A video-oculographic study of acute vestibular syndromes.

OBJECTIVES: To quantitate the vestibulo-ocular reflex (VOR) gain in patients with acute vestibular neuritis (VN) and repeat this daily using a portable video head impulse test device to assess vestibular recovery in the acute stage of VN. MATERIALS AND METHODS: We enrolled adults with symptoms and signs of VN presenting to the emergency department within 48 h of symptom onset. We recorded the eye movement response to rapid head impulses using the ICS Impulse(™) video head impulse test device on each day of their hospital admission. RESULTS: There were eight patients (75% men, aged 35-85 years) who had marked variation in their initial vestibulo-ocular reflex gains. Three patients had vestibulo-ocular reflex gains in the normal range initially, despite having physical signs of VN. Two patients had initial contralesional gains below the normal range, associated with markedly reduced ipsilesional gains. Most patients' vestibulo-ocular reflex gains increased during admission, but four patients' ipsilesional gains remained in the abnormal range. Patients with lower vestibulo-ocular reflex gains were less likely to improve into the normal range. No patient with initially abnormal VOR gain recovered normal vestibulo-ocular reflex gain along with resolution of physical signs. CONCLUSION: Early video head impulse testing in the emergency department and each day of admission is feasible and well tolerated. There is marked variation in VOR gain in patients with symptoms and signs of VN, and low initial VOR gains are a predictor for low VOR gains on subsequent days. Improvement in VOR gains was seen in most patients.

Prediction of the final infarct volume within 6 h of stroke using single photon emission computed tomography with technetium-99m hexamethylpropylene amine oxime.

BACKGROUND: A simple method to predict the final infarct volume within 6 h of onset of hemispheric ischemic stroke based on the measurement of cerebral blood flow (CBF) using single photon emission computed tomography (SPECT) with techneticum-99m hexamethylpropylene amine oxime ((99m)Tc-HMPAO) was investigated in a clinical model involving patients without definite early reperfusion or clinical recovery. METHODS: A group of 16 patients (group 1) was used to establish the methodology, which was then validated in a second group of 14 patients (group 2). The final infarct volume was defined using computed tomography (CT) performed at least 7 days after stroke. The relative CBF threshold value, expressed as a percentage of the mean contralateral hemispheric value, which most closely estimated the final infarct size on coregistered CT was established for each patient. RESULTS: The mean threshold CBF value for group 1 was 63.7%. When this value was used to predict infarct size in group 2, a close correlation was observed between the actual and the estimated sizes (r = 0.973, p < 0.0001). This value was not time dependent. CONCLUSIONS: If no significant early reperfusion or clinical recovery occurs, a CBF threshold value of 63.7% on (99m)Tc-HMPAO SPECT performed within 6 h of stroke onset will reliably predict the final infarct size.

Nimodipine and perfusion changes after stroke.

BACKGROUND AND PURPOSE: Meta-analysis of previous trials of oral nimodipine in acute stroke has suggested a benefit when commenced within 12 hours of onset. We sought to study the effect of oral nimodipine on reperfusion after acute stroke and the relation between reperfusion and outcome. METHODS: Fifty patients with acute middle cerebral artery territory cortical infarction were blindly randomized within 12 hours of onset to either oral nimodipine (30 mg every 6 hours) or placebo. Treatment was continued for 2 weeks. Cerebral blood flow was assessed with the use of 99mTc-hexamethylpropyleneamine oxime single-photon emission CT before therapy, 24 hours later, and at 3 months. Hypoperfusion was measured by a validated volumetric technique. Neurological impairment and functional outcome were assessed with the Canadian Neurological Scale and Barthel Index, respectively. Tissue loss was measured with CT at 3 months. Four patients were excluded from analysis for technical reasons. RESULTS: Twenty-three patients received nimodipine, and 23 received placebo. In the nimodipine group, there was early reperfusion that was not maintained at outcome (P=0.01). In the placebo group, mean infarct hypoperfusion volumes showed no overall change. Nonnutritional reperfusion in nimodipine-treated patients was associated with adverse neurological (P=0.05) and functional outcome (P=0.06). There was, however, no difference in clinical outcome between the 2 groups. CONCLUSIONS: Oral nimodipine administered within 12 hours enhanced acute reperfusion, but this was largely nonnutritional. Larger studies using a shorter treatment delay are required to evaluate the clinical efficacy of nimodipine in acute ischemic stroke.

Spontaneous reperfusion after ischemic stroke is associated with improved outcome.

BACKGROUND AND PURPOSE: The rationale behind thrombolytic therapy in acute ischemic stroke is penumbral salvage by rapid restoration of cerebral blood flow. The relationship, however, between early reperfusion (potentially composed of both nutritional and nonnutritional components) and outcome remains unclear. METHODS: To establish the relationship between reperfusion parameters and outcome variables (Canadian Neurological Scale, Barthel Index, outcome CT scans), we used 99Tc-hexamethylpropyleneamine oxime (99Tc-HMPAO) single-photon emission CT (SPECT) to examine 41 acute ischemic stroke patients. All patients had at least 2 SPECT studies (24 with 3 studies), and none had been treated with thrombolytic or other acute investigational drugs. RESULTS: A total of 106 studies were performed. Mean time to acute study was 9.2 hours; that for subacute study was 42 hours and for outcome study was 150 days. Hypoperfusion (HP) volumes at each of the 3 time points correlated with outcome clinical state and final infarct size. Both early reperfusion (61% of patients) and nutritional reperfusion alone (56%), which is early reperfusion maintained at outcome, were associated with improvement in clinical state and better functional outcome. Early HP volume change (acute minus subacute HP volume) and total HP volume change (acute minus outcome HP volume) also correlated with clinical improvement and better outcome. CONCLUSIONS: This study establishes the benefit of spontaneous reperfusion after ischemic stroke and emphasizes the prognostic value of HP deficit volumes. 99Tc-HMPAO SPECT may be used to screen patients and group them according to perfusion deficit in acute stroke trials, thereby decreasing patient numbers required to show drug effect.

Streptokinase in acute stroke: effect on reperfusion and recanalization. Australian Streptokinase Trial Study Group.

The Australian Streptokinase Trial was a randomized, double-blind, placebo-controlled trial, in which streptokinase (SK, 1.5 million IU I.V.) was given within 4 hours of stroke onset. In a subset of 37 patients, 99mTc-labeled D,L-hexamethylpropylene amine oxime single-photon emission computed tomography (SPECT) and/or transcranial Doppler (TCD) studies were performed before and after therapy to test the hypothesis that SK may improve the hemodynamic measures of reperfusion/recanalization rates (TCD parameter) within 24 hours. Eighteen patients received SK and 19 placebo. Baseline characteristics were similar in both groups, and there were no differences in clinical outcomes assessed at 3 months after stroke. Although there was no increase in the group mean perfusion defect or volume on SPECT after thrombolytic therapy, a larger number of patients demonstrating the combined end point of reperfusion or recanalization was seen in the SK group (13/14, 93%) than in the placebo group (7/14, 50%; p = 0.01). Although SK given within 4 hours of acute ischemic stroke appears to improve arterial patency/tissue reperfusion, this effect is neither early nor extensive enough to influence overall clinical outcome.

Volumetric analysis of cerebral hypoperfusion on SPECT: validation and reliability.

UNLABELLED: A method of volumetric analysis of hypoperfusion on 99mTc-labeled hexamethylpropylene amine oxime SPECT has been developed. This analysis integrates both the size and severity of perfusion reduction, yielding an equivalent volume of cortical tissue having zero blood flow, or the effective hypoperfusion volume. This study aimed to validate the methodology in vitro using the Hoffman brain phantom and two different camera systems, to examine the relationship between spatial resolution and accuracy of volume measurement and to assess the interobserver variability in SPECT studies of stroke patients. METHODS: Simulated cortical lesions of three different sizes were sequentially incorporated into the Hoffman brain phantom and imaged using both single- and triple-head camera systems. For each system and for each lesion size, successive acquisitions were performed using three progressively larger radii of camera rotation. The hypoperfusion volume for each study was measured three times by a blinded observer, and the percentage difference from the true lesion volume was then calculated. SPECT studies of 32 stroke patients were independently analyzed by two blinded observers. RESULTS: At the smallest radii of rotation, mean (s.d.) percentage difference between observed and true volumes was 0.90% (4.80%) for the triple-head and 4.50% (11.58%) for the single-head system. The degree of overestimation was similar for both systems. Percentage overestimation was strongly associated with radius of rotation (B = 0.71 +/- 0.32, p = 0.04 for the triple-head system; B = 1.26 +/- 0.55, p = 0.03 for the single-head system) but not with lesion size. The mean difference between hypoperfusion volumes of stroke patients obtained by two observers was 0.045 (3.240) cm3, which was not significant. CONCLUSION: This study has shown that this technique of volumetric analysis of regional hypoperfusion on SPECT is both highly accurate and reproducible between two different camera systems. The degree of overestimation chiefly relates to diminishing spatial resolution. Despite some element of subjectivity, the interobserver variability is negligible.

Streptokinase increases luxury perfusion after stroke.

BACKGROUND AND PURPOSE: Recent acute stroke trials have reported that intravenous streptokinase is associated with an increased risk of adverse outcomes. We aimed to study the effect of streptokinase on the nature of reperfusion and the relation between reperfusion and clinical outcome. METHODS: We studied 24 patients in the Australian Streptokinase Trial with acute middle cerebral cortical infarction using 99mTc-hexamethylpropyleneamine oxime single-photon emission CT. Eleven of the 24 patients were scanned before therapy and again 24 hours later. The remaining 13 were scanned once either before therapy (1 patient) or after therapy (12 patients). All patients had outcome scans after 3 months. Infarct hypoperfusion was measured with a validated volumetric technique. Neurological impairment and functional outcome were assessed with the Canadian Neurological Scale and the Barthel Index, respectively. RESULTS: Fifteen patients received streptokinase and 9 received placebo. There was no difference in early reperfusion between streptokinase and placebo. However, streptokinase was associated with a greater amount of nonnutritional reperfusion than was placebo (P = .04). This luxury perfusion was associated with poor functional outcome (P = .02). CONCLUSIONS: This study suggests that streptokinase augments luxury perfusion after stroke. Luxury perfusion is associated with a worse outcome, which might be due in part to reperfusion injury.

Microemboli during carotid angiography. Association with stroke risk factors or subsequent magnetic resonance imaging changes?

BACKGROUND AND PURPOSE: Carotid angiography is associated with a 1% risk of major stroke. Recently, transcranial Doppler ultrasonography (TCD) has shown cerebral microemboli during carotid angiography. To determine their significance, we correlated the number of microemboli during angiography with clinical characteristics, angiography findings, and preangiography and postangiography cerebral magnetic resonance imaging (MRI). METHODS: One middle cerebral artery was monitored with TCD in 24 patients during angiography for carotid territory ischemia. The number of microemboli was correlated with angiographic and clinical characteristics. T2-weighted cerebral MRI was performed before and < or = 48 hours after angiography, and the number of new ischemic lesions was determined in a blinded review. RESULTS: Microemboli were seen in all patients, with an average of 51 per procedure (range, 12 to 154). The majority of microemboli had signal characteristics typical of air. Sixteen of the 24 patients had both preangiography and postangiography MRI. One of 24 patients had an angiographic stroke, with a single new thalamic lesion on MRI. No other patient had a new lesion. The microembolus count correlated with the angiographic contrast volume (P < .001) but not with any other radiological or clinical characteristic. CONCLUSIONS: This study confirmed the presence of numerous cerebral microemboli during carotid angiography. The microembolic signal characteristics and the correlation with contrast volume indicate that introduced air is the cause. These microemboli are usually clinically silent and do not lead to new changes on cerebral MRI.

Prediction of functional outcome and tissue loss in acute cortical infarction.

OBJECTIVE: 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. DESIGN: A prospective study of acute stroke predictors and outcome measurements in a cohort of sequential hospitalized patients. 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. MAIN OUTCOME MEASURES: Mortality, Barthel Index, and volumetric measurement of infarct size on computed tomography 3 months after stroke. RESULTS: 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). CONCLUSIONS: 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.

BACKGROUND AND PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.