Outcome Barthel Index Research Articles

EPO for stroke therapy - Is there a future for further clinical development?

EPO for stroke therapy - Is there a future for further clinical development?

Recombinant Human Erythropoietin in the Treatment of Acute Ischemic Stroke

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. 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. 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. 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.

Somatosensory Evoked Potentials as a Predictor for Functional Recovery of the Upper Limb in Patients with Stroke

Predicting motor recovery in the arm of patients with stroke is generally based on clinical examination. However, neurophysiologic measures may also have a predictive value. We sought to assess the value of somatosensory evoked potentials (SSEPs) in predicting motor recovery of the upper limb and to determine whether any of the SSEPs components can predict the severity of the deficit so that it can document the size of the stroke (lacunar or large-vessel stroke). In all, 22 patients who had had a first-ever stroke and presented with obvious motor deficit of the arm were examined in terms of 3 clinical variables (motor performance, muscle tone, and overall disability) and for SSEPs. Clinical (Medical Research Council [MRC] scale and Barthel index scores) and neurophysiologic examinations were done at entry to the study (first week poststroke) and 3 months after stroke. Significantly low mean MRC scale score was found at first week versus after 3 months of stroke and in patients with large-vessel as compared with lacunar stroke both at first week and after 3 months. The mean Barthel index score was significantly higher after 3 months than at first week, whereas it was significantly lower in large-vessel as compared with lacunar stroke both at first week and after 3 months of stroke. Significantly prolonged N(20) latency, low peak-to-peak amplitude (PPA), and low amplitude ratio were found in patients with stroke as compared with control subjects. None of the neurophysiologic parameters were different in the patients with stroke between first week and third month. The MRC score and PPA were correlated well with the outcome MRC and Barthel index scores after 3 months. N(20) latency correlates with the outcome MRC score but not with the outcome Barthel index score. Interestingly, the N(20) latency was significantly different in lacunar from large-vessel stroke. The muscle power (MRC score) is the main outcome predictor in patients with stroke. PPA is the main SSEPs component with high prognostic value in stroke. The SSEPs N(20) latency can predict (even roughly) the size of cerebral infarction (whether lacunar or large-vessel stroke).

Prediction of Functional Outcome and Tissue Loss in Acute Cortical Infarction

To compare the acute Allen's Prognostic Score, Canadian Neurological Score, and subacute Barthel Index as predictors of outcome functional status and infarct size at 3 months in patients with acute cortical infarction. A prospective study of acute stroke predictors and outcome measurements in a cohort of sequential hospitalized patients. Fifty-one patients with acute cortical infarction and without previous disability assessed 24 hours after onset with Allen's Prognostic Score and the Canadian Neurological Score and at 7 days with the Barthel Index. Mortality, Barthel Index, and volumetric measurement of infarct size on computed tomography 3 months after stroke. There were seven deaths. The outcome Barthel Index was measured in all 44 survivors, of whom 29 had computed tomography at the time outcome was determined. In a multivariate analysis, functional outcome was best predicted by Allen's Prognostic Score, a score of less than -15 having a sensitivity of 82% and specificity of 97% in predicting a poor outcome (Barthel Index, < or = 12 or death). Volumetric tissue loss was predicted only by Allen's Prognostic Score (r = .62, P < .001). Allen's Prognostic Score is a robust predictor of both functional outcome and tissue loss in acute cortical infarction and has a potentially important role in the analysis of the results of acute stroke intervention trials.

Crossed Cerebellar Diaschisis and Brain Recovery After Stroke

Although crossed cerebellar diaschisis is well recognized after stroke, there is controversy concerning its clinical correlations and serial changes, and little is known about its prognostic value. We studied crossed cerebellar diaschisis and cerebral hypoperfusion in 47 patients with acute middle cerebral cortical infarction using 99mTc-hexamethylpropyleneamine oxime and single-photon emission computed tomography within 72 hours of stroke onset. Thirty-one of these patients had outcome studies at 3 months; 15 of the 31 underwent an additional scan after acetazolamide injection. Tissue loss was determined with computed tomography, performed at outcome in 28 patients. Clinical stroke severity was assessed with the Canadian Neurological Scale and Barthel Index. Cerebellar blood flow asymmetry was studied in 22 healthy, age-matched control subjects. Cerebellar blood flow asymmetry was significant in patients (mean +/- SE, 9.76 +/- 0.78%; P < .001) but not in control subjects (-0.22 +/- 0.56%). Crossed cerebellar diaschisis was strongly associated with infarct hypoperfusion volume at both acute (regression coefficient +/- SEb, b = 6.76 +/- 0.65; P < .001) and outcome stages (b = 6.13 +/- 0.63; P < .001). Cross-sectionally over the first 72 hours, infarct hypoperfusion volume decreased by 2% for each hour from onset (P < .05), while crossed cerebellar diaschisis remained unchanged. Canadian Neurological Scale score at the acute stage was negatively associated with acute crossed cerebellar diaschisis (b = -0.10 +/- 0.05; P < .05) after allowing for infarct hypoperfusion volume. Crossed cerebellar diaschisis did not change between acute-stage, outcome, and postacetazolamide scans. Acute-stage crossed cerebellar diaschisis predicted outcome Barthel Index score (b = -0.28 +/- 0.14; P = .05) and tissue loss (b = 3.81 +/- 0.96; P < .001) but was no longer an independent prognostic factor after allowing for acute-stage infarct hypoperfusion volume. This study shows that crossed cerebellar diaschisis is a functional phenomenon that correlates with both stroke severity and infarct hypoperfusion volume and persists despite neurological recovery. Although acute-stage crossed cerebellar diaschisis has no prognostic value independent of acute-stage hypoperfusion volume, it might indicate the proportion of nutritional to nonnutritional perfusion at the infarct site and hence be useful in the evaluation of reperfusion therapies in the acute stage.

Cerebral hypoperfusion in stroke prognosis and brain recovery.

The value of acute cerebral blood flow measurements in stroke prognosis is controversial. No previous study has determined whether acute perfusion deficits independently add to a validated clinical prognostic score. We aimed to compare the value of acute hypoperfusion deficits with a quantitative clinical score in stroke prognosis and to correlate the changes in perfusion with brain recovery. Volumetric analysis of regional hypoperfusion was performed in 38 patients with middle cerebral infarction within 72 hours of onset by use of single photon emission computed tomography and 99mTc hexamethylpropylene amine oxime. Stroke severity was assessed by the Canadian Neurological Score and Barthel Index. Allen's prognostic score was determined acutely in all patients. Clinical outcome was evaluated in 36 of 38 patients, of whom 18 had repeat blood flow studies. Acute hypoperfusion correlated with both the outcome Barthel Index (P < .001, r = -.61) and Canadian Neurological Score (P < .001, r = -.64). Allen's score correlated better with both the outcome Barthel Index (P < .001, r = .80) and Canadian Neurological Score (P < .001, r = .81). Acute hypoperfusion deficits, after allowing for Allen's score, independently predicted neurological but not functional outcome. Despite overall neurological improvement, mean hypoperfusion increased on the repeat blood flow studies (P < .05). Volumetric analysis of acute regional hypoperfusion within 72 hours of onset predicts stroke outcome after 3 months, but Allen's score is a better prognostic method. Neurological recovery is not associated with chronic infarct reperfusion.