Predictors of fatal brain edema in massive hemispheric ischemic stroke.

BACKGROUND AND PURPOSE: Early identification of stroke patients at risk for fatal brain edema may be useful in selecting patients for aggressive interventions. Prior studies suggested that early nausea/vomiting and major hypodensity on baseline computed tomography (CT) were predictive of herniation. METHODS: This study was a retrospective multicenter case-control study of patients with large middle cerebral artery (MCA) strokes admitted within 48 hours of symptom onset. Medical records, laboratory data, and CT scans were analyzed. Cases, defined as patients who died of massive brain swelling, were compared with all remaining patients as controls. RESULTS: Two hundred one patients with large MCA strokes were identified: 94 (47%) died of brain swelling, 12 (6%) died of non-neurological causes, and 95 (47%) survived at day 30. Multivariable analysis, adjusted for age and clustered by center, identified the following predictors of fatal brain edema: history of hypertension (OR 3.0, 95% CI 1.2 to 7.6, P=0.02), history of heart failure (OR 2.1, 95% CI 1.5 to 3.0, P<0.001), elevated white blood cell count (OR 1.08 per 1000 white blood cells/microL, 95% CI 1.01 to 1.14, P=0.02), >50% MCA hypodensity (OR 6.3, 95% CI 3.5 to 11.6, P<0.001), and involvement of additional vascular territories (anterior cerebral artery, posterior cerebral artery, or anterior choroidal artery; OR 3.3, 95% CI 1.2 to 9.4, P=0.02). Initial level of consciousness, National Institutes of Health Stroke Scale score, early nausea/vomiting, and serum glucose were associated with neurological death in bivariable but not multivariable analyses. CONCLUSIONS: Among patients with large MCA infarctions, an increased risk of fatal brain edema is associated with history of hypertension or heart failure, increased baseline white blood cell count, major early CT hypodensity involving >50% of the MCA territory, and involvement of additional vascular territories. These data confirm and expand on prior research with a broad-based patient population. The presence of these risk factors identifies those stroke patients who may require aggressive therapeutic approaches.

Arterial status after intravenous TPA therapy for ischaemic stroke. A need for further interventions.

BACKGROUND: Intravenous tissue plasminogen activator (TPA) is an approved therapy for acute ischaemic stroke in the United States. We aimed to noninvasively monitor the therapy to determine arterial recanalisation and persisting vascular abnormalities. METHODS: We prospectively studied consecutive patients with symptoms of ischaemic stroke who received intravenous TPA and were monitored by 2 MHz transcranial Doppler (TCD) to determine occlusion and recanalisation (TIMI grades equivalent). For outcome assessment we used the National Institutes of Health Stroke Scale (NIHSS) score. RESULTS: Sixty patients were studied (age 71+/-15 years, pre-TPA NIHSS 18+/-6.1, TPA bolus at 141+/-68 min after stroke onset). The internal carotid artery (ICA) was occluded in 25%, middle cerebral artery (MCA) in 80%; combined (ICA+MCA) occlusion was found in 19%; and basilar artery (BA) was occluded in 7%. Also, 2% had normal TCD and 8% of patients had no temporal windows. Complete recanalisation on TCD of all insonated arteries was found in 19 patients (32%) at 44+/-22 min after a TPA bolus. However, 67% of MCA, 25% of BA, and all ICA occlusions did not completely recanalise (TIMI grades 0-2). If flow impairment persisted for more than two hours after a TPA bolus, these patients continued to have significant neurological deficits at 24 hours (15.0+/-8.2 vs 6.3+/-7.3 NIHSS points, p<0.001 in non-parametric statistics). High-grade residual stenoses with microembolic signals were seen on TCD in the MCA and BA (n=3) suggesting continuing clot dissolution. In patients without complete recanalisation (n=36, or 60%), TCD identified lesions potentially amenable to further interventions. CONCLUSIONS: Persisting arterial occlusion after intravenous TPA therapy leads to poor short-term outcome. Noninvasive monitoring of TPA therapy with TCD can identify these high-risk patients for combined interventions such as intra-arterial thrombolysis, mechanical clot disruption, stenting or anticoagulation.

A broad diagnostic battery for bedside transcranial Doppler to detect flow changes with internal carotid artery stenosis or occlusion.

BACKGROUND AND PURPOSE: The authors establish accuracy parameters of a broad diagnostic battery for bedside transcranial Doppler (TCD) to detect flow changes due to internal carotid artery (ICA) stenosis or occlusion. METHODS: The authors prospectively studied consecutive patients with stroke or transient ischemic attack referred for TCD. TCD was performed and interpreted at bedside using a standard insonation protocol. A broad diagnostic battery included major criteria: collateral flow signals, abnormal siphon or terminal carotid signals, and delayed systolic flow acceleration in the middle cerebral artery. Minor criteria included a unilateral decrease in pulsatility index (< or = 0.6 or < or = 70% of contralateral side), flow diversion signs, and compensatory velocity increase. Angiography or carotid duplex ultrasound (CDU) was used to grade the degree of carotid stenosis using North American criteria. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of TCD findings were determined. RESULTS: Seven hundred and twenty patients underwent TCD, of whom 517 (256 men and 261 women) had angiography and/or CDU within 8.8 +/- 0.9 days. Age was 63.1 +/- 15.7 years. For a 70% to 99% carotid stenosis or occlusion, TCD had sensitivity of 79.4%, specificity of 86.2%, PPV of 57.0%, NPV of 94.8%, and accuracy of 84.7%. For a 50% to 99% carotid stenosis or occlusion, TCD had sensitivity of 67.5%, specificity of 83.9%, PPV of 54.5%, NPV of 90.0%, and accuracy of 81.6%. TCD detected intracranial carotid lesions with 84.9% accuracy and extracranial carotid lesions with 84.4% accuracy (sensitivity of 88% and 79%, specificity of 85% and 86%, PPV of 24% and 54%, and NPV of 99% and 95%, respectively). The prevalence of the ophthalmic artery flow reversal was 36.4% in patients with > or = 70% stenosis or occlusion. If present, this finding indicated a proximal ICA lesion location in 97% of these patients. CONCLUSIONS: In symptomatic patients, bedside TCD can accurately detect flow changes consistent with hemodynamically significant ICA obstruction; however, TCD should not be a substitute for direct carotid evaluation. Because TCD is sensitive and specific for a > or = 70% carotid stenosis or occlusion in both extracranial and intracranial carotid segments, it can be used as a complementary test to refine other imaging findings and detect tandem lesions.

Thrombolysis in brain ischemia (TIBI) transcranial Doppler flow grades predict clinical severity, early recovery, and mortality in patients treated with intravenous tissue plasminogen activator.

BACKGROUND AND PURPOSE: TIMI angiographic classification measures coronary residual flow and recanalization. We developed a Thrombolysis in Brain Ischemia (TIBI) classification by using transcranial Doppler (TCD) to noninvasively monitor intracranial vessel residual flow signals. We examined whether the emergent TCD TIBI classification correlated with stroke severity and outcome in patients treated with intravenously administered tPA (IV-tPA). METHODS: TCD examination occurred acutely and on day 2. TIBI flows were determined at distal MCA and basilar artery depths, depending on occlusion site. TIBI waveforms were graded as follows: 0, absent; 1, minimal; 2, blunted; 3, dampened; 4, stenotic; and 5, normal. National Institutes of Health Stroke Scale (NIHSS) scores were obtained at baseline and 24 hours after administration of tPA. RESULTS: One hundred nine IV tPA patients were studied. Mean+/-SD age was 68+/-16 years; median NIHSS score before administration of tPA (pre-tPA) was 17.5. The tPA bolus was administered 143+/-58 minutes and the TCD examination 141+/-57 minutes after symptom onset. Pre-tPA NIHSS scores were higher in patients with TIBI grade 0 than TIBI grade 4 or 5 flow. TIBI flow improvement to grade 4 or 5 occurred in 35% of patients (19/54) with an initial grade of 0 or 1 and in 52% (12/23) with initial grade 2 or 3. The 24-hour NIHSS scores were higher in follow-up in patients with TIBI grade 0 or 1 than those with TIBI grade 4 or 5 flow. TIBI flow recovery correlated with NIHSS score improvement. Lack of flow recovery predicted worsening or no improvement. In-hospital mortality was 71% (5/7) for patients with posterior circulation occlusions; it was 22% (11/51) for patients with pre-tPA TIBI 0 or 1 compared with 5% (1/19) for those with pre-tPA TIBI 2 or 3 anterior circulation occlusions. CONCLUSIONS: Emergent TCD TIBI classification correlates with initial stroke severity, clinical recovery, and mortality in IV-tPA-treated stroke patients. A flow-grade improvement correlated with clinical improvement.

Timing of recanalization after tissue plasminogen activator therapy determined by transcranial doppler correlates with clinical recovery from ischemic stroke.

BACKGROUND: The duration of cerebral blood flow impairment correlates with irreversibility of brain damage in animal models of cerebral ischemia. Our aim was to correlate clinical recovery from stroke with the timing of arterial recanalization after therapy with intravenous tissue plasminogen activator (tPA). METHODS: Patients with symptoms of cerebral ischemia were treated with 0.9 mg/kg tPA IV within 3 hours after stroke onset (standard protocol) or with 0.6 mg/kg at 3 to 6 hours (an experimental institutional review board-approved protocol). National Institutes of Health Stroke Scale (NIHSS) scores were obtained before treatment, at the end of tPA infusion, and at 24 hours; Rankin Scores were obtained at long-term follow-up. Transcranial Doppler (TCD) was used to locate arterial occlusion before tPA and to monitor recanalization (Marc head frame, Spencer Technologies; Multigon 500M, DWL MultiDop-T). Recanalization on TCD was determined according to previously developed criteria. RESULTS: Forty patients were studied (age 70+/-16 years, baseline NIHSS score 18.6+/-6.2). A tPA bolus was administered at 132+/-54 minutes from symptom onset. Recanalization on TCD was found at the mean time of 251+/-171 minutes after stroke onset: complete recanalization occurred in 12 (30%) patients and partial recanalization occurred in 16 (40%) patients (maximum observation time 360 minutes). Recanalization occurred within 60 minutes of tPA bolus in 75% of patients who recanalized. The timing of recanalization inversely correlated with early improvement in the NIHSS scores within the next hour (polynomial curve, third order r(2)=0.429, P<0.01) as well as at 24 hours. Complete recanalization was common in patients who had follow-up Rankin Scores if 0 to 1 (P=0.006). No patients had early complete recovery if an occlusion persisted for >300 minutes. CONCLUSIONS: The timing of arterial recanalization after tPA therapy as determined with TCD correlates with clinical recovery from stroke and demonstrates a 300-minute window to achieve early complete recovery. These data parallel findings in animal models of cerebral ischemia and confirm the relevance of these models in the prediction of response to reperfusion therapy.

Transcranial doppler ultrasound criteria for recanalization after thrombolysis for middle cerebral artery stroke.

BACKGROUND AND PURPOSE: Transcranial Doppler (TCD) can demonstrate arterial occlusion and subsequent recanalization in acute ischemic stroke patients treated with intravenous tissue plasminogen activator (tPA). Limited data exist to assess the accuracy of recanalization by TCD criteria. METHODS: In patients with acute middle cerebral artery (MCA) occlusion treated with intravenous tPA, we compared posttreatment TCD with angiography (digital subtraction or magnetic resonance). On TCD, complete occlusion was defined by absent or minimal signals, partial occlusion by blunted or dampened signals, and recanalization by normal or stenotic signals. Angiography was evaluated with the Thrombolysis In Myocardial Ischemia (TIMI) grading scale. RESULTS: Twenty-five patients were studied (age 61+/-18 years, 16 men and 9 women). TCD was performed at 12+/-16 hours and angiography at 41+/-57 hours after stroke onset, with 52% of studies performed within 3 hours of each other. Recanalization on TCD had the following accuracy parameters compared with angiography: sensitivity 91%, specificity 93%, positive predictive value (PPV) 91%, and negative predictive value (NPV) 93%. To predict partial occlusion (TIMI grade II), TCD had sensitivity of 100%, specificity of 76%, PPV of 44%, and NPV of 100%. TCD predicted the presence of complete occlusion on angiography (TIMI grade 0 or I) with sensitivity of 50%, specificity of 100%, PPV of 100%, and NPV of 75%. TCD flow signals correlated with angiographic patency (chi(2)=24.2, P<0.001). CONCLUSIONS: Complete MCA recanalization on TCD accurately predicts angiographic findings. Although a return to normal flow dynamics on TCD was associated with complete angiographic resumption of flow, partial signal improvement on TCD corresponded with persistent occlusion on angiography.

High rate of complete recanalization and dramatic clinical recovery during tPA infusion when continuously monitored with 2-MHz transcranial doppler monitoring.

BACKGROUND AND PURPOSE: Clot dissolution with tissue plasminogen activator (tPA) can lead to early clinical recovery after stroke. Transcranial Doppler (TCD) with low MHz frequency can determine arterial occlusion and monitor recanalization and may potentiate thrombolysis. METHODS: Stroke patients receiving intravenous tPA were monitored during infusion with portable TCD (Multigon 500M; DWL MultiDop-T) and headframe (Marc series; Spencer Technologies). Residual flow signals were obtained from the clot location identified by TCD. National Institutes of Health Stroke Scale (NIHSS) scores were obtained before and after tPA infusion. RESULTS: Forty patients were studied (mean age 70+/-16 years, baseline NIHSS score 18.6+/-6.2, tPA bolus at 132+/-54 minutes from symptom onset). TCD monitoring started at 125+/-52 minutes and continued for the duration of tPA infusion. The middle cerebral artery was occluded in 30 patients, the internal carotid artery was occluded in 11 patients, the basilar artery was occluded in 3 patients, and occlusions were multiple in 7 patients; 4 patients had no windows; and 1 patient had a normal TCD. Recanalization on TCD was found at 45+/-20 minutes after tPA bolus: recanalization was complete in 12 (30%) and partial in 16 (40%) patients. Dramatic recovery during tPA infusion (total NIHSS score <3) occurred in 8 (20%) of all patients (baseline NIHSS range 6 to 22; all 8 had complete recanalization). Lack of improvement or worsening was associated with no recanalization, late recanalization, or reocclusion on TCD (C=0.811, P< or =0.01). Improvement by > or =10 NIHSS points or complete recovery was found in 30% of all patients at the end of tPA infusion and in 40% at 24 hours. Improvement by > or =4 NIHSS points was found in 62.5% of patients at 24 hours. CONCLUSIONS: Dramatic recovery during tPA therapy occurred in 20% of all patients when infusion was continuously monitored with TCD. Recovery was associated with recanalization on TCD, whereas no early improvement indicated persistent occlusion or reocclusion. At 24 hours, 40% of all patients improved by > or =10 NIHSS points or recovered completely. Ultrasonic energy transmission by TCD monitoring may expose more clot surface to tPA and facilitate thrombolysis and deserves a controlled trial as a way to potentiate the effect of tPA therapy.

Accuracy and criteria for localizing arterial occlusion with transcranial Doppler.

The authors determined transcranial Doppler (TCD) accuracy for the proximal internal carotid artery (ICA), distal ICA, proximal middle cerebral artery (MCA), distal MCA, anterior cerebral artery (ACA), posterior cerebral artery (PCA), terminal vertebral artery (tVA), and basilar artery (BA) occlusion in cerebral ischemia patients. Detailed diagnostic criteria were prospectively applied for TCD interpretation independent of angiographic findings. Of 320 consecutive patients referred to the neurosonology service with symptoms of cerebral ischemia, 190 (59%) patients also underwent angiography (MRA or DSA). 48 of those 190 patients had angiographic occlusion and 12 of those 48 patients had involvement of multiple vessels. Median time from TCD until angiography was performed was 1 hour (41 patients had angiography before TCD). TCD showed 40 true positive, 8 false negative, 8 false positive, and 134 true negative studies with sensitivity 83.0%, specificity 94.4%, positive predictive value 83.0%, negative predictive value 94.4%, and accuracy 91.6% to determine all sites of occlusion. Sensitivity for each individual occlusion site was: proximal ICA 94%, distal ICA 81%, MCA 93% tVA 56%, BA 60%. Specificity ranged from 96% to 98%. TCD is sensitive and specific in determining the site of the arterial occlusion using detailed diagnostic criteria, including proximal ICA and distal MCA lesions. TCD has the highest accuracy for ICA and MCA occlusions. If the results of TCD are normal, there is at least a 94% chance that angiographic studies will be negative.

Specific transcranial Doppler flow findings related to the presence and site of arterial occlusion.

BACKGROUND AND PURPOSE: Transcranial Doppler (TCD) can localize arterial occlusion in stroke patients. Our aim was to evaluate the frequency of specific TCD flow findings with different sites of arterial occlusion. METHODS: Using a standard insonation protocol, we prospectively evaluated the frequency of specific TCD findings in patients with or without proximal extracranial or intracranial occlusion determined by digital subtraction or MR angiography. RESULTS: Of 190 consecutive patients studied, angiography showed occlusion in 48 patients. With proximal internal carotid artery (ICA) occlusion, TCD showed abnormal middle cerebral artery (MCA) waveforms (AMCAW) in 66.7%, reversed ophthalmic artery (OA) in 70.6%, anterior cross-filling via anterior communicating artery (ACoA) in 78.6%, posterior communicating artery (PCoA) in 71.4%, and contralateral compensatory velocity increase (CVI) in 84.6% of patients. With distal ICA occlusion, TCD showed AMCAW in 88.9%, OA in 16.7%, ACoA in 50%, PCoA in 60%, and CVI in 88.9% of patients. With MCA occlusion, TCD showed AMCAW in 100%, OA in 23.5%, ACoA in 31.3%, PCoA in 23.1%, and CVI in 62.5%. With no anterior circulation occlusion at angiography, TCD showed these parameters in 1.8% to 17. 9%, chi(2) P

Deterioration following spontaneous improvement : sonographic findings in patients with acutely resolving symptoms of cerebral ischemia.

BACKGROUND AND PURPOSE: Some stroke patients will deteriorate following improvement (DFI), but the cause of such fluctuation is often unclear. While resolution of neurological deficits is usually related to spontaneous recanalization or restoration of collateral flow, vascular imaging in patients with DFI has not been well characterized. METHODS: We prospectively studied patients who presented with a focal neurological deficit that resolved spontaneously within 6 hours of symptom onset. Patients were evaluated with bedside transcranial Doppler (TCD). Digital subtraction angiography (DSA), computed tomographic angiography (CTA), or magnetic resonance angiography (MRA) were performed when feasible. DFI was defined as subsequent worsening of the neurological deficit by >/=4 National Institutes of Health Stroke Scale points within 24 hours of the initial symptom onset. RESULTS: We studied 50 consecutive patients presenting at 165+/-96 minutes from symptom onset. Mean age was 61+/-14 years; 50% were females. All patients had TCD at the time of presentation, and 68% had subsequent angiographic examinations (DSA 10%, CTA 4%, and MRA 44%). Overall, large-vessel occlusion on TCD was found in 16% of patients (n=8); stenosis was found in 18% (n=9); 54% (n=27) had normal studies; and 6 patients (12%) had no temporal windows. DFI occurred in 16% (n=8) of the 50 patients: in 62% of patients with TCD and angiographic evidence of occlusion, in 22% with stenosis, and in 4% with normal vascular studies (P<0.001, Phi=0.523, chi(2)=12.05). DFI occurred in 31% of patients with large-vessel atherosclerosis, 23% with cardioembolism, and 9% with small-vessel disease when stroke mechanisms were determined within 2 to 3 days after admission (P=0.2, NS). CONCLUSIONS: DFI is strongly associated with the presence of large-vessel occlusion or stenosis of either atherosclerotic or embolic origin. Normal vascular studies and lacunar events were associated with stable spontaneous resolution without subsequent fluctuation. Urgent vascular evaluation may help identify patients with resolving deficits and vascular lesions who may be candidates for new therapies to prevent subsequent deterioration.