Speech therapy after stroke: trial shows only that practice varies

Bowen and colleagues’ methods and conclusions raise concerns.1 At best, the trial evaluates the variability in current practice. In no way is it a robust test of treatment. Two communication impairments (aphasia and dysarthria) were included. In the post-acute stage spontaneous recovery is highly unpredictable, and changes in the profile of impairment during this time are common.2 Both impairments manifest in different forms,3 which may be more or less responsive to treatment. A third kind of impairment, apraxia of speech, was not excluded but was not targeted in therapy. All three impairments can and do co-occur. Whether randomised controlled trial designs can effectively cope with such complex disorders has been discussed elsewhere.4 Treatment was defined within terms of current practice but was unconstrained. Therefore, the treatment group would have received a variety of therapeutic approaches and protocols, some of which may indeed be ineffective. Only 53% of the contact time with a speech and language therapist was direct (one to one), the rest was impairment based therapy. In contrast, all of the visitors’ time was direct contact, usually in conversation. In both groups, the frequency and length of contact time varied. We already know that the transfer from impairment based therapy to functional communication can be limited and varies across individuals.5 However, it is not possible to conclude from this trial that one to one impairment based therapy should be replaced. For that, a well defined impairment therapy protocol must be directly compared with a similarly well defined functional communication therapy, with an attention control.

Are anatomic brain locations important in determining the clinical outcomes in acute ischemic stroke? --- An exploratory analysis of the NINDS Stroke Trial data

Background and purpose. Brain lesions in acute ischemic stroke measured by imaging tools provide important clinical information for diagnosis and final infarct volume has been considered as a potential surrogate marker for clinical outcomes. Strong correlations have been found between lesion volume and clinical outcomes in the NINDS t-PA Stroke Trial but little has been published about lesion location and clinical outcomes. Studies of the National Institute of Neurological Disorders and Stroke (NINDS) t-PA Stroke Trial data found the direction of the t-PA treatment effect on a decrease in CT lesion volume was consistent with the observed clinical effects at 3 months, but measure of t-PA treatment benefits using CT lesion volumes showed a diminished statistical significance, as compared to using clinical scales. ^ Methods. We used the global test to evaluate the hypothesis that lesion locations were strongly associated with clinical outcomes within each treatment group at 3 months after stroke. The anatomic locations of CT scans were used for analysis. We also assessed the effect of t-PA on lesion location using a global statistical test. ^ Results. In the t-PA group, patients with frontal lesions had larger infarct volumes and worse NIHSS score at 3 months after stroke. The clinical status of patients with frontal lesions in t-PA group was less likely to be affected by lesion volume, as compared to those who had no frontal lesions in at 3 months. For patients within the placebo group, both brain stem and internal capsule locations were significantly associated with a lower odd of having favorable outcomes at 3 months. Using a global test we could not detect a significant effect of t-PA treatment on lesion location although differences between two treatment groups in the proportion of lesion findings in each location were found. ^ Conclusions. Frontal, brain stem, and internal capsule locations were significantly related to clinical status at 3 months after stroke onset. We detect no significant t-PA effect on all 9 locations although proportion of lesion findings in differed among locations between the two treatment groups.^

Sex differences in quality of life in stroke survivors. Data from the Tinzaparin in Acute Ischaemic Stroke Trial (TAIST)

Introduction: Female sex is predictive of poor functional outcome in stroke, even after correction for prognostic factors. Poor quality of life (QoL) is observed in stroke survivors, with lower scores seen in the most disabled patients. We used data from the TAIST trial to assess the relationship between sex and QoL after ischaemic stroke. Methods: TAIST was a randomised controlled trial assessing the safety and efficacy of tinzaparin versus aspirin in 1,484 patients with acute ischaemic stroke. QoL was measured at 180 days post randomisation using the short-form 36 health survey which assesses QoL across eight domains. The relationship between sex and each domain was assessed using ordinal regression, both unadjusted and adjusted for key prognostics factors. Results: Of the 1,484 patients randomised into TAIST, 216 had died at 180 days post randomisation. 1,268 survivors were included in this analysis, 694 males (55%), 574 females (45%). Females tended to score lower than males across all QoL domains (apart from general health); statistically significant lower scores were seen for physical functioning (odds ratio (OR) 0.58, 95% confidence interval (CI) 0.47-0.72), vitality (OR 0.79, 95% CI 0.64-0.98) and mental health (OR 0.75, 95% CI 0.61-0.93). The results for physical functioning and mental health remained significant after adjustment for prognostic variables (OR 0.73, 95% CI 0.58-0.92; OR 0.76, 95% CI 0.60-0.95 respectively). Conclusions: QoL, in particular physical function and mental health domains, is lower in female patients after stroke. This difference persists even after correction for known prognostic factors such as age and stroke severity.

Stroke severity, early recovery and outcome are each related with clinical classification of stroke: data from the 'Tinzaparin in Acute Ischaemic Stroke Trial (TAIST)

Introduction: Baseline severity and clinical stroke syndrome (Oxford Community Stroke Project, OCSP) classification are predictors of outcome in stroke. We used data from the ‘Tinzaparin in Acute Ischaemic Stroke Trial’ (TAIST) to assess the relationship between stroke severity, early recovery, outcome and OCSP syndrome. Methods: TAIST was a randomised controlled trial assessing the safety and efficacy of tinzaparin versus aspirin in 1,484 patients with acute ischaemic stroke. Severity was measured as the Scandinavian Neurological Stroke Scale (SNSS) at baseline and days 4, 7 and 10, and baseline OCSP clinical classification recorded: total anterior circulation infarct (TACI), partial anterior circulation infarct (PACI), lacunar infarct (LACI) and posterior circulation infarction (POCI). Recovery was calculated as change in SNSS from baseline at day 4 and 10. The relationship between stroke syndrome and SNSS at days 4 and 10, and outcome (modified Rankin scale at 90 days) were assessed. Results: Stroke severity was significantly different between TACI (most severe) and LACI (mildest) at all four time points (p<0.001), with no difference between PACI and POCI. The largest change in SNSS score occurred between baseline and day 4; improvement was least in TACI (median 2 units), compared to other groups (median 3 units) (p<0.001). If SNSS did not improve by day 4, then early recovery and late functional outcome tended to be limited irrespective of clinical syndrome (SNSS, baseline: 31, day 10: 32; mRS, day 90: 4); patients who recovered early tended to continue to improve and had better functional outcome irrespective of syndrome (SNSS, baseline: 35, day 10: 50; mRS, day 90: 2). Conclusions: Although functional outcome is related to baseline clinical syndrome (best with LACI, worst with TACI), patients who improve early have a more favourable functional outcome, irrespective of their OCSP syndrome. Hence, patients with a TACI syndrome may still achieve a reasonable outcome if early recovery occurs.

Compression stockings and the prevention of symptomatic venous thromboembolism: data from the Tinzaparin in Acute Ischaemic Stroke Trial

Background: Venous thromboembolism (VTE) is a well recognised and preventable complication of acute stroke. While graduated compression stockings reduce the risk of VTE in surgical patients their benefit in acute stroke remains uncertain. Methods: The relationship between symptomatic VTE and use of stockings using observational data from the ‘Tinzaparin in Acute Ischaemic Stroke Trial’, which compared 10 days of treatment with tinzaparin (175 IU.kg-1 or 100 IU.kg-1) with, aspirin (300 mg od), was assessed using logistic regression adjusted for known VTE risk factors and treatment. Results: Symptomatic VTE occurred in 28 patients (1.9%, DVT 18, PE 13) within 15 days of enrolment in 1,479 patients. Patients wearing one or two stockings for any period of time during the first 10 days (n=803) had a non-significant increase (odds ratio, OR 2.45, 95% confidence interval, CI 0.95 - 6.32) in the risk of symptomatic VTE. In contrast, those wearing bilateral stockings for 10 days (n=374) had a non-significant reduction in the odds of symptomatic VTE as compared to those who wore no stockings or wore them for less than 10 days (OR 0.65, 95% CI 0.26-1.65). Mild stroke and treatment with tinzaparin were associated with a reduced risk of VTE. Conclusions: Bilateral graduated compression stockings may reduce the incidence of VTE by one-third in patients with acute ischaemic stroke. However, the uncertainty in this finding, low frequency of symptomatic VTE, potential for stockings to cause harm, and cost of stockings highlight the need for a large randomised-controlled trial to examine the safety and efficacy of stockings in acute stroke.

The relationship between baseline blood pressure and computed tomography findings in acute stroke: data from the Tinzaparin in Acute Ischaemic Stroke Trial (TAIST)

Background and Purpose—High blood pressure (BP) is present in 80% of patients with acute ischemic stroke and is independently associated with poor outcome. There are few data examining the relationship between admission BP and acute CT findings. Methods—TAIST was a randomized controlled trial assessing 10 days of treatment with tinzaparin versus aspirin in 1489 patients with acute ischemic stroke (48 hr) with admission BP of 220/120 mm Hg. CT brain scans were performed before randomization and after 10 days. The relationships between baseline BP and adjudicated CT findings were assessed. Odds ratios per 10 mm Hg change in BP were calculated. Results—Higher systolic BP (SBP) was associated with abnormal CT scans because of independent associations with chronic changes of leukoariosis (OR, 1.12; 95% CI, 1.05–1.17) and old infarction (OR, 1.12; 95% CI, 1.06 –1.17) at baseline, and signs of visible infarction at day 10 (OR, 1.06; 95% CI, 1.00 –1.13). A lower SBP was associated with signs of acute infarction (OR, 0.94; 95% CI, 0.89–0.99). Hemorrhagic transformation, dense middle cerebral artery sign, mass effect, and cerebral edema at day 10 were not independently associated with baseline BP. Conclusion—Although high baseline BP is independently associated with a poor outcome after stroke, this was not shown to be through an association with increased hemorrhagic transformation, cerebral edema, or mass effect; trial design may be suboptimal to detect this. Higher SBP is associated with visible infarction on day 10 scans. The influence of changing BP in acute stroke on CT findings is still to be ascertained.

Evaluation of a sequential global test of improved recovery following stroke as applied to the ICTUS trial of citicoline

The International Citicoline Trial in acUte Stroke is a sequential phase III study of the use of the drug citicoline in the treatment of acute ischaemic stroke, which was initiated in 2006 in 56 treatment centres. The primary objective of the trial is to demonstrate improved recovery of patients randomized to citicoline relative to those randomized to placebo after 12 weeks of follow-up. The primary analysis will take the form of a global test combining the dichotomized results of assessments on three well-established scales: the Barthel Index, the modified Rankin scale and the National Institutes of Health Stroke Scale. This approach was previously used in the analysis of the influential National Institute of Neurological Disorders and Stroke trial of recombinant tissue plasminogen activator in stroke. The purpose of this paper is to describe how this trial was designed, and in particular how the simultaneous objectives of taking into account three assessment scales, performing a series of interim analyses and conducting treatment allocation and adjusting the analyses to account for prognostic factors, including more than 50 treatment centres, were addressed. Copyright (C) 2008 John Wiley & Sons, Ltd.

Feasibility platform for stroke studies: an online tool to improve eligibility criteria for clinical trials

BACKGROUND AND PURPOSE Eligibility criteria are a key factor for the feasibility and validity of clinical trials. We aimed to develop an online tool to assess the potential effect of inclusion and exclusion criteria on the proportion of patients eligible for an acute stroke trial. METHODS We identified relevant inclusion and exclusion criteria of acute stroke trials. Based on these criteria and using a cohort of 1537 consecutive patients with acute ischemic stroke from 3 stroke centers, we developed a web portal feasibility platform for stroke studies (FePASS) to estimate proportions of eligible patients for acute stroke trials. We applied the FePASS resource to calculate the proportion of patients eligible for 4 recent stroke studies. RESULTS Sixty-one eligibility criteria were derived from 30 trials on acute ischemic stroke. FePASS, publicly available at http://fepass.uni-muenster.de, displays the proportion of patients in percent to assess the effect of varying values of relevant eligibility criteria, for example, age, symptom onset time, National Institutes of Health Stroke Scale, and prestroke modified Rankin Scale, on this proportion. The proportion of eligible patients for 4 recent stroke studies ranged from 2.1% to 11.3%. Slight variations of the inclusion criteria could substantially increase the proportion of eligible patients. CONCLUSIONS FePASS is an open access online resource to assess the effect of inclusion and exclusion criteria on the proportion of eligible patients for a stroke trial. FePASS can help to design stroke studies, optimize eligibility criteria, and to estimate the potential recruitment rate.

Relationship between hyperacute blood pressure and outcome after ischemic stroke: data from the VISTA Collaboration

Background and Purpose—High blood pressure (BP) is associated independently with poor outcome after acute ischemic stroke, although in most analyses “baseline” BP was measured 24 hours or more postictus, and not during the hyperacute period. Methods—Analyses included 1722 patients in hyperacute trials (recruitment 8 hours) from the Virtual Stroke International Stroke Trial Archive (VISTA) Collaboration. Data on BP at enrolment and after 1, 2, 16, 24, 48, and 72 hours, neurological impairment at 7 days (NIHSS), and functional outcome at 90 days (modified Rankin scale) were assessed using logistic regression models, adjusted for confounding variables; results are for 10-mm Hg change in BP. Results—Mean time to enrolment was 3.7 hours (range 1.0 to 7.9). High systolic BP (SBP) was significantly associated with increased neurological impairment (odds ratio, OR 1.06, 95% confidence interval, 95% CI 1.01 to 1.12), and poor functional outcome; odds ratios for both increased with later BP measurements made at up to 24 hours poststroke. Smaller (versus larger) declines in SBP over the first 24 hours were significantly associated with poor NIHSS scores (OR 1.16, 95% CI 1.05 to 1.27) and functional outcome (OR 1.23, 95% CI 1.13 to 1.34). A large variability in SBP was also associated with poor functional outcome. Conclusions—High SBP and large variability in SBP in the hyperacute stages of ischemic stroke are associated with increased neurological impairment and poor functional outcome, as are small falls in SBP over the first 24 hours.

Phenylephrine-induced hypertension during transient middle cerebral artery occlusion alleviates ischemic brain injury in spontaneously hypertensive rats

Arterial hypertension is a major risk factor for ischemic stroke. However, the management of preexisting hypertension is still controversial in the treatment of acute stroke in hypertensive patients. The present study evaluates the influence of preserving hypertension during focal cerebral ischemia on stroke outcome in a rat model of chronic hypertension, the spontaneously hypertensive rats (SHR). Focal cerebral ischemia was induced by transient (1 h) occlusion of the middle cerebral artery, during which mean arterial blood pressure was maintained at normotension (110-120 mm Hg, group 1, n=6) or hypertension (160-170 mm Hg, group 2, n=6) using phenylephrine. T2-, diffusion- and perfusion-weighted MRI were performed serially at five different time points: before and during ischemia, and at 1, 4 and 7 days after ischemia. Lesion volume and brain edema were estimated from apparent diffusion coefficient maps and T2-weighted images. Regional cerebral blood flow (rCBF) was measured within and outside the perfusion deficient lesion and in the corresponding regions of the contralesional hemisphere. Neurological deficits were evaluated after reperfusion. Infarct volume, edema, and neurological deficits were significantly reduced in group 2 vs. group 1. In addition, higher values and rapid restoration of rCBF were observed in group 2, while rCBF in both hemispheres was significantly decreased in group 1. Maintaining preexisting hypertension alleviates ischemic brain injury in SHR by increasing collateral circulation to the ischemic region and allowing rapid restoration of rCBF. The data suggest that maintaining preexisting hypertension is a valuable approach to managing hypertensive patients suffering from acute ischemic stroke. Published by Elsevier B.V.