (0.51-0.71) and moderate to large SRM (0.69-0.86). In general, EQ-5D-3L index appeared to be more responsive (ES 0.63-0.82; SRM 0.77-1.06) and EQ VAS less responsive (ES 0.51-0.65; SRM 0.59-0.69) than EQ-5D-5L index. CONCLUSIONS: The EQ-5D-5L index, based on the crosswalk value set, seems to be appropriately responsive in patients with stroke, 4 months after disease onset. As far as EQ-5D-5L index is scored according to crosswalk approach, the EQ-5D-3L index appears to be more responsive in stroke population.

Positivity of serum "classical" onconeural antibodies in a series of 2063 consecutive patients with suspicion of paraneoplastic neurological syndrome.

This study determined the prevalence of classical onconeural Ab in a series of 2063 consecutive patients that were investigated because of suspicion of PNS as well as evaluated individual onconeural Ab in relationship to the clinical spectrum of associated neurological syndromes and tumor types detected in 70 patients finally diagnosed with PNS. We conclude that detectability of onconeural Ab is low among patients suspected with PNS. Specification of Ab is helpful in defining a neurological syndrome as paraneoplastic as well as in searching of underlying tumor. The success in tumor screening depends on the type of onconeural Ab.