Objective
We conducted a randomized, double‐blind, placebo‐controlled, parallel‐group study of both memantine and constraint‐induced aphasia therapy (CIAT) on chronic poststroke aphasia followed by an open‐label extension phase.
Methods
Patients were randomized to memantine (20mg/day) or placebo alone during 16 weeks, followed by combined drug treatment with CIAT (weeks 16–18), drug treatment alone (weeks 18–20), and washout (weeks 20–24), and finally, an open‐label extension phase of memantine (weeks 24–48). After baseline evaluations, clinical assessments were done at two end points (weeks 16 and 18), and at weeks 20, 24, and 48. Outcome measures were changes in the Western Aphasia Battery‐Aphasia Quotient and the Communicative Activity Log.
Results
Twenty‐eight patients were included, and 27 completed both treatment phases. The memantine group showed significantly better improvement on Western Aphasia Battery‐Aphasia Quotient compared with the placebo group while the drug was taken (week 16, p = 0.002; week 18, p = 0.0001; week 20, p = 0.005) and at the washout assessment (p = 0.041). A significant increase in Communicative Activity Log was found in favor of memantine‐CIAT relative to placebo‐CIAT (week 18, p = 0.040). CIAT treatment led to significant improvement in both groups (p = 0.001), which was even greater under additional memantine treatment (p = 0.038). Beneficial effects of memantine were maintained in the long‐term follow‐up evaluation, and patients who switched to memantine from placebo experienced a benefit (p = 0.02).
Interpretation
Both memantine and CIAT alone improved aphasia severity, but best outcomes were achieved combining memantine with CIAT. Beneficial effects of memantine and CIAT persisted on long‐term follow‐up. Ann Neurol 2009;65:577–585
Angiogenesis is increased in B-cell chronic lymphocytic leukemia (B-CLL). We wanted to quantify and characterize the circulating endothelial cells (CECs) in patients with B-CLL and correlate with plasma angiogenesis-related factors. Using a four-color flow cytometry, we prospectively analyzed the CEC in the whole blood of 20 healthy controls and 20 patients with B-CLL. We quantified (CD45-/CD31+/CD146+) and characterized the CECs according to whether they were apoptotic (annexin stain) or activated (CD106+). We also measured plasma levels of vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), and thrombospondin-1 (TSP-1). Most patients (90%) had Rai stages 0-2 at the time of diagnosis. As a group, B-CLL patients had higher number of CECs (median of 26.5 cells/ml) compared (P = 0.04) to healthy controls (18.5 cells/ml). However, only four (20%) patients had elevated CEC counts, defined as >/=2 SD of the control mean (>/=53 cells/ml). The proportions of apoptotic (P = 0.83) and activated (P = 0.12) CECs were similar in both groups. B-CLL patients had higher FGF-2 (P < 0.001), lower TSP-1 (P = 0.004), and similar VEGF (P = 0.27) plasma levels. The number of CECs was not associated with Rai stage, absolute lymphocyte count, or levels of angiogenesis-related factors. CECs are increased in only a small fraction of B-CLL patients in our cohort with low rates of apoptosis and activation. While no correlation was found between CECs and clinical features, more studies in a larger patient sample size and advanced disease are necessary.
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