Ann Charlotte Laska

Aphasia in acute stroke and relation to outcome

Abstract. Laska AC, Hellblom A, Murray V, Kahan T, von Arbin M (Danderyd Hospital, Danderyd, Sweden). Aphasia in acute stroke and relation to outcome. J Intern Med 2001; 249: 413–422.

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.

NETosis promotes cancer-associated arterial microthrombosis presenting as ischemic stroke with troponin elevation.

INTRODUCTION Large elevations of high sensitive Troponin T (hsTnT) in ischemic stroke patients is associated with a poor outcome. In a pilot study we found a high prevalence of malignancies among these patients. Since neutrophil extracellular traps (NETs) have been linked to cancer-associated thrombosis, we hypothesized that the concomitant cerebral and myocardial ischemia could be the result of a NET-induced hypercoagulable state. MATERIALS AND METHODS Clinical assessments, plasma analyses and autopsies with histopathology (in cases of in-hospital mortality) were performed on ischemic stroke patients with high elevations of hsTnT (N=12) and normal hsTnT (N=19). RESULTS Patients with hsTnT elevation had an unexpectedly higher prevalence of cancer (p=0.002), half of which were diagnosed post-mortem. Autopsies of these patients revealed widespread myocardial, cerebral and pulmonary microthrombosis with H3Cit in thrombi. A pro-coagulant state and an increase of the NET specific marker citrullinated histone H3 (H3Cit) was found in plasma of patients with elevated hsTnT compared to patients with normal levels (p<0.001). Plasma analyses in cancer patients showed even higher H3Cit levels (p<0.001), and an increase in granulocyte colony-stimulating factor, known to prime neutrophils towards NETosis. H3Cit correlated positively with thrombin-antithrombin complex (p=0.004) and soluble P-selectin (p<0.001), further linking NETosis to the pro-thrombotic state. CONCLUSIONS The high prevalence of known or occult cancer in our study suggests that cancer-associated arterial microthrombosis may be underestimated. By linking the thrombosis to NETs, we suggest markers of NETosis that could aid in revealing cancer in arterial microthrombosis as well as arterial microthrombosis in cancer.

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-Åsberg 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.

Clinical and prognostic properties of standardized and functional aphasia assessments.

OBJECTIVE To compare standardized and functional aphasia tests in patients after acute stroke. DESIGN Data were collected at baseline and at 6 months in 2 prospective single-centre studies: one observational study (study I, n=119) and one randomized trial of moclobemide vs placebo (study II, n=89). SUBJECTS Patients with aphasia after acute stroke. METHODS Degree of aphasia was examined using the Coefficient (Coeff) in Norsk Grunntest for Afasi (standardized) and the Amsterdam-Nijmegen Everyday Language Test (ANELT) (functional). Statistical comparisons were made using one-way analysis of variance and multivariate regression analyses. RESULTS The degree of aphasia measured with Coeff and ANELT correlated closely throughout the study (r2=0.71-0.87, p<0.0001). In study I, 24 patients recovered completely within 6 months. A Coeff >or= 49 and ANELT >or= 3.5 predicted complete recovery equally well. Coeff was sensitive to differentiate between patients with low values on ANELT, whereas ANELT was sensitive to differentiate between patients with high Coeff values. CONCLUSION The 2 tests show a close and consistent correlation over time and are equally sensitive to improvement. They have a similar capacity to predict complete recovery. A standardized test appears to be more suitable for patients with aphasia in the acute stage, while a functional test is more suitable in the subacute/chronic stage.

Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2): an international randomised, placebo-controlled, phase 3 superiority trial

Summary Background Tranexamic acid can prevent death due to bleeding after trauma and post-partum haemorrhage. We aimed to assess whether tranexamic acid reduces haematoma expansion and improves outcome in adults with stroke due to intracerebral haemorrhage. Methods We did an international, randomised placebo-controlled trial in adults with intracerebral haemorrhage from acute stroke units at 124 hospital sites in 12 countries. Participants were randomly assigned (1:1) to receive 1 g intravenous tranexamic acid bolus followed by an 8 h infusion of 1 g tranexamic acid or a matching placebo, within 8 h of symptom onset. Randomisation was done centrally in real time via a secure website, with stratification by country and minimisation on key prognostic factors. Treatment allocation was concealed from patients, outcome assessors, and all other health-care workers involved in the trial. The primary outcome was functional status at day 90, measured by shift in the modified Rankin Scale, using ordinal logistic regression with adjustment for stratification and minimisation criteria. All analyses were done on an intention-to-treat basis. This trial is registered with the ISRCTN registry, number ISRCTN93732214. Findings We recruited 2325 participants between March 1, 2013, and Sept 30, 2017. 1161 patients received tranexamic acid and 1164 received placebo; the treatment groups were well balanced at baseline. The primary outcome was assessed for 2307 (99%) participants. The primary outcome, functional status at day 90, did not differ significantly between the groups (adjusted odds ratio [aOR] 0·88, 95% CI 0·76–1·03, p=0·11). Although there were fewer deaths by day 7 in the tranexamic acid group (101 [9%] deaths in the tranexamic acid group vs 123 [11%] deaths in the placebo group; aOR 0·73, 0·53–0·99, p=0·0406), there was no difference in case fatality at 90 days (250 [22%] vs 249 [21%]; adjusted hazard ratio 0·92, 95% CI 0·77–1·10, p=0·37). Fewer patients had serious adverse events after tranexamic acid than after placebo by days 2 (379 [33%] patients vs 417 [36%] patients), 7 (456 [39%] vs 497 [43%]), and 90 (521 [45%] vs 556 [48%]). Interpretation Functional status 90 days after intracerebral haemorrhage did not differ significantly between patients who received tranexamic acid and those who received placebo, despite a reduction in early deaths and serious adverse events. Larger randomised trials are needed to confirm or refute a clinically significant treatment effect. Funding National Institute of Health Research Health Technology Assessment Programme and Swiss Heart Foundation.

Clopidogrel Resistance after Minor Ischemic Stroke or Transient Ischemic Attack is Associated with Radiological Cerebral Small-Vessel Disease.

BACKGROUND The objective of this study was to compare nonresponders (NR) and responders (R) to clopidogrel with respect to presence of microvascular and macrovascular pathology in a cohort of patients with recent minor ischemic stroke (IS) or transient ischemic attack (TIA). METHODS Seventy-two patients treated with clopidogrel after IS or TIA were evaluated 1 month after onset. Platelet aggregation was measured by multiple electrode aggregometry (Multiplate). Nonresponse was defined according to recent consensus. The degree of cerebral small-vessel disease (cSVD) was evaluated on computed tomography scans of the brain using Fazekas scale for white matter changes. Carotid atherosclerosis was evaluated by ultrasound or computed tomography/magnetic resonance angiography. RESULTS Twenty-two percent of patients were NR. Moderate to extensive cSVD was more common for NR than R, 56% versus 25%, odds ratio 3.9 (1.2-12), P = .03. Correspondingly, 39% of patients with cSVD were NR versus 14% of patients with no or mild cSVD. No differences were found between NR and R in prevalence or severity of carotid atherosclerosis. NR had higher platelet aggregation response than R after stimulation with arachidonic acid or thrombin receptor-activating peptide, indicating a general platelet hyperreactivity. In a univariate analysis, hypertension, previous IS, glucose intolerance, pulse pressure above median, and presence of moderate to extensive cSVD were associated with the NR phenotype. CONCLUSIONS Nonresponsiveness to clopidogrel after minor IS or TIA is associated with radiological cSVD but not with carotid atherosclerosis. PRACTICE/IMPLICATIONS Measurement of platelet function is warranted in patients with cSVD. Larger studies on alternative or tailored antiplatelet treatment for these patients should be initiated.

Elevated Troponin Levels in Acute Stroke Patients Predict Long-term Mortality

BACKGROUND Elevated plasma levels of troponin in acute stroke patients are common and have in several studies been shown to predict in-hospital and short-term mortality. Little is, however, known about the long-term prognosis of these patients. The aim of this study was to determine patient characteristics and 5-year mortality in patients with acute stroke and troponin elevation on admission. METHODS A retrospective cohort study of all consecutive patients with acute stroke and a plasma troponin I (TnI) analyzed on admission to Danderyd Hospital between January 1, 2005, and January 1, 2006 (n = 247). Patient characteristics were obtained from the Swedish National Stroke Register, Riksstroke, as well as hospital records. Mortality data were obtained from the Swedish Cause of Death Register. RESULTS There were 133 patients (54%) with TnI less than .03 μg/L (normal), 74 patients (30%) with TnI .03-.11 μg/L (low elevation), and 40 patients (16%) with TnI greater than .11 μg/L (high elevation). TnI elevations were associated with a higher age, prior ischemic stroke, chronic heart failure, renal insufficiency, stroke severity, and ST segment elevation or depression on admission. The rate of hyperlipidemia decreased with increasing TnI. Adjusted for age and comorbidity, elevated TnI values on admission had a significantly and sustained increased mortality over the 5-year follow-up, with a hazard ratio of 1.90 (95% confidence interval, 1.33-2.70). CONCLUSIONS Troponin elevation in patients with acute stroke, even when adjusted for several possible confounders, is associated with an almost 2-fold increased risk of 5-year mortality.

Trousseau’s Syndrome, a Previously Unrecognized Condition in Acute Ischemic Stroke Associated With Myocardial Injury

Trousseau’s syndrome is a well-known malignancy associated hypercoagulative state leading to venous or arterial thrombosis. The pathophysiology is however poorly understood, although multiple mechanisms are believed to be involved. We report a case of Trousseau’s syndrome resulting in concomitant cerebral and myocardial microthrombosis, presenting with acute ischemic stroke and markedly elevated plasma troponin T levels suggesting myocardial injury. Without any previous medical history, the patient developed multiple cerebral infarctions and died within 11 days of admission. The patient was postmortem diagnosed with an advanced metastatic adenocarcinoma of the prostate with disseminated cerebral, pulmonary, and myocardial microthrombosis. Further analyses revealed, to the best of our knowledge for the first time in stroke patients, circulating microvesicles positive for the epithelial tumor marker CK18 and citrullinated histone H3 in thrombi, markers of the recently described cancer-associated procoagulant DNA-based neutrophil extracellular traps. We also found tissue factor, the main in vivo initiator of coagulation, both in thrombi and in metastases. Troponin elevation in acute ischemic stroke is common and has repeatedly been associated with an increased risk of mortality. The underlying pathophysiology is however not fully clarified, although a number of possible explanations have been proposed. We now suggest that unexplainable high levels of troponin in acute ischemic stroke deserve special attention in terms of possible occult malignancy.

Patients with aphasia and an infarct in Wernicke’s area benefit from early intensive speech and language therapy

ABSTRACT Background: Considerable spontaneous recovery is observed in aphasia, but impaired communication ability remains a great problem. Almost half of the patients still have aphasia one year after stroke onset, but usually in a milder form. Aim: The aim of this study was to assess the effect of very early intensive speech and language therapy (SLT) and correlate it with the location of the cerebral infarction in acute ischemic stroke patients with aphasia. Methods & Procedures: In this randomised study, 118 patients with acute cerebral infarction and aphasia were included and assigned either for three weeks of intensive SLT or part of the control group. The patients were evaluated by a speech therapist regarding aphasia with two language tests, Norsk Grunntest for Afasi and Amsterdam–Nijmegen Everyday Language Test in the acute phase, after three weeks and after six months. All patients were radiologically examined in the acute phase and after three weeks. Outcomes & Results: A total of 14 of 18 (78%) speech and language trained patients with infarction involving Wernicke’s and central areas, but with intact Broca’s area showed significant improvements of aphasia compared to 4 of 16 (25%) in the control group (p < 0.01). Patients with no visible radiological infarct had less severe initial language impairment and all of them in the training group showed significant improvements of aphasia. Conclusions: Patients with radiologically proven cerebral infarct involving Wernicke’s area with or without infarctions centrally can benefit from early intensive SLT.