Randomized assessment of imatinib in patients with acute ischaemic stroke treated with intravenous thrombolysis.

BACKGROUND: Imatinib, a tyrosine kinase inhibitor, has been shown to restore blood-brain barrier integrity and reduce infarct size, haemorrhagic transformation and cerebral oedema in stroke models treated with tissue plasminogen activator. We evaluated the safety of imatinib, based on clinical and neuroradiological data, and its potential influence on neurological and functional outcomes. METHODS: A phase II randomized trial was performed in patients with acute ischaemic stroke treated with intravenous thrombolysis. A total of 60 patients were randomly assigned to four groups [3 (active): 1 (control)]; the active treatment groups received oral imatinib for 6 days at three dose levels (400, 600 and 800 mg). Primary outcome was any adverse event; secondary outcomes were haemorrhagic transformation, cerebral oedema, neurological severity on the National Institutes of Health Stroke Scale (NIHSS) at 7 days and at 3 months and functional outcomes on the modified Rankin scale (mRS). RESULTS: Four serious adverse events were reported, which resulted in three deaths (one in the control group and two in the 400-mg dose group; one patient in the latter group did not receive active treatment and the other received two doses). Nonserious adverse events were mostly mild, resulting in full recovery. Imatinib ameliorated neurological outcomes with an improvement of 0.6 NIHSS points per 100 mg imatinib (P = 0.02). For the 800-mg group, the mean unadjusted and adjusted NIHSS improvements were 4 (P = 0.037) and 5 points (P = 0.012), respectively, versus controls. Functional independence (mRS 0-2) increased by 18% versus controls (61 vs. 79; P = 0.296). CONCLUSION: This phase II study showed that imatinib is safe and tolerable and may reduce neurological disability in patients treated with intravenous thrombolysis after ischaemic stroke. A confirmatory randomized trial is currently underway.

A randomized controlled trial on very early speech and language therapy in acute stroke patients with aphasia.

BACKGROUND: Aphasia affects one third of acute stroke patients. There is a considerable spontaneous recovery in aphasia, but impaired communication ability remains a great problem. Communication difficulties are an impediment to rehabilitation. Early treatment of the language deficits leading to increased communication ability would improve rehabilitation. The aim of this study is to elucidate the efficacy of very early speech and language therapy (SLT) in acute stroke patients with aphasia. METHODS: A prospective, open, randomized, controlled trial was carried out with blinded endpoint evaluation of SLT, starting within 2 days of stroke onset and lasting for 21 days. 123 consecutive patients with acute, first-ever ischemic stroke and aphasia were randomized. The SLT treatment was Language Enrichment Therapy, and the aphasia tests used were the Norsk grunntest for afasi (NGA) and the Amsterdam-Nijmegen everyday language test (ANELT), both performed by speech pathologists, blinded for randomization. RESULTS: The primary outcome, as measured by ANELT at day 21, was 1.3 in the actively treated patient group and 1.2 among controls. NGA led to similar results in both groups. Patients with a higher level of education (>12 years) improved more on ANELT by day 21 than those with <12 years of education (3.4 vs. 1.0, respectively). In 34 patients in the treatment group and 19 in the control group improvement was ≥1 on ANELT (p < 0.05). There was no difference in the degree of aphasia at baseline except for fluency, which was higher in the group responding to treatment. CONCLUSIONS: Very early intensive SLT with the Language Enrichment Therapy program over 21 days had no effect on the degree of aphasia in unselected acute aphasic stroke patients. In aphasic patients with more fluency, SLT resulted in a significant improvement as compared to controls. A higher educational level of >12 years was beneficial.

Design and methods of a randomized controlled trial on early speech and language therapy in patients with acute stroke and aphasia.

PURPOSE: Most clinicians would recommend speech and language therapy (SLT) for aphasic patients. The question of when and for how long SLT should be administered still remains controversial. The aim of this trial is to evaluate the efficacy of early SLT in patients with acute stroke and aphasia in a randomized controlled trial. This report will present design and methods and discuss feasibility. METHOD: Consecutive patients with first ever ischemic stroke and aphasia are assessed by the Amsterdam-Nijmegen Everyday Language Test (ANELT) and a short version of the Norsk Grunntest for Afasi. The treatment is language enrichment therapy, and the therapy is given 45 min/day for 15 weekdays. The primary outcome is the difference in the degree of aphasia between the SLT treated group and the control group measured by ANELT at 3 weeks. RESULTS: Around 10% of acute consecutive patients with aphasia are included. Of the first 79 included patients, 86% have completed the study according to protocol. We intend to include 125 patients, which provide sufficient statistical power to detect a clinically significant difference in the degree of aphasia. CONCLUSION: It is feasible to conduct a randomized controlled study on very early SLT for acute aphasic patients.

Recognition of depression in aphasic stroke patients.

BACKGROUND: Data on post-stroke depression in aphasia are scarce. METHODS: Eighty-nine acute stroke patients with aphasia of all types were followed for 6 months to investigate if depression can be reliably diagnosed (DSM-IV criteria) and validly assessed by the verbal Montgomery-Asberg Depression Rating Scale (MADRS) and a global technique (Clinical Global Impressions Rating Scale for Severity). A standard aphasia test was performed. RESULTS: In 60 patients (67%) at baseline and in 100% at 6 months, comprehension allowed a reliable DSM-IV diagnosis. Among these patients MADRS was feasible in 95% at baseline and in 100% at 6 months. The assistance of relatives and staff increases the feasibility and decreases the validity. Depression was identified in 24% during the 6 months. CONCLUSION: Depression diagnosis and severity rating can reliably be made in the acute phase in at least two thirds of aphasic patients, and feasibility increases over time.

Long-term antidepressant treatment with moclobemide for aphasia in acute stroke patients: a randomised, double-blind, placebo-controlled study.

BACKGROUND AND PURPOSE: Pharmacotherapy aimed at stroke rehabilitation through direct central nervous effects may be assumed to work in a similar way for language recovery and sensory-motor recovery. Some data suggest that antidepressant drugs could be beneficial also for functional improvement. This prompted us to investigate whether regression from aphasia after acute stroke could be enhanced by antidepressive drug therapy. METHODS: We randomised 90 acute stroke patients with aphasia to either 600 mg moclobemide or placebo daily for 6 months, within 3 weeks of the onset of stroke. Aphasia was assessed prior to treatment and at 6 months, using Reinvang's 'Grunntest for afasi' and the Amsterdam-Nijmegen-Everyday-Language-Test (ANELT). RESULT: The degree of aphasia decreased significantly at 6 months, with no difference between the moclobemide- and the placebo-treated groups. Multivariate regression analysis including treatment group, activities of daily living, aetiology of stroke, ANELT, and Reinvang's coefficient at baseline, and neurological deficit confirmed these results. In all, 13 in the moclobemide and 10 in the placebo group stopped taking the study medication. No further change was found in the 56 aphasic patients followed up for another 6 months with no medication. CONCLUSIONS: Compared to placebo, treatment with moclobemide for 6 months did not enhance the regression of aphasia following an acute stroke.

Aphasia in acute stroke and relation to outcome.

OBJECTIVES: The natural course of aphasia in unselected, consecutive stroke patients is not well established. We investigated morbidity, mortality and recovery for different types of aphasia in consecutive unselected aphasic patients with acute stroke. Setting and subjects. In 119 aphasic patients, the type and degree of aphasia were assessed acutely and at 3, 6 and 18 months after stroke onset, using Reinvang's 'Grunntest for afasi' and Amsterdam-Nijmegen-Everyday-Language-Test. RESULTS: About one-third of patients with acute stroke had presented with aphasia. Mortality among the aphasic patients during the 18-month follow-up was twice that in non-aphasics (36 vs. 16%). Presence of atrial fibrillation was associated with poorer prognosis. At 18 months, 24% of the 119 aphasic patients had recovered completely, 43% still had significant aphasia, and 21% had died. The proportion with global aphasia decreased from almost 25% acutely to a few per cent after 18 months, that with Wernicke's aphasia from 25% to less than 10%, whereas conduction aphasia increased from 13 to 23% during follow-up. Among those with initial mild aphasia, 70% recovered completely. Great improvement was observed in patients with initial low degree of speech function. Younger patients recovered to a greater extent than older patients. CONCLUSION: The high long-term mortality among aphasics may be seen as an indirect sign of advanced cardiovascular disease. A combination of different and adjusted aphasia tests provided the possibility to assess almost all acute aphasic patients. Irrespective of type and degree of aphasia, great improvements were seen in almost all aphasic patients. Even patients with severe speech impairment have a considerable potential for recovery, particularly in the first 3 months after stroke.