ABSTRACT
BACKGROUND AND PURPOSE: Numerous preclinical findings and a clinical pilot study suggest that recombinant human erythropoietin (EPO) provides neuroprotection that may be beneficial for the treatment of patients with ischemic stroke. Although EPO has been considered to be a safe and well-tolerated drug over 2 decades, recent studies have identified increased thromboembolic complications and/or mortality risks on EPO administration to patients with cancer or chronic kidney disease. Accordingly, the double-blind, placebo-controlled, randomized German Multicenter EPO Stroke Trial (Phase II/III; ClinicalTrials.gov Identifier: NCT00604630) was designed to evaluate efficacy and safety of EPO in stroke. METHODS: This clinical trial enrolled 522 patients with acute ischemic stroke in the middle cerebral artery territory (intent-to-treat population) with 460 patients treated as planned (per-protocol population). Within 6 hours of symptom onset, at 24 and 48 hours, EPO was infused intravenously (40,000 IU each). Systemic thrombolysis with recombinant tissue plasminogen activator was allowed and stratified for. RESULTS: Unexpectedly, a very high number of patients received recombinant tissue plasminogen activator (63.4%). On analysis of total intent-to-treat and per-protocol populations, neither primary outcome Barthel Index on Day 90 (P=0.45) nor any of the other outcome parameters showed favorable effects of EPO. There was an overall death rate of 16.4% (n=42 of 256) in the EPO and 9.0% (n=24 of 266) in the placebo group (OR, 1.98; 95% CI, 1.16 to 3.38; P=0.01) without any particular mechanism of death unexpected after stroke. CONCLUSIONS: Based on analysis of total intent-to-treat and per-protocol populations only, this is a negative trial that also raises safety concerns, particularly in patients receiving systemic thrombolysis.
Subject(s)
Brain Ischemia/drug therapy , Erythropoietin/administration & dosage , Erythropoietin/adverse effects , Neuroprotective Agents/administration & dosage , Neuroprotective Agents/adverse effects , Stroke/drug therapy , Acute Disease/therapy , Adult , Aged , Aged, 80 and over , Brain Ischemia/physiopathology , Double-Blind Method , Drug Administration Schedule , Drug Interactions/physiology , Drug-Related Side Effects and Adverse Reactions , Female , Humans , Infarction, Middle Cerebral Artery/drug therapy , Infarction, Middle Cerebral Artery/physiopathology , Injections, Intravenous , Male , Middle Aged , Mortality , Patient Selection , Placebo Effect , Recombinant Proteins/administration & dosage , Stroke/physiopathology , Tissue Plasminogen Activator/administration & dosage , Tissue Plasminogen Activator/adverse effects , Treatment Outcome , Young AdultABSTRACT
PURPOSE: Cognitive disorders are common in MS patients without any generally recommended treatment. Recent brain imaging studies show considerable neuroplasticity for cognitive tasks in MS patients, but also brain atrophy already early in the disease progression. We explored the benefits of a home-based cognitive training program for memory and working memory functions in relapsing-remitting MS patients controlling for whole brain and central brain atrophy as covariates. METHODS: Using a single-blinded controlled study design, 42 patients were randomised into a treatment group and a control group. Home based computer training focusing on memory and working memory was started at least 4 weeks after the discontinuation of methylprednisolone treatment and lasted for 6 weeks. Two weeks later the patients were re-investigated for their clinical and cognitive performance. We assessed also quality of life (QoL), depression and fatigue using self-rating scales. RESULTS: Training had no effect on the neurological status and on QoL or fatigue. However, the treatment group showed better verbal learning, long-delay verbal memory performance, and working memory performance. The impact of treatment on long-delay verbal memory performance was independent from the extent of brain atrophy, whereas for the other findings brain atrophy played a significant role. CONCLUSIONS: An intensive home-based cognitive training program is suitable to improve the cognitive performance of MS patients. The impact of brain atrophy on rehabilitation outcome may differ for cognitive functions.
Subject(s)
Brain/pathology , Cognitive Behavioral Therapy/methods , Multiple Sclerosis, Relapsing-Remitting/complications , Multiple Sclerosis, Relapsing-Remitting/rehabilitation , Adult , Analysis of Variance , Atrophy/rehabilitation , Cognition/physiology , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Multiple Sclerosis , Multiple Sclerosis, Relapsing-Remitting/psychology , Neuropsychological Tests , Quality of Life , Severity of Illness Index , Single-Blind MethodABSTRACT
OBJECTIVE: To compare the neuropsychological deficits of primary progressive multiple sclerosis with those of relapsing-remitting and secondary progressive multiple sclerosis. METHODS: Sixty-five patients with different clinical courses of MS were neuropsychologically tested for language, attention, memory and executive functions. Discriminant analysis was used to predict the type of clinical course either by clinical variables (age, EDSS and duration of illness) or neuropsychological test results. RESULTS: For single neuropsychological tests, group differences were rare between the progressive courses and the relapsing-remitting course of MS or absent between the progressive courses of MS. However, discriminant analysis correctly identified 87.7 percent of the patients' courses in general, and about 90 percent of the patients with chronic progressive MS. CONCLUSION: Using discriminant analysis, this study found neuropsychological impairment characteristic for relapsing remitting, secondary progressive and primary progressive patients.
