The number of circulating monocytes increases after stroke. In this study, we assessed the time course and phenotype of monocyte subsets and their relationship with the clinical course and outcome in 46 consecutive stroke patients and 13 age-matched controls. The proportion of the most abundant ‘classical’ CD14^highCD16 monocytes did not change after stroke, whereas that of CD14^highCD16+ monocytes increased and CD14^dimCD16+ monocytes decreased. CD14^highCD16 + monocytes had the highest expression of TLR2, HLA-DR and the angiogenic marker, Tie-2; CD14^dimCD16+ monocytes had the highest expression of costimulatory CD86 and adhesion molecule CD49d. Platelet-monocyte interactions were highest in CD14^highCD16 monocytes and lowest in CD14^dimCD16+ monocytes. In adjusted models, 1/CD14^highCD16 monocytes were associated with poor outcome (OR: 1.38), higher mortality (OR: 1.40) and early clinical worsening (OR: 1.29); 2/CD14^highCD16+ monocytes were inversely related to mortality (OR: 0.32); and 3/CD14^dimCD16+ monocytes were inversely related to poor outcome (OR: 0.74) and infarction size ( r= 0.45; P = 0.02). These results illustrate that the predominant monocyte subtype conveys harmful effects after stroke, which include stronger interaction with platelets. Alternatively, rarer subpopulations of monocytes are beneficial with a phenotype that could promote tissue repair and angiogenesis. Therefore, monitoring of monocyte subtypes may emerge as a useful tool at the bedside for stroke patients.

In experimental animals, the presence of brain-derived constituents in cervical lymph nodes has been associated with the activation of local lymphocytes poised to minimize the inflammatory response after acute brain injury. In this study, we assessed whether this immune crosstalk also existed in stroke patients. We studied the clinical course, neuroimaging, and immunoreactivity to neuronal derived Ags (microtubule-associated protein-2 and N-methyl d-aspartate receptor subunit NR-2A), and myelin-derived Ags (myelin basic protein and myelin oligodendrocyte glycoprotein) in palatine tonsils and cervical lymph nodes of 28 acute stroke patients and 17 individuals free of neurologic disease. Stroke patients showed greater immunoreactivity to all brain Ags assessed compared with controls, predominantly in T cell zones. Most brain immunoreactive cells were CD68+ macrophages expressing MHC class II receptors. Increased reactivity to neuronal-derived Ags was correlated with smaller infarctions and better long-term outcome, whereas greater reactivity to myelin basic protein was correlated with stroke severity on admission, larger infarctions, and worse outcome at follow-up. Patients also had more CD69+ T cells than controls, indicative of T cell activation. Overall, the study showed in patients with acute stroke the presence of myelin and neuronal Ags associated with lymph node macrophages located near activated T cells. Whether the outcome of acute stroke is influenced by Ag-specific activation of immune responses mediated by CD69 lymphocytes deserves further investigation.

Background and Purpose—: Uric acid (UA) is a neuroprotective antioxidant that improves the benefits of alteplase in experimental ischemia. However, it is unknown whether endogenous UA also influences the response to thrombolysis in patients with stroke. Methods—: A total of 317 consecutive patients treated with thrombolysis were included in a prospective stroke registry. Demographics, laboratory data, neurological course, and infarction volume were prospectively collected. Excellent outcome was defined as achieving a modified Rankin Scale score <2 at 90 days. Binary and ordinal logistic regression models were used to analyze modified Rankin Scale score at 90 days. Results—: UA levels were significantly higher in patients with an excellent outcome than in patients with a poor outcome (5.82 [1.39] versus 5.42 [1.81], P =0.029). In multivariate models, increased UA levels (OR, 1.23; 95% CI, 1.03 to 1.49; P =0.025) were associated with an excellent outcome and with an increased risk of shifting to a better category across the modified Rankin Scale (OR, 1.19; 95% CI, 1.04 to 1.38; P =0.014) independently of the effect of confounders. The levels of UA and the volume of final infarction were inversely correlated ( r =−0.216, P <0.001) and the inverse correlation remained after adjustment for age, sex, and baseline National Institutes of Health Stroke Scale score (t value=−2.54, P =0.01). Significantly lower UA levels were found in patients with malignant middle cerebral artery infarction and parenchymal hemorrhage postthrombolysis. Conclusions—: Increased UA serum levels are associated with better outcome in patients with stroke treated with reperfusion therapies. These results support the assessment of the potential neuroprotective role of the exogenous administration of UA in patients with stroke treated with thrombolysis.

A total of 135 consecutive, unrelated, multiple sclerosis (MS) patients were interviewed for symptoms suggestive of restless legs syndrome (RLS) and REM sleep behavior disorder (RBD), using semi-structured questionnaires. Some 118 unrelated healthy controls of similar sex and age distribution were included for comparison. Patients and controls with equivocal symptoms were re-evaluated by a sleep disorders specialist and video-polisomnography in those who fulfilled the criteria for RBD. We did not find significant differences in frequency (13.3 versus 9.3%), proportion of females (66.7 versus 58.5%), and mean age (42.1±12.6 versus 43±7.8 years) among MS patients and controls with RLS. RBD was found in three patients (1.4%), one associated with antidepressant intake, but in none of the controls. Our study shows that RLS in MS is not more frequent than in the general population, and that RBD, although uncommon, may occur in the setting of this neurological disease. Multiple Sclerosis 2007; 13: 805-808. http://msj.sagepub.com