Ioannis Christou

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.

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 patien...

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.

Intravenous Tissue Plasminogen Activator and Flow Improvement in Acute Ischemic Stroke Patients with Internal Carotid Artery Occlusion

Background and Purpose. It has been suggested that intravenous tissue plasminogen activator (TPA) would not lyse the large thrombus associated with internal carotid artery (ICA) occlusion and, therefore, would be ineffective in this setting. Vascular imaging, safety, and outcome of TPA therapy for ICA occlusion is not well described. Our goal was to determine the site of occlusion, early recanalization after TPA infusion, and its relationship to outcome. Methods. We reviewed our database of all stroke patients treated with IV TPA between July 1997 and July 1999. We identified all cases with carotid occlusion suggested by transcranial Doppler (TCD) and angiography. Occlusion and recanalization were assessed by site including proximal ICA (prICA), terminal ICA (tICA), and middle cerebral artery (MCA). Baseline National Institutes of Health Stroke Scale (NIHSS) scores and follow‐up Rankin scores were obtained. Results. We treated 20 patients with carotid occlusion (age 63.9 ± 10.8 years, 11 males, 9 females). Time to TPA infusion after stroke onset was 128 ± 66 minutes. Baseline NIHSS scores were 16.4 ± 5.4. Time to follow‐up was 3.5 ± 4.9 months (2 patients were lost to follow‐up). Occlusion sites were prICA 40%, tICA 70%, and concurrent MCA 45%. Multiple sites were involved in 10/20 patients (50%). Among patients with pretreatment and posttreatment vascular imaging studies (n= 18), recanalization in the prICA and tICA was complete in 10%, partial in 16%, and none in 74%. MCA recanalization was complete in 35%, partial in 24%, and none in 41%. At follow‐up, Rankin 0–1 was found in 8 patients (44%), Rankin 2–3 in 3 (17%), and Rankin 4–5 in 3 (17%). Mortality was 22% (n= 4) including 1 fatal intracerebral hemorrhage. Improvement was closely related to resumption of MCA flow (P < .01). Conclusions. Most patients did not recanalize their ICA occlusion after intravenous TPA therapy. However, recanalization of associated proximal MCA clot, found in 45% of our patients, or improved MCA collateral flow was strongly associated with good outcome.

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</=0.003. Parameters localizing anterior circulation occlusion were stenotic terminal ICA velocities 46% versus 10% in patent vessels; flow diversion to perforators 73% versus 1.8%; OA 70. 6% versus 5.6%; ACoA 78.6% versus 8.2%; PCoA 71.4% versus 8.5%, all at P<0.05. In patients with basilar artery (BA) occlusion, ABAW were found in 80% versus 3% (patent BA); flow diversion to anterior vessels in 60% versus 5.7%; BA flow reversal in 20% versus 0%; and PCoA in 100% versus 13.7%, all at P<0.001. No individual parameters differentiated BA from the terminal vertebral occlusion. CONCLUSIONS Specific TCD findings are common with major arterial occlusion and can be used to broaden diagnostic batteries and improve the predictive value of noninvasive screening in stroke patients. TCD findings useful to localize anterior circulation occlusion include collaterals, abnormal waveforms or velocities, and flow diversion to perforators.

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.

Screening for intracranial stenosis with transcranial Doppler: the accuracy of mean flow velocity thresholds.

Background. Patients with 50% intracranial arterial stenosis may require more intensive therapies for stroke prevention. Transcranial Doppler (TCD) is a convenient noninvasive screen for intracranial stenosis. The accuracy of different mean flow velocity (MFV) thresholds for determining the degree of stenosis remains uncertain. Methods. The authors prospectively compared the accuracy of TCD criteria and MFV thresholds to magnetic resonance, computed tomography, and digital subtraction angiography in patients with symptoms of recent or remote stroke or transient ischemic attack. Stenosis on angiography was measured as 0%, <50%, or ≥50% diameter reduction. Results. Of 136 consecutive patients, 33 (24%) had distal internal carotid artery (ICA), middle cerebral artery (MCA), posterior cerebral artery, or basilar artery stenosis on angiography (14 patients [10%] were excluded due to incomplete TCD examinations, mainly from a lack of temporal windows). TCD showed 31 true‐positive, 9 false‐positive, 2 false‐negative, and 94 true‐negative studies. For all vessels, TCD had a sensitivity of 93.9% (confidence interval [CI] = 89%‐98%), a specificity of 91.2% (CI = 87%‐96%), a positive predictive value (PPV) of 77.5%, and a negative predictive value (NPV) of 97.9%. The trade‐off in sensitivity and specificity for MCA MFV thresholds was as follows: MFV ≥80 cm/s had a sensitivity of 100%, a specificity of 96.9% (CI = 94%‐99%), a PPV of 84%, and an NPV of 100%. MFV≥100 cm/s had a sensitivity of 100%, a specificity of 97.9% (CI = 96%‐99%), a PPV of 88.8%, and an NPV of 94.9%. MFV≥120 cm/s had a sensitivity of 68.7% (CI = 61%‐78%), a specificity of 100%, a PPV of 100%, and an NPV of 94.9%. Reasons for false‐positive findings include collateralization of flow in the presence of proximal ICA stenosis and prestenotic to stenotic MCA velocity ratios of 1:≤2. Conclusion. TCD is both sensitive and specific in identifying ≥50% intracranial arterial stenosis. A MFV threshold cutoff of 100 cm/s has an optimal sensitivity and specificity trade‐off for ≥50% MCA stenosis. To help avoid false‐positive results, a prestenotic to stenotic MCA velocity ratio of 1:≥2 should be used in addition to the MFV threshold.

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 (≤ 0.6 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 ≥ 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 ≥ 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.

Evolution of Rapid Middle Cerebral Artery Recanalization During Intravenous Thrombolysis for Acute Ischemic Stroke

Intravenous recombinant tissue plasminogen activator (rtPA) is thought to benefit patients with acute ischemic stroke by producing early reperfusion.1 Transcranial Doppler (TCD) is a noninvasive method that can monitor the recanalization process in real time when occlusion occurs in the proximal intracranial vessels. We present our findings during rtPA infusion in a 56-year-old man with acute ischemic stroke to illustrate the time course of changes that occur in a middle cerebral artery (MCA) stem occlusion treated by intravenous thrombolysis. We used a 2-MHz portable unit (Multigon 500 mol/L) with a pulse-wave transducer mounted on a head frame (Marc 500, Spencer Technologies) …