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Appropriateness Criteria

Reference Study Type Patients/Events Study Objective(Purpose of Study) Study Results Study Quality
1. Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics--2015 update: a report from the American Heart Association. Circulation. 2015;131(4):e29-322. Review/Other-Dx N/A To provide heart disease and stroke statistics. No results stated in abstract. 4
2. Berkhemer OA, Fransen PS, Beumer D, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med 2015;372:11-20. Experimental-Tx 500 patients To assess whether intraarterial treatment plus usual care would be more effective than usual care alone in patients with a proximal arterial occlusion in the anterior cerebral circulation that could be treated intraarterially within 6 hours after symptom onset. The mean age was 65 years (range, 23 to 96), and 445 patients (89.0%) were treated with intravenous alteplase before randomization. Retrievable stents were used in 190 of the 233 patients (81.5%) assigned to intraarterial treatment. The adjusted common odds ratio was 1.67 (95% confidence interval [CI], 1.21 to 2.30). There was an absolute difference of 13.5 percentage points (95% CI, 5.9 to 21.2) in the rate of functional independence (modified Rankin score, 0 to 2) in favor of the intervention (32.6% vs. 19.1%). There were no significant differences in mortality or the occurrence of symptomatic intracerebral hemorrhage. 1
3. Campbell BC, Mitchell PJ, Kleinig TJ, et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 372(11):1009-18, 2015 Mar 12. Experimental-Tx 70 patients To test whether more advanced imaging selection, recently developed devices, and earlier intervention improve outcomes. The trial was stopped early because of efficacy after 70 patients had undergone randomization (35 patients in each group). The percentage of ischemic territory that had undergone reperfusion at 24 hours was greater in the endovascular-therapy group than in the alteplase-only group (median, 100% vs. 37%; P<0.001). Endovascular therapy, initiated at a median of 210 minutes after the onset of stroke, increased early neurologic improvement at 3 days (80% vs. 37%, P=0.002) and improved the functional outcome at 90 days, with more patients achieving functional independence (score of 0 to 2 on the modified Rankin scale, 71% vs. 40%; P=0.01). There were no significant differences in rates of death or symptomatic intracerebral hemorrhage. 1
4. Goyal M, Demchuk AM, Menon BK, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 372(11):1019-30, 2015 Mar 12. Experimental-Tx 316 patients To evaluate rapid endovascular treatment in addition to standard care in patients with acute ischemic stroke with a small infarct core, aproximal intracranial arterial occlusion, and moderate-to-good collateral circulation. The trial was stopped early because of efficacy. At 22 centers worldwide, 316 participants were enrolled, of whom 238 received intravenous alteplase (120 in the intervention group and 118 in the control group). In the intervention group, the median time from study CT of the head to first reperfusion was 84 minutes. The rate of functional independence (90-day modified Rankin score of 0 to 2) was increased with the intervention (53.0%, vs. 29.3% in the control group; P<0.001). The primary outcome favored the intervention (common odds ratio, 2.6; 95% confidence interval, 1.7 to 3.8; P<0.001), and the intervention was associated with reduced mortality (10.4%, vs. 19.0% in the control group; P=0.04). Symptomatic intracerebral hemorrhage occurred in 3.6% of participants in intervention group and 2.7% of participants in control group (P=0.75). 1
5. Saver JL, Goyal M, Bonafe A, et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med. 372(24):2285-95, 2015 Jun 11. Experimental-Tx 196 patients To establish the efficacy and safety of rapid neurovascular thrombectomy with the stent retriever in conjunction with intravenous t-PA versus intravenous t-PA alone in patients with acute ischemic stroke. The study was stopped early because of efficacy. At 39 centers, 196 patients underwent randomization (98 patients in each group). In the intervention group, the median time from qualifying imaging to groin puncture was 57 minutes, and the rate of substantial reperfusion at the end of the procedure was 88%. Thrombectomy with the stent retriever plus intravenous t-PA reduced disability at 90 days over the entire range of scores on the modified Rankin scale (P<0.001). The rate of functional independence (modified Rankin scale score, 0 to 2) was higher in the intervention group than in the control group (60% vs. 35%, P<0.001). There were no significant between-group differences in 90-day mortality (9% vs. 12%, P=0.50) or symptomatic intracranial hemorrhage (0% vs. 3%, P=0.12). 1
6. American College of Radiology. Manual on Contrast Media. Available at: https://www.acr.org/Clinical-Resources/Contrast-Manual. Review/Other-Dx N/A To assist radiologists in recognizing and managing risks associated with the use of contrast media. No abstract available. 4
7. Expert Panel on MR Safety, Kanal E, Barkovich AJ, et al. ACR guidance document on MR safe practices: 2013. J Magn Reson Imaging. 37(3):501-30, 2013 Mar. Review/Other-Dx N/A To help guide MR practitioners regarding MR safety issues and provide a basis for them to develop and implement their own MR policies and practices. No abstract available. 4
8. Edjlali M, Roca P, Rabrait C, et al. MR selective flow-tracking cartography: a postprocessing procedure applied to four-dimensional flow MR imaging for complete characterization of cranial dural arteriovenous fistulas. Radiology. 270(1):261-8, 2014 Jan. Observational-Dx 8 patients To assess the feasibility of a selective flow-tracking cartographic procedure applied to four-dimensional (4D) flow imaging and to demonstrate its usefulness in the characterization of dural arteriovenous fistulas (DAVFs). Interreader agreement for shunt location on MR images was perfect (kappa = 1), with good-to-excellent interreader agreement for arterial feeder vessel identification (kappa = 0.97; 95% CI = 0.92, 1.0), and matched in all cases with shunt location defined at DSA. There was good-to-excellent agreement between MR cartography and DSA in the definition of the main feeding arteries (kappa = 0.92; 95% CI = 0.83, 1.0), presence of retrograde flow in dural sinuses (kappa = 1), presence of retrograde cortical venous drainage (kappa = 1), presence of venous ectasia (kappa = 1), and final Cognard classification of DAVFs (kappa = 1, standard error = 0.35). 1
9. Gandhi D, Chen J, Pearl M, Huang J, Gemmete JJ, Kathuria S. Intracranial dural arteriovenous fistulas: classification, imaging findings, and treatment. [Review]. AJNR Am J Neuroradiol. 33(6):1007-13, 2012 Jun. Review/Other-Dx N/A To review intracranial dural areteriovenous fistulas. Intracranial DAVFs are pathologic dural-based shunts and account for 10%-15% of all intracranial arteriovenous malformations. These malformations derive their arterial supply primarily from meningeal vessels, and the venous drainage is either via dural venous sinuses or through the cortical veins. DAVFs have a reported association with dural sinus thrombosis, venous hypertension, previous craniotomy, and trauma, though many lesions are idiopathic. The diagnosis is dependent on a high level of clinical suspicion and high-resolution imaging. Cross-sectional imaging techniques by using CT and MR imaging aid in the diagnosis, but conventional angiography remains the most accurate method for complete characterization and classification of DAVFs. The pattern of venous drainage observed on dynamic vascular imaging determines the type of DAVF and correlates with the severity of symptoms and the risk of hemorrhage. 4
10. Iryo Y, Hirai T, Kai Y, et al. Intracranial dural arteriovenous fistulas: evaluation with 3-T four-dimensional MR angiography using arterial spin labeling. Radiology. 2014;271(1):193-199 Observational-Dx 9 patients To evaluate whether 3-T four-dimensional (4D) arterial spin-labeling (ASL)-based magnetic resonance (MR) angiography is useful for the evaluation of shunt lesions in patients with intracranial dural arteriovenous fistulas (AVFs). On all 4D ASL MR angiographic images, the major intracranial arteries were demonstrated at a temporal resolution of 300 milliseconds. Interobserver agreement was excellent for the fistula site (kappa = 1.00; 95% confidence interval [CI]: 1.00, 1.00), moderate for the main arterial feeders (kappa = 0.53; 95% CI: 0.08, 0.98), and good for venous drainage (kappa = 0.77; 95% CI: 0.35, 1.00). Intermodality agreement was excellent for the fistula site and venous drainage (kappa = 1.00; 95% CI: 1.00, 1.00) and good for the main arterial feeders (kappa = 0.80; 95% CI: 0.58, 1.00). 2
11. Nishimura S, Hirai T, Sasao A, et al. Evaluation of dural arteriovenous fistulas with 4D contrast-enhanced MR angiography at 3T. AJNR Am J Neuroradiol. 31(1):80-5, 2010 Jan. Observational-Dx 18 consecutive patients To test the hypothesis that 4D-CE-MRA at 3T enables the same characterization of intracranial DAVFs as DSA. At DSA, 8 fistulas were located at the transverse sigmoid sinus; 8, at the cavernous sinus; and 2, at the sinus adjacent to the foramen magnum. Interobserver agreement was fair for the main arterial feeders (kappa = 0.59), excellent for the fistula site (kappa = 0.91), and good for venous drainage (kappa = 0.86). Intermodality agreement was moderate for the main arterial feeders (kappa = 0.68) and excellent for the fistula site (kappa = 1.0) and venous drainage (kappa = 1.0). 2
12. Wu H, Block WF, Turski PA, et al. Noncontrast dynamic 3D intracranial MR angiography using pseudo-continuous arterial spin labeling (PCASL) and accelerated 3D radial acquisition. J Magn Reson Imaging. 2014;39(5):1320-1326. Review/Other-Dx 5 patients To develop a novel dynamic 3D noncontrast magnetic resonance angiography (MRA) technique that combines dynamic pseudo-continuous arterial spin labeling (dynamic PCASL), accelerated 3D radial sampling (VIPR), and time-of-arrival (TOA) mapping to provide quantitative assessment of arterial flow. Digital simulations demonstrated reduced image artifacts and improved TOA accuracy using radial acquisition over Cartesian. TOA mapping accuracy is more sensitive to sampling window length than time spacing. Dynamic PCASL MRA depicted seven of eight arterial pedicles, and accurately measured the AVM nidus size when the nidus was compact. The venous drainage in the AVM patients was not consistently visualized. 4
13. Telischak NA, Detre JA, Zaharchuk G. Arterial spin labeling MRI: clinical applications in the brain. J Magn Reson Imaging. 2015;41(5):1165-1180. Review/Other-Dx N/A To outline the various ASL techniques including advantages and disadvantages of each, methodology for clinical interpretation, and clinical applications with specific examples. Visualization of cerebral blood flow (CBF) has become an important part of neuroimaging for a wide range of diseases. Arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) sequences are increasingly being used to provide MR-based CBF quantification without the need for contrast administration, and can be obtained in conjunction with a structural MRI study. ASL MRI is useful for evaluating cerebrovascular disease including arterio-occlusive disease, vascular shunts, for assessing primary and secondary malignancy, and as a biomarker for neuronal metabolism in other disorders such as seizures and neurodegeneration. 4
14. Easton JD, Saver JL, Albers GW, et al. Definition and evaluation of transient ischemic attack: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease. The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists. Stroke 2009;40:2276-93. Review/Other-Dx N/A To review and synthesize recent scientific advances regarding the definition, urgency, and evaluation of TIA. Neuroimaging studies, particularly diffusion-perfusion–weighted MRI, have fundamentally altered our understanding of the pathophysiology of TIA. In routine clinical practice, MRI permits confirmation of focal ischemia rather than another process as the cause of a patient’s deficit, improves accuracy of diagnosis of the vascular localization and cause of TIA, and assesses the extent of preexisting cerebrovascular injury. Accordingly, MRI, including diffusion sequences, should now be considered a preferred diagnostic test in the investigation of the patient with potential TIAs. Additional diagnostic workup, including vessel imaging, cardiac evaluation, and laboratory testing, should be completed according to the AHA acute stroke guidelines. 4
15. Kidwell CS, Warach S. Acute ischemic cerebrovascular syndrome: diagnostic criteria. Stroke. 2003;34(12):2995-2998. Review/Other-Dx N/A To review acute ischemic cerebrovascular syndrome. Clinical trials testing new treatments for acute ischemic stroke or secondary stroke prevention should limit enrollment to patients with "definite" AICS whenever feasible. 4
16. Restrepo L, Jacobs MA, Barker PB, Wityk RJ. Assessment of transient ischemic attack with diffusion- and perfusion-weighted imaging. AJNR Am J Neuroradiol 2004;25:1645-52. Review/Other-Dx 22 patients To test the hypothesis that PW imaging would substantiate the diagnosis of brain ischemia in an additional proportion of patients with transient neurologic symptoms. MR imaging was abnormal in 15 patients (68%): 12 had abnormal DW imaging, four had both DW and PW imaging defects (all with a mismatch) and three had an isolated PW imaging abnormality. There were no differences in symptom duration, stroke etiology or cardiovascular risk factors between patients with abnormal MR imaging and those with unremarkable scan. Patients with mismatch were more likely to need conventional angiography or other cerebrovascular procedures. 4
17. Johnston SC, Gress DR, Browner WS, Sidney S. Short-term prognosis after emergency department diagnosis of TIA. JAMA. 2000;284(22):2901-2906. Observational-Dx 1707 patients To determine the short-term risk of stroke and other adverse events after emergency department (ED) diagnosis of TIA. During the 90 days after index TIA, 180 patients (10.5%) returned to the ED with a stroke, 91 of which occurred in the first 2 days. Five factors were independently associated with stroke: age greater than 60 years (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.1-2.7; P=.01), diabetes mellitus (OR, 2.0; 95% CI, 1.4-2.9; P<.001), symptom duration longer than 10 minutes (OR, 2.3; 95% CI, 1.3-4.2; P=.005), weakness (OR, 1.9; 95% CI, 1.4-2.6; P<.001), and speech impairment (OR, 1.5; 95% CI, 1.1-2.1; P=.01). Stroke or other adverse events occurred in 428 patients (25.1%) in the 90 days after the TIA and included 44 hospitalizations for cardiovascular events (2.6%), 45 deaths (2.6%), and 216 recurrent TIAs (12.7%). 3
18. Eliasziw M, Kennedy J, Hill MD, Buchan AM, Barnett HJ, North American Symptomatic Carotid Endarterectomy Trial G. Early risk of stroke after a transient ischemic attack in patients with internal carotid artery disease. CMAJ 2004;170:1105-9. Experimental-Tx 1129 patients To quantify the early risk of stroke after a TIA in patients with internal carotid artery disease. For patients with a first-recorded hemispheric TIA (n = 603), the 90-day risk of ipsilateral stroke was 20.1% (95% confidence interval [CI] 17.0%-23.2%), higher than the 2.3% risk (95% CI 1.0%-3.6%) for patients with a hemispheric stroke (n = 526). The 2-day risks were 5.5% and 0.0%, respectively. Patients with more severe stenosis of the internal carotid artery (> 70%) appeared to be at no greater risk of stroke than patients with lesser degrees of stenosis (adjusted hazard ratio 1.1, 95% CI 0.7-1.7). Infarct on brain imaging (adjusted hazard ratio 2.1, 95% CI 1.5-3.0) and the presence of intracranial major-artery disease (adjusted hazard ratio 1.9, 95% CI 1.3-2.7) doubled the early risk of stroke in patients with a hemispheric TIA. 1
19. Kleindorfer D, Panagos P, Pancioli A, et al. Incidence and short-term prognosis of transient ischemic attack in a population-based study. Stroke. 2005;36(4):720-723. Review/Other-Dx 927 patients To present the incidence and short-term prognosis of TIA within a large population with a significant proportion of minorities with out-of-hospital TIA. The overall race, age, and gender-adjusted incidence rate for TIA within our population was 83 per 100,000, with age, race, and gender adjusted to the 1990 US population. Blacks and men had significantly higher rates of TIA than whites and women. Risk of stroke after TIA was 14.6% at 3 months, and risk of TIA/stroke/death was 25.2%. Age, race, and sex were not associated with recurrent TIA or subsequent stroke in our population, but age was associated with mortality. 4
20. Wu CM, McLaughlin K, Lorenzetti DL, Hill MD, Manns BJ, Ghali WA. Early risk of stroke after transient ischemic attack: a systematic review and meta-analysis. Arch Intern Med. 2007;167(22):2417-2422. Meta-analysis 11 studies To conduct a systematic review and meta-analysis of observational studies estimating the risk of stroke at 2, 30, and 90 days after TIA and to explore clinical and methodological factors that may explain variability in findings across studies. Based on a random effects model, the pooled early risk of stroke was 3.5%, 8.0%, and 9.2% at 2, 30, and 90 days after TIA, respectively. Studies reported higher risks when the methodology involved active ascertainment of stroke outcome compared with passive ascertainment. Early risk of stroke was 9.9%, 13.4%, and 17.3% at 2, 30, and 90 days, respectively, when only studies with active outcome ascertainment were considered. M
21. Clark TG, Murphy MF, Rothwell PM. Long term risks of stroke, myocardial infarction, and vascular death in "low risk" patients with a non-recent transient ischaemic attack. J Neurol Neurosurg Psychiatry. 2003;74(5):577-580. Observational-Dx 290 patients To determine the long term risks of stroke and other vascular events in patients with TIA who survive the initial high risk period. Median time since last TIA was 3.8 years (interquartile range, 2.2 to 5.8 years). The risk of major vascular events was constant through time. The 10 year risk of first stroke was 18.8% (95% confidence interval (CI), 13.6 to 23.7; 45 events). The 10 year risk of myocardial infarction or death from coronary heart disease was 27.8% (95% CI, 21.8 to 33.3; 67 events) and there was a significant excess of fatal coronary events compared with that expected in the general population (SMR = 1.47; 95% CI, 1.10 to 1.93; p = 0.009). A total of 114 patients had at least one major vascular event, with a 10 year risk of any first stroke, myocardial infarction, or vascular death of 42.8% (95% CI, 36.4 to 48.5). 3
22. van Wijk I, Kappelle LJ, van Gijn J, et al. Long-term survival and vascular event risk after transient ischaemic attack or minor ischaemic stroke: a cohort study. Lancet. 2005;365(9477):2098-2104. Observational-Tx 2473 participants To assess the survival status and occurrence of vascular events in 2473 participants of the Dutch TIA Trial (recruitment in 1986-89; arterial cause of cerebral ischaemia). Follow-up was complete in 2447 (99%) patients. After a mean follow-up of 10.1 years, 1489 (60%) patients had died and 1336 (54%) had had at least one vascular event. 10-year risk of death was 42.7% (95% CI 40.8-44.7). Age and sex-adjusted hazard ratios were 3.33 (2.97-3.73) for age over 65 years, 2.10 (1.79-2.48) for diabetes, 1.77 (1.45-2.15) for claudication, 1.94 (1.42-2.65) for previous peripheral vascular surgery, and 1.50 (1.31-1.71) for pathological Q waves on baseline electrocardiogram. 10-year risk of a vascular event was 44.1% (42.0-46.1). After falling in the first 3 years, yearly risk of a vascular event increased over time. Predictive factors for risk of vascular events were similar to those for risk of death. 1
23. Del Zoppo GJ, Saver JL, Jauch EC, Adams HP, Jr. Expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator: a science advisory from the American Heart Association/American Stroke Association. Stroke. 2009;40(8):2945-2948. Review/Other-Tx N/A Guidelines on the expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator. No results stated in abstract. 4
24. Neumann-Haefelin T, Wittsack HJ, Wenserski F, et al. Diffusion- and perfusion-weighted MRI. The DWI/PWI mismatch region in acute stroke. Stroke. 1999;30(8):1591-1597. Observational-Dx 20 patients To evaluate the PWI/DWI mismatch region in acute stroke patients and find parameters indicative of both infarct progression and functional impairment. In 80% of patients the acute DWI lesion was surrounded by regions with abnormal TTP delays (PWI>DWI lesion). A TTP delay of >/=6 s in the mismatch region was found to be associated with lesion enlargement between the initial and follow-up MRI scans. Lesions increased in 9 of 12 patients (75%) in whom the area with TTP delay >/=6 s was larger than the DWI lesion, but they increased in only 1 of 8 (12.5%) of the remaining patients, in whom the area with a TTP delay >/=6 s was smaller than the DWI lesion. The volume of the regions with TTP delays of >/=4 s correlated better with ESS (r=-0.88, P<0.001) than other PWI (or DWI) volumes, which indicated that a TTP delay of approximately 4 s might be the threshold for functional impairment of brain tissue. 2
25. Ribo M, Molina CA, Rovira A, et al. Safety and efficacy of intravenous tissue plasminogen activator stroke treatment in the 3- to 6-hour window using multimodal transcranial Doppler/MRI selection protocol. Stroke. 2005;36(3):602-606. Observational-Tx 135 patients To study safety and efficacy of tPA treatment in the 3- to 6-hour window using multimodal transcranial Doppler (TCD)/MRI selection criteria. Of 135 patients, 56 were in the 3- to 6-hour window. Only 13 (23%) patients within 3 to 6 hours did not meet MRI inclusion criteria. Finally, 122 patients were treated with tPA: A, 79 (65%); B, 43 (35%). Median time to treatment was: A, 136 minutes (range 60 to 180); B, 223 (185 to 360). There were no differences in demographic parameters, baseline NIHSS (A, 17; B, 17; P=0.89), and occlusion location (proximal MCA A, 65.8%; B, 74.4%; P=0.28). Recanalization rates at 2 hours were similar (A, 49.3%; B, 55.2%; P=0.33), as were hemorrhagic transformation rates (asymptomatic: A, 18.7%, B, 26.6%, P=0.43; symptomatic: A, 3.75%, B, 2.38%, P=0.66). Improvement at discharge was similar in both groups (NIHSS dropped 6.3 points [A] versus 6.1 [B]; P=0.86). However, the number of patients who benefited from treatment was slightly higher in the 3- to 6-hour group (A, 58.2%; B, 76.2%; P=0.05), whereas the same rate of patients worsened (A, 11.4%; B, 7.1%; P=0.46). At 3 months, the rate of independent patients was: A, 42% versus B, 38% (P=0.74). 2
26. Fargen KM, Meyers PM, Khatri P, Mocco J. Improvements in recanalization with modern stroke therapy: a review of prospective ischemic stroke trials during the last two decades. [Review]. J Neurointerv Surg. 5(6):506-11, 2013 Nov. Review/Other-Dx 13 trials To present a review of prospective acute ischemic stroke trials reported in a peer-reviewed forum during the last 20 years to provide insight into the general direction of this rapidly evolving field. Thirteen prospective trials were included. Regression analyses demonstrated no appreciable change in the median NIH Stroke Scale score of subjects at the time of enrollment since 1995 (p=0.44) and no appreciable improvements in good outcome based on a modified Rankin score of 0-2 at 90 days (p=0.66) or mortality at 90 days (p=0.55). A significant increase in time from onset of symptoms to treatment among enrolled patients was noted from 1995 to 2012 (p=0.03). In addition, a significant improvement in recanalization/reperfusion was noted over the last two decades (p=0.02). 4
27. Mokin M, Khalessi AA, Mocco J, et al. Endovascular treatment of acute ischemic stroke: the end or just the beginning?. [Review]. Neurosurg. focus. 36(1):E5, 2014 Jan. Review/Other-Dx 3 trials To review the evolution of endovascular treatment strategies for the treatment of acute stroke and provide their interpretation of findings and potential limitations of the three recently published randomized trials. Various endovascular intraarterial approaches are available for treating patients with acute ischemic stroke who present with severe neurological deficits. Three recent randomized trials-Interventional Management of Stroke (IMS) III, Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE), and Synthesis Expansion: A Randomized Controlled Trial on Intra-Arterial Versus Intravenous Thrombolysis in Acute Ischemic Stroke (SYNTHESIS Expansion)-evaluated the efficacy of endovascular treatment of acute ischemic stroke and, after failing to demonstrate any significant clinical benefit of endovascular therapies, raised concerns and questions in the medical community regarding the future of endovascular treatment for acute ischemic stroke. 4
28. Nogueira RG, Lutsep HL, Gupta R, et al. Trevo versus Merci retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke (TREVO 2): a randomised trial. Lancet. 2012;380(9849):1231-1240. Experimental-Tx 178 patients To compare the efficacy and safety of mechanical thrombectomy with the Trevo Retriever with that of the Merci Retriever in the arterial revascularisation of patients with acute ischaemic stroke. Between Feb 3, 2011, and Dec 1, 2011, 88 patients were randomly assigned to the Trevo Retriever group and 90 patients to Merci Retriever group. 76 (86%) patients in the Trevo group and 54 (60%) in the Merci group met the primary endpoint after the assigned device was used (odds ratio 4.22, 95% CI 1.92-9.69; p(superiority)<0.0001). Incidence of the primary safety endpoint did not differ between groups (13 [15%] patients in the Trevo group vs 21 [23%] in the Merci group; p=0.1826). 1
29. Saver JL, Jahan R, Levy EI, et al. Solitaire flow restoration device versus the Merci Retriever in patients with acute ischaemic stroke (SWIFT): a randomised, parallel-group, non-inferiority trial. Lancet. 2012;380(9849):1241-1249. Experimental-Tx 113 total patients To compare the efficacy and safety of Solitaire with the standard, predicate mechanical thrombectomy device, the Merci Retrieval System. Between February, 2010, and February, 2011, we randomly allocated 58 patients to the Solitaire group and 55 patients to the Merci group. The primary efficacy outcome was achieved more often in the Solitaire group than it was in the Merci group (61%vs 24%; difference 37% [95% CI 19-53], odds ratio [OR] 4.87 [95% CI 2.14-11.10]; p(non-inferiority)<0.0001, p(superiority)=0.0001). More patients had good 3-month neurological outcome with Solitaire than with Merci (58%vs 33%; difference 25% [6-43], OR 2.78 [1.25-6.22]; p(non-inferiority)=0.0001, p(superiority)=0.02). 90-day mortality was lower in the Solitaire group than it was in the Merci group (17 vs 38; difference -21% [-39 to -3], OR 0.34 [0.14-0.81]; p(non-inferiority)=0.0001, p(superiority)=0.02). 1
30. Broderick JP, Palesch YY, Demchuk AM, et al. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med. 2013;368(10):893-903. Experimental-Tx 656 participants To conduct the IMS III trial, an international, phase 3, randomized, open-label clinical trial with a blinded outcome, to test the approach of intravenous t-PA followed by protocolapproved endovascular treatment, as compared with standard intravenous t-PA. The study was stopped early because of futility after 656 participants had undergone randomization (434 patients to endovascular therapy and 222 to intravenous t-PA alone). The proportion of participants with a modified Rankin score of 2 or less at 90 days did not differ significantly according to treatment (40.8% with endovascular therapy and 38.7% with intravenous t-PA; absolute adjusted difference, 1.5 percentage points; 95% confidence interval [CI], -6.1 to 9.1, with adjustment for the National Institutes of Health Stroke Scale [NIHSS] score [8-19, indicating moderately severe stroke, or >/=20, indicating severe stroke]), nor were there significant differences for the predefined subgroups of patients with an NIHSS score of 20 or higher (6.8 percentage points; 95% CI, -4.4 to 18.1) and those with a score of 19 or lower (-1.0 percentage point; 95% CI, -10.8 to 8.8). Findings in the endovascular-therapy and intravenous t-PA groups were similar for mortality at 90 days (19.1% and 21.6%, respectively; P=0.52) and the proportion of patients with symptomatic intracerebral hemorrhage within 30 hours after initiation of t-PA (6.2% and 5.9%, respectively; P=0.83). 1
31. Ciccone A, Valvassori L, Nichelatti M, et al. Endovascular treatment for acute ischemic stroke. N Engl J Med. 368(10):904-13, 2013 Mar 07. Experimental-Tx 362 patients To investigate whether endovascular treatment, including the options of a mechanical device and intraarterial t-PA, is more effective than the currently available treatment with intravenous t-PA. A total of 181 patients were assigned to receive endovascular therapy, and 181 intravenous t-PA. The median time from stroke onset to the start of treatment was 3.75 hours for endovascular therapy and 2.75 hours for intravenous t-PA (P<0.001). At 3 months, 55 patients in the endovascular-therapy group (30.4%) and 63 in the intravenous t-PA group (34.8%) were alive without disability (odds ratio adjusted for age, sex, stroke severity, and atrial fibrillation status at baseline, 0.71; 95% confidence interval, 0.44 to 1.14; P=0.16). Fatal or nonfatal symptomatic intracranial hemorrhage within 7 days occurred in 6% of the patients in each group, and there were no significant differences between groups in the rates of other serious adverse events or the case fatality rate. 1
32. Kidwell CS, Jahan R, Gornbein J, et al. A trial of imaging selection and endovascular treatment for ischemic stroke. N Engl J Med. 2013;368(10):914-923. Experimental-Tx 127 patients To randomly assign patients within 8 hours after the onset of largevessel, anterior-circulation strokes to undergo mechanical embolectomy (Merci Retriever or Penumbra System) or receive standard care. Among 118 eligible patients, the mean age was 65.5 years, the mean time to enrollment was 5.5 hours, and 58% had a favorable penumbral pattern. Revascularization in the embolectomy group was achieved in 67% of the patients. Ninety-day mortality was 21%, and the rate of symptomatic intracranial hemorrhage was 4%; neither rate differed across groups. Among all patients, mean scores on the modified Rankin scale did not differ between embolectomy and standard care (3.9 vs. 3.9, P=0.99). Embolectomy was not superior to standard care in patients with either a favorable penumbral pattern (mean score, 3.9 vs. 3.4; P=0.23) or a nonpenumbral pattern (mean score, 4.0 vs. 4.4; P=0.32). In the primary analysis of scores on the 90-day modified Rankin scale, there was no interaction between the pretreatment imaging pattern and treatment assignment (P=0.14). 1
33. Andersen KK, Olsen TS, Dehlendorff C, Kammersgaard LP. Hemorrhagic and ischemic strokes compared: stroke severity, mortality, and risk factors. Stroke. 2009;40(6):2068-2072. Review/Other-Tx 39,484 patients To study differences and similarities between patients with HS and IS with respect to risk factors, stroke severity, and survival. Of the patients 3993 (10.1%) had HS. Stroke severity was almost linearly related to the probability of having HS (2% in patients with the mildest stroke and 30% in those with the most severe strokes). Factors favoring ischemic strokes vs HS were diabetes, atrial fibrillation, previous myocardial infarction, previous stroke, and intermittent arterial claudication. Smoking and alcohol consumption favored HS, whereas age, sex, and hypertension did not herald stroke type. Compared with ischemic strokes, HS was associated with an overall higher mortality risk (HR, 1.564; 95% CI, 1.441-1.696). The increased risk was, however, time-dependent; initially, risk was 4-fold, after 1 week it was 2.5-fold, and after 3 weeks it was 1.5-fold. After 3 months stroke type did not correlate to mortality. 4
34. Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. JAMA 1995;273:1421-8. Experimental-Tx 1659 patients To determine whether the addition of carotid endarterectomy to aggressive medical management can reduce the incidence of cerebral infarction in patients with asymptomatic carotid artery stenosis. After a median follow-up of 2.7 years, with 4657 patient-years of observation, the aggregate risk over 5 years for ipsilateral stroke and any perioperative stroke or death was estimated to be 5.1% for surgical patients and 11.0% for patients treated medically (aggregate risk reduction of 53% [95% confidence interval, 22% to 72%]). 1
35. Barnett HJ, Taylor DW, Eliasziw M, et al. Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med 1998;339:1415-25. Experimental-Tx 2226 patients To assess the benefit of carotid endarterectomy in patients with symptomatic moderate stenosis, defined as stenosis of less than 70 percent. Among patients with stenosis of 50 to 69 percent, the five-year rate of any ipsilateral stroke (failure rate) was 15.7 percent among patients treated surgically and 22.2 percent among those treated medically (P=0.045); to prevent one ipsilateral stroke during the five-year period, 15 patients would have to be treated with carotid endarterectomy. Among patients with less than 50 percent stenosis, the failure rate was not significantly lower in the group treated with endarterectomy (14.9 percent) than in the medically treated group (18.7 percent, P=0.16). Among the patients with severe stenosis who underwent endarterectomy, the 30-day rate of death or disabling ipsilateral stroke persisting at 90 days was 2.1 percent; this rate increased to only 6.7 percent at 8 years. Benefit was greatest among men, patients with recent stroke as the qualifying event, and patients with hemispheric symptoms. 1
36. Brott TG, Hobson RW, 2nd, Howard G, et al. Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med 2010;363:11-23. Experimental-Tx 2522 patients To compare the outcomes of carotid-artery stenting with those of carotid endarterectomy among patients with symptomatic or asymptomatic extracranial carotid stenosis. For 2502 patients over a median follow-up period of 2.5 years, there was no significant difference in the estimated 4-year rates of the primary end point between the stenting group and the endarterectomy group (7.2% and 6.8%, respectively; hazard ratio with stenting, 1.11; 95% confidence interval, 0.81 to 1.51; P=0.51). There was no differential treatment effect with regard to the primary end point according to symptomatic status (P=0.84) or sex (P=0.34). The 4-year rate of stroke or death was 6.4% with stenting and 4.7% with endarterectomy (hazard ratio, 1.50; P=0.03); the rates among symptomatic patients were 8.0% and 6.4% (hazard ratio, 1.37; P=0.14), and the rates among asymptomatic patients were 4.5% and 2.7% (hazard ratio, 1.86; P=0.07), respectively. Periprocedural rates of individual components of the end points differed between the stenting group and the endarterectomy group: for death (0.7% vs. 0.3%, P=0.18), for stroke (4.1% vs. 2.3%, P=0.01), and for myocardial infarction (1.1% vs. 2.3%, P=0.03). After this period, the incidences of ipsilateral stroke with stenting and with endarterectomy were similarly low (2.0% and 2.4%, respectively; P=0.85). 1
37. Grotta JC. Clinical practice. Carotid stenosis. N Engl J Med. 2013;369(12):1143-1150. Review/Other-Dx N/A To review the clinical practice of carotid stenosis. Carotid intervention (endarterectomy or stenting, depending on the clinical setting) is recommended generally in symptomatic patients with stenosis of more than 70% and in selected asymptomatic low-risk patients and symptomatic patients with stenosis of 50 to 69%. 4
38. Halliday A, Harrison M, Hayter E, et al. 10-year stroke prevention after successful carotid endarterectomy for asymptomatic stenosis (ACST-1): a multicentre randomised trial. Lancet 2010;376:1074-84. Experimental-Tx 3120 patients To assess the long-term effects of successful CEA. 1560 patients were allocated immediate CEA versus 1560 allocated deferral of any carotid procedure. The proportions operated on while still asymptomatic were 89.7% versus 4.8% at 1 year (and 92.1%vs 16.5% at 5 years). Perioperative risk of stroke or death within 30 days was 3.0% (95% CI 2.4-3.9; 26 non-disabling strokes plus 34 disabling or fatal perioperative events in 1979 CEAs). Excluding perioperative events and non-stroke mortality, stroke risks (immediate vs deferred CEA) were 4.1% versus 10.0% at 5 years (gain 5.9%, 95% CI 4.0-7.8) and 10.8% versus 16.9% at 10 years (gain 6.1%, 2.7-9.4); ratio of stroke incidence rates 0.54, 95% CI 0.43-0.68, p<0.0001. 62 versus 104 had a disabling or fatal stroke, and 37 versus 84 others had a non-disabling stroke. Combining perioperative events and strokes, net risks were 6.9% versus 10.9% at 5 years (gain 4.1%, 2.0-6.2) and 13.4% versus 17.9% at 10 years (gain 4.6%, 1.2-7.9). Medication was similar in both groups; throughout the study, most were on antithrombotic and antihypertensive therapy. Net benefits were significant both for those on lipid-lowering therapy and for those not, and both for men and for women up to 75 years of age at entry (although not for older patients). 1
39. Rothwell PM, Eliasziw M, Gutnikov SA, et al. Analysis of pooled data from the randomised controlled trials of endarterectomy for symptomatic carotid stenosis. Lancet 2003;361:107-16. Review/Other-Tx 6092 patients To determine with as much precision as possible the effectiveness and durability of endarterectomy by degree of carotid stenosis. Risks of main outcomes in both treatment groups and effects of surgery did not differ between trials. Data for 6092 patients, with 35000 patient-years of follow-up, were therefore pooled. Surgery increased the 5-year risk of ipsilateral ischaemic stroke in patients with less than 30% stenosis (n=1746, absolute risk reduction -2.2%, p=0.05), had no effect in patients with 30-49% stenosis (1429, 3.2%, p=0.6), was of marginal benefit in those with 50-69% stenosis (1549, 4.6%, p=0.04), and was highly beneficial in those with 70% stenosis or greater without near-occlusion (1095, 16.0%, p<0.001). There was a trend towards benefit from surgery in patients with near-occlusion at 2 years' follow-up (262, 5.6%, p=0.19), but no benefit at 5 years (-1.7%, p=0.9). 4
40. Wardlaw JM, Chappell FM, Best JJ, et al. Non-invasive imaging compared with intra-arterial angiography in the diagnosis of symptomatic carotid stenosis: a meta-analysis. Lancet 2006;367:1503-12. Meta-analysis 41 studies To systematically review the accuracy of non-invasive imaging compared with intra-arterial angiography for diagnosing carotid stenosis in patients with carotid territory ischaemic symptoms. In 41 included studies (2541 patients, 4876 arteries), contrast-enhanced MR angiography was more sensitive (0.94, 95% CI 0.88-0.97) and specific (0.93, 95% CI 0.89-0.96) for 70-99% stenosis than Doppler ultrasound, MR angiography, and CT angiography (sensitivities 0.89, 0.88, 0.76; specificities 0.84, 0.84, 0.94, respectively). Data for 50-69% stenoses and combinations of non-invasive tests were sparse and unreliable. There was heterogeneity between studies and evidence of publication bias. M
41. Jahromi AS, Cina CS, Liu Y, Clase CM. Sensitivity and specificity of color duplex ultrasound measurement in the estimation of internal carotid artery stenosis: a systematic review and meta-analysis. J Vasc Surg 2005;41:962-72. Meta-analysis 47 studies To conduct a systematic review and meta-analysis of the relation between the degree of internal carotid artery stenosis by duplex ultrasound criteria and degree of stenosis by angiography. Variables extracted included internal carotid artery peak systolic velocity, internal carotid artery end diastolic velocity, internal carotid artery/common carotid artery peak systolic velocity ratio, sensitivity and specificity of duplex ultrasound scanning for internal carotid artery stenosis by angiography. The Standards for Reporting of Diagnostic Accuracy (STARD) criteria were used to assess study quality. Sensitivity and specificity for duplex ultrasound criteria were combined as weighted means by using a random effects model. The threshold of peak systolic velocity >/=130 cm/s is associated with sensitivity of 98% (95% confidence intervals [CI], 97% to 100%) and specificity of 88% (95% CI, 76% to 100%) in the identification of angiographic stenosis of >/=50%. For the diagnosis of angiographic stenosis of >/=70%, a peak systolic velocity >/=200 cm/s has a sensitivity of 90% (95% CI, 84% to 94%) and a specificity of 94% (95% CI, 88% to 97%). For each duplex ultrasound threshold, measurement properties vary widely between laboratories, and the magnitude of the variation is clinically important. The heterogeneity observed in the measurement properties of duplex ultrasound may be caused by differences in patients, study design, equipment, techniques or training. M
42. Barth A, Arnold M, Mattle HP, Schroth G, Remonda L. Contrast-enhanced 3-D MRA in decision making for carotid endarterectomy: a 6-year experience. Cerebrovasc Dis. 2006;21(5-6):393-400. Review/Other-Dx 327 patients To present the radiological characteristics and clinical results of a series of patients operated on the basis of combined ultrasonography (US)/MRA. Among 327 patients, preoperative MRA was performed in 278 (85%), DSA in 44 (13.5%) and CT angiography in 5 (1.5%). Most of DSA studies were performed as emergency for preparation of endovascular therapy or for reasons other than carotid stenosis. Eleven additional DSA (3.3%) complemented US/MRA, mostly because diverging diagnosis of subocclusion of ICA. No direct morbidity or intraoperative difficulty was related to preoperative MRA. Combined mortality/major morbidity rate was 0.9% (3 patients) and minor morbidity rate 5.5% (18 patients). 4
43. Honish C, Sadanand V, Fladeland D, Chow V, Pirouzmand F. The reliability of ultrasound measurements of carotid stenosis compared to MRA and DSA. Can J Neurol Sci. 2005;32(4):465-471. Observational-Dx 140 carotid arteries To compare reliability of MRA and US modes with DSA in determining degree of internal carotid artery stenosis. US grading of carotid stenosis can be made more reliable by choosing appropriate parameters. The best combination of sensitivity and specificity for stenosis > 70% in our hospital was seen at PSV > 173 cm/s (sensitivity 0.87, specificity 0.8, Positive Predictive Value (PPV) 0.70, Negative Predictive Value (NPV) 0.93, kappa 0.64 and weighted kappa 0.71). MRA kappa was 0.78, (sensitivity 0.75, specificity 1.0, PPV 1.0, NPV 0.85). 2
44. U-King-Im JM, Hollingworth W, Trivedi RA, et al. Cost-effectiveness of diagnostic strategies prior to carotid endarterectomy. Ann Neurol. 2005;58(4):506-515. Review/Other-Dx 167 patients To assess the long-term cost-effectiveness of five alternative diagnostic strategies for identification of severe carotid stenosis in recently symptomatic patients. A "selective" strategy, whereby all patients receive DUS and CEMRA (only proceeding to DSA if the CEMRA is positive and the DUS is negative), was most cost-effective. This was both the cheapest imaging and treatment strategy (35,205 dollars per patient) and yielded 6.1590 quality-adjusted life years (QALYs), higher than three alternative imaging strategies. Probabilistic sensitivity analysis demonstrated that there was less than a 10% probability that imaging with either DUS or DSA alone are cost-effective at the conventional 50,000 dollars/QALY threshold. In conclusion, DSA is not cost-effective in the routine diagnostic workup of most patients. DUS, with additional imaging in the form of CEMRA, is recommended, with a strategy of "CEMRA and selective DUS review" being shown to be the optimal imaging strategy. 4
45. Korn A, Bender B, Thomas C, et al. Dual energy CTA of the carotid bifurcation: advantage of plaque subtraction for assessment of grade of the stenosis and morphology. Eur J Radiol. 2011;80(2):e120-125. Observational-Dx 36 patients with a total of 46 stenoses To evaluate the diagnostic value of 3D-MIP images after subtraction of bone and calcified plaques (PBS) using dual energy CT for the assessment of carotid bifurcation stenoses. Grade of the stenosis could be evaluated in all 46 cases in DSA, axMPR and 3D-MIP after PBS. However, in 25 cases grade of the stenosis was not assessable prior to PBS. The average grade of the stenosis increased from DSA (81.4%) to axMPR (83.5%) to 3D-MIP before and after PBS (86.5% and 85.6%). The amount of pseudo-occlusions increased in concordance with the grade of the stenosis (0<9<16). Using 3D-MIP reconstructions, plaque morphology could be evaluated in 32/46 stenoses before PBS and in 44/46 cases after PBS. 2
46. Thomas C, Korn A, Ketelsen D, et al. Automatic lumen segmentation in calcified plaques: dual-energy CT versus standard reconstructions in comparison with digital subtraction angiography. AJR Am J Roentgenol. 2010; 194(6):1590-1595. Observational-Dx 25 patients To compare the accuracy of visual grading of stenoses after plaque removal with visual grading in standard reconstructions. DSA was used as a reference standard. The average postprocessing time was 45 seconds. After plaque removal, all 25 relevant and 4 nonrelevant stenoses were correctly detected. Six relevant stenoses were overestimated as complete occlusions. With the standard reconstructions, two nonrelevant stenoses were overestimated as relevant. Correlation coefficients (r(2)) for the grading of stenoses after plaque removal and with standard reconstructions vs DSA were 0.7694 and 0.4329, respectively. Vessel contrast enhancement correlated weakly (r(2) = 0.2072) with the accuracy of plaque removal. Dual-energy CT with plaque removal automatically delivers CT luminograms with a high sensitivity for the detection of relevant stenoses and a higher correlation to DSA than standard reconstructions but frequently leads to an overestimation of high-grade stenoses as occlusions. Thus, dual-energy CT plaque and bone removal should be used complementary to standard reconstructions, and not exclusively. 2
47. Tang TY, Howarth SP, Miller SR, et al. The ATHEROMA (Atorvastatin Therapy: Effects on Reduction of Macrophage Activity) Study. Evaluation using ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging in carotid disease. J Am Coll Cardiol. 2009;53(22):2039-2050. Experimental-Tx 20 patients To evaluate the effects of low-dose (10 mg) and high-dose (80 mg) atorvastatin on carotid plaque inflammation as determined by ultrasmall superparamagnetic iron oxide (USPIO)-enhanced carotid magnetic resonance imaging (MRI). Twenty patients completed 12 weeks of treatment in each group. A significant reduction from baseline in USPIO-defined inflammation was observed in the 80-mg group at both 6 weeks (DeltaSI 0.13; p = 0.0003) and at 12 weeks (DeltaSI 0.20; p < 0.0001). No difference was observed with the low-dose regimen. The 80-mg atorvastatin dose significantly reduced total cholesterol by 15% (p = 0.0003) and low-density lipoprotein cholesterol by 29% (p = 0.0001) at 12 weeks. 1
48. U-King-Im JM, Tang TY, Patterson A, et al. Characterisation of carotid atheroma in symptomatic and asymptomatic patients using high resolution MRI. J Neurol Neurosurg Psychiatry. 2008;79(8):905-912. Observational-Dx 20 symptomatic and 20 asymptomatic patients To prospectively evaluate differences in carotid plaque characteristics in symptomatic and asymptomatic patients using high resolution MRI. After exclusion of poor quality images, 109 MRI sections in 18 symptomatic and 19 asymptomatic patients were available for analysis. There were no significant differences in mean luminal stenosis severity (72.9% vs 67.6%; p = 0.09) or plaque burden (median plaque areas 50 mm(2) vs 50 mm(2); p = 0.858) between the symptomatic and asymptomatic groups. However, symptomatic lesions had a higher incidence of ruptured fibrous caps (36.5% vs 8.7%; p = 0.004), haemorrhage or thrombus (46.5% vs 14.0%; p<0.001), large necrotic lipid cores (63.8% vs 28.0%; p = 0.002) and complicated type VI AHA lesions (61.5% vs 28.1%; p = 0.001) compared with asymptomatic lesions. The MRI findings of plaque haemorrhage or thrombus had an odds ratio of 5.25 (95% CI 2.08 to 13.24) while thin or ruptured fibrous cap (as opposed to a thick fibrous cap) had an odds ratio of 7.94 (95% CI 2.93 to 21.51) for prediction of symptomatic clinical status. 2
49. Wintermark M, Jawadi SS, Rapp JH, et al. High-resolution CT imaging of carotid artery atherosclerotic plaques. AJNR Am J Neuroradiol. 2008;29(5):875-882. Observational-Dx 8 patients To evaluate the ability of multidetector-row CT angiography (CTA) to assess the composition and characteristics of carotid artery atherosclerotic plaques with use of histologic examination as the gold standard. There was a 72.6% agreement between CTA and histologic examination in carotid plaque characterization. CTA showed perfect concordance for calcifications. A significant overlap between densities associated with lipid-rich necrotic core, connective tissue, and hemorrhage limited the reliability of individual pixel readings to identify these components. However, CTA showed good correlation with histologic examination for large lipid cores (kappa = 0.796; P < .001) and large hemorrhages (kappa = 0.712; P = .102). CTA performed well in detecting ulcerations (kappa = 0.855) and in measuring the fibrous cap thickness (R(2) = 0.77; P < .001). 2
50. Chen A, Shyr MH, Chen TY, Lai HY, Lin CC, Yen PS. Dynamic CT perfusion imaging with acetazolamide challenge for evaluation of patients with unilateral cerebrovascular steno-occlusive disease. AJNR Am J Neuroradiol. 2006;27(9):1876-1881. Observational-Dx 15 patients To assess cerebral hemodynamics by using these parameters and acetazolamide challenge in patients with cerebrovascular steno-occlusive disease. Significant decreases in CBF (-25.1%, P = .003) and significant increases in MTT (47.1%, P < .001) were found in stenotic hemispheres. After acetazolamide challenge, significant changes in CBF (-39.5%, P < .001) and MTT (92.9%, P < .001) were also seen. The acetazolamide test significantly decreased CBF hemispheric ratio (-20.3%, P < .001) and increased MTT hemispheric ratio (30.8%, P = .002), making both maps more asymmetric. Significance in CBF and MTT percent changes (P < .001 and P = .005, respectively) was found between hemispheres. When CBF percent changes were assumed to represent the true determinant of hemodynamic impairment, normal ranges of baseline MTT value and MTT percent changes demonstrated sensitivities of 66.7% and 100% and specificities of 58.3% and 75%, respectively, for detecting patients with hemodynamic impairment. 4
51. Endo H, Inoue T, Ogasawara K, Fukuda T, Kanbara Y, Ogawa A. Quantitative assessment of cerebral hemodynamics using perfusion-weighted MRI in patients with major cerebral artery occlusive disease: comparison with positron emission tomography. Stroke. 2006;37(2):388-392 Observational-Dx 29 total patients To validate the accuracy of PW MRI for detecting hemodynamic impairment by correlating CBV measured by PW MRI with CVR measured by PET in patients with unilateral major cerebral artery occlusive disease. A significant negative correlation was observed between PW MRI-CBV and PET-CVR (r=-0.713; P<0.0001). PW MRI-CBV higher than the mean +2 SD obtained in normal subjects (15.2 mL/100 g) was defined as elevated and PET-CVR lower than the mean -2 SD obtained in normal subjects (15.1%) was defined as reduced. Assuming the PET-CVR as the true determinant of hemodynamic impairment, PW MRI-CBV provided 80.0% sensitivity and 91.7% specificity, with 80.0% positive predictive value for detecting patients with reduced CVR. 3
52. Menon BK, Puetz V, Kochar P, Demchuk AM. ASPECTS and other neuroimaging scores in the triage and prediction of outcome in acute stroke patients. Neuroimaging Clin N Am. 2011;21(2):407-423, xii. Review/Other-Dx N/A To summarize ASPECTS and other neuroimaging scores developed for risk prognostication and risk stratification with treatment in patients with acute ischemic stroke. Neuroimaging scores such as ASPECTS, CBS, leptomeningeal collateral score, pc-ASPECTS, and BASIS help in conveying pathophysiological information in acute ischemic strokes derivedfrom imaging techniques in a simple, easy to use form that helps clinicians in making appropriate treatment decisions and in determining prognosis with reasonable accuracy. These scores alsohelp in creating an easily understandable numerical scale for use in acute ischemic stroke trials. It is, however, imperative that treating physicians understand the limitations of these scales and use them in the appropriate clinical context when making decisions that affect patient management. 4
53. Vora NA, Gupta R, Thomas AJ, et al. Factors predicting hemorrhagic complications after multimodal reperfusion therapy for acute ischemic stroke. AJNR Am J Neuroradiol. 2007;28(7):1391-1394. Observational-Tx 185 patients To find predictors for hemorrhagic complications in patients with acute ischemic stroke treated with multimodal endovascular therapy. Sixty-nine patients (37%) developed postprocedural hemorrhages: 24 (13%) parenchymal hematomas and 45 (24%) hemorrhagic infarctions. Patients with tandem occlusions (odds ratio [OR] 4.6 [1.4-6.5], P<.016), hyperglycemia (OR 2.8 [1.1-7.7], P<.043), or treated concomitantly with intravenous (IV) tissue plasminogen activator (tPA) and intra-arterial (IA) urokinase (OR 5.1 [1.1-25.0], P<.041) were at a significant risk for a parenchymal hematoma. Hemorrhagic infarction occurred significantly more in patients presenting with an ASPECTS<or=7 (OR 1.9 [1.3-2.7], P<.01). 2
54. Saqqur M, Uchino K, Demchuk AM, et al. Site of arterial occlusion identified by transcranial Doppler predicts the response to intravenous thrombolysis for stroke. Stroke. 2007;38(3):948-954. Observational-Dx 335 patients To examine clinical outcomes and recanalization rates in a multicenter cohort of stroke patients receiving intravenous tissue plasminogen activator by site of occlusion localized with bedside transcranial Doppler. Three hundred thirty-five patients had a mean age 69+/-13 years and 48.5% were women (median baseline National Institutes of Health Stroke Scale score 16 [range, 3 to 32], mean time to transcranial Doppler 140+/-84 minutes, and mean time to intravenous tissue plasminogen activator 145+/-68 minutes). Distal middle cerebral artery occlusion had an OR of 2 for complete recanalization (50 of 113 [44.2%], 95% CI: 1.1 to 3.1, P=0.005), proximal middle cerebral artery 0.7 (49 of 163 [30%], 95% CI: 0.4 to 1.1, P=0.13), terminal internal carotid artery 0.1 (one of 17 [5.9%], 95% CI: 0.015 to 0.8, P=0.015), tandem cervical internal carotid artery/middle cerebral artery 0.7 (6 of 22 [27%], 95% CI: 0.3 to 1.9, P=0.5), and basilar artery 0.96 (3 of 10 [30%], 95% CI: 0.2 to 4, P=0.9). Prerecombinant tissue plasminogen activator National Institutes of Health Stroke Scale score, systolic blood pressure, glucose, and Thrombolysis in Brain Ischemia flow grade at the occlusion site were the negative independent predictors for complete recanalization in the final model. There were no associations among time to treatment, stroke mechanisms, or recanalization rate. Patients with no flow (Thrombolysis in Brain Ischemia 0) at the occlusion site had less probability of complete recanalization than patients with dampened flow (Thrombolysis in Brain Ischemia 3) (OR(adj): 0.256, 95% CI: 0.11 to 0.595, P=0.002). Continuous transcranial Doppler monitoring (exposure to ultrasound) was a positive predictor for complete recanalization (OR(adj): 3.02, 95% CI: 1.396 to 6.514, P=0.005). National Institutes of Health Stroke Scale score < or =2 at 24 hours was achieved in 66 of 305 patients (22%): distal middle cerebral artery 33% (35 of 107), tandem cervical internal carotid artery/middle cerebral artery 24% (5 of 21), proximal middle cerebral artery 16% (24 of 155), basilar artery 25% (2 of 8), and none of the patients with terminal internal carotid artery had dramatic recovery (0%, n=14; P=0.003). Modified Rankin Scale score < or =1 was achieved in 90 of 260 patients (35%): distal middle cerebral artery 52% (50 of 96), proximal middle cerebral artery 25% (33 of 131), tandem cervical internal carotid artery/middle cerebral artery 21% (3 of 14), terminal internal carotid artery 18% (2 of 11), and basilar artery 25% (2 of 8) (P<0.001). Patients with distal middle cerebral artery occlusion were twice as likely to have a good long-term outcome as patients with proximal middle cerebral artery (OR: 2.1, 95% CI: 1.1 to 4, P=0.025). 4
55. Dani KA, Thomas RG, Chappell FM, et al. Computed tomography and magnetic resonance perfusion imaging in ischemic stroke: definitions and thresholds. Ann Neurol. 2011;70(3):384-401. Review/Other-Dx 69 papers To systematically reviewed CT and MR perfusion imaging in acute ischemic stroke. Among 7,152 papers, 69 met inclusion criteria for analysis of definitions (49 MR and 20 CT), 21 MR (n = 551), and 10 CT (n = 266) papers, median sample size 22, provided thresholds. We found multiple definitions for tissue states, eg, tissue at risk, 18; nonviable tissue, 12; 16, no definition. Perfusion parameters varied widely; eg, 9 different MR, 6 different CT parameters for the "at risk"/"not at risk threshold." Median threshold values varied up to 4-fold, eg, for the "at risk"/"not at risk threshold," median cerebral blood flow ranged from 18 to 37ml/100g/min; mean transit time from 1.8 to 8.3 seconds relative to the contralateral side. The influence of reperfusion and duration of ischemia could not be assessed. 4
56. Deipolyi AR, Wu O, Macklin EA, et al. Reliability of cerebral blood volume maps as a substitute for diffusion-weighted imaging in acute ischemic stroke. J Magn Reson Imaging. 2012;36(5):1083-1087. Observational-Dx 58 patients To assess the reliability of cerebral blood volume (CBV) maps as a substitute for diffusion-weighted MRI (DWI) in acute ischemic stroke. Using the full scan duration (110 s), rrCBV was increased in most DWI lesions (62%; 95% confidence interval, 48-74%). rrCBV increased with increasing scan duration (P < 0.001). Even with the shortest duration (39.5 s) rrCBV was increased in 33% of lesions. 4
57. Fahmi F, Marquering HA, Streekstra GJ, et al. Differences in CT perfusion summary maps for patients with acute ischemic stroke generated by 2 software packages. AJNR Am J Neuroradiol. 2012;33(11):2074-2080. Observational-Dx 26 consecutive patients To assess the variability of the area of infarct core and penumbra as presented in summary maps produced by 2 different software packages. There was a statistically significant difference in infarct core area (-23.6 +/- 25.6 cm(2)) and penumbra area (15.8 +/- 25.3 cm(2)) between the 2 software packages. For all the areas presented in the summary maps, the Bland-Altman interval limit of agreement was larger than 100 cm(2). 2
58. Gonzalez RG.. Low signal, high noise and large uncertainty make CT perfusion unsuitable for acute ischemic stroke patient selection for endovascular therapy. J Neurointerv Surg. 4(4):242-5, 2012 Jul. Review/Other-Dx N/A To review the evidence that led to my current view on the best practices for imaging the stroke patient. No results stated in abstract. 4
59. Gonzalez RG, Copen WA, Schaefer PW, et al. The Massachusetts General Hospital acute stroke imaging algorithm: an experience and evidence based approach. J Neurointerv Surg. 2013;5 Suppl 1:i7-12. Review/Other-Dx N/A To use an experience and evidence based approach to develop the neuroimaging algorithm that best improves outcomes in patients with severe ischemic strokes caused by anterior circulation occlusions (ACOs). The Massachusetts General Hospital Neuroradiology Division employed an experience and evidence based approach to develop a neuroimaging algorithm to best select patients with severe ischemic strokes caused by anterior circulation occlusions (ACOs) for intravenous tissue plasminogen activator and endovascular treatment. Methods found to be of value included the National Institutes of Health Stroke Scale (NIHSS), non-contrast CT, CT angiography (CTA) and diffusion MRI. Perfusion imaging by CT and MRI were found to be unnecessary for safe and effective triage of patients with severe ACOs. An algorithm was adopted that includes: non-contrast CT to identify hemorrhage and large hypodensity followed by CTA to identify the ACO; diffusion MRI to estimate the core infarct; and NIHSS in conjunction with diffusion data to estimate the clinical penumbra. 4
60. Kamalian S, Maas MB, Goldmacher GV, et al. CT cerebral blood flow maps optimally correlate with admission diffusion-weighted imaging in acute stroke but thresholds vary by postprocessing platform. Stroke. 2011;42(7):1923-1928. Observational-Dx 48 consecutive cases (1) determine the optimal CT perfusion parameter to define infarct core using various postprocessing platforms; and (2) establish the degree of variability in threshold values between these different platforms. Cerebral blood flow had the highest accuracy (receiver operating characteristic area under the curve) for all 3 platforms (P<0.01). The maximal areas under the curve for each parameter were: absolute cerebral blood flow 0.88, cerebral blood volume 0.81, and mean transit time 0.82 and relative Cerebral blood flow 0.88, cerebral blood volume 0.83, and mean transit time 0.82. Optimal receiver operating characteristic operating point thresholds varied significantly between different platforms (Friedman test, P<0.01). 3
61. Konstas AA, Goldmakher GV, Lee TY, Lev MH. Theoretic basis and technical implementations of CT perfusion in acute ischemic stroke, part 2: technical implementations. AJNR Am J Neuroradiol. 2009;30(5):885-892. Review/Other-Dx N/A To highlight the need for validation and standardization of important CTP parameters to improve patient outcomes and design future randomized clinical trialsthat will provide evidence for the importance of the core/penumbra “mismatch” in patient triage for recanalization therapies beyond the current 3-hour therapeutic window for intravenous thrombolysis. CT perfusion (CTP) is a functional imaging technique that provides important information about capillary-level hemodynamics of the brain parenchyma and is a natural complement to the strengths of unenhanced CT and CT angiography in the evaluation of acute stroke, vasospasm, and other neurovascular disorders. CTP is critical in determining the extent of irreversibly infarcted brain tissue (infarct "core") and the severely ischemic but potentially salvageable tissue ("penumbra"). This is achieved by generating parametric maps of cerebral blood flow, cerebral blood volume, and mean transit time. 4
62. Cheng AL, Batool S, McCreary CR, et al. Susceptibility-weighted imaging is more reliable than T2*-weighted gradient-recalled echo MRI for detecting microbleeds. Stroke. 2013;44(10):2782-2786. Observational-Dx 9 patients and 21 controls To investigate the sensitivity and reliability of MRI susceptibility-weighted imaging (SWI) compared with routine MRI T2*-weighted gradient-recalled echo (GRE) for cerebral microbleed (CMB) detection. In 9 cerebral amyloid angiopathy cases, the raters identified 1146 total CMBs on GRE and 1432 CMBs on SWI. In 22 healthy control subjects, the raters identified >/=1 CMBs in 6/22 on GRE (total 9 CMBs) and 5/22 on SWI (total 19 CMBs). Among cerebral amyloid angiopathy cases, the reliability between raters for CMB counts was good for SWI (intraclass correlation coefficient, 0.87) but only moderate for GRE (intraclass correlation coefficient, 0.52). In controls, agreement on the presence or absence of CMBs in controls was moderate to good on both SWI (kappa coefficient ranged from 0.57 to 0.74 across the 3 combinations of rater pairs) and GRE (kappa range, 0.31 to 0.70). A review of 114 hypointensities identified as possible CMBs indicated that increased detection and reliability on SWI was related to both increased contrast and higher resolution, allowing better discrimination of CMBs from the background and better anatomic differentiation from pial vessels. 2
63. Verma RK, Kottke R, Andereggen L, et al. Detecting subarachnoid hemorrhage: comparison of combined FLAIR/SWI versus CT. Eur J Radiol. 2013;82(9):1539-1545. Observational-Dx 25 patients To compare the utility of susceptibility weighted imaging (SWI) with the established diagnostic techniques CT and fluid attenuated inversion recovery (FLAIR) in their detecting capacity of subarachnoid hemorrhage (SAH), and further to compare the combined SWI/FLAIR MRI data with CT to evaluate whether MRI is more accurate than CT. SAH was detected in a total of 146 subarachnoid regions. CT identified 110 (75.3%), FLAIR 127 (87%), and SWI 129 (88.4%) involved regions. Combined FLAIR and SWI identified all 146 detectable regions (100%). FLAIR was sensitive for frontal-parietal, temporal-occipital and Sylvian cistern SAH, while SWI was particularly sensitive for interhemispheric and intraventricular hemorrhage. 2
64. Lansberg MG, Straka M, Kemp S, et al. MRI profile and response to endovascular reperfusion after stroke (DEFUSE 2): a prospective cohort study. Lancet Neurol. 2012;11(10):860-867. Review/Other-Dx 138 patients To establish whether MRI can be used to identify patients who are most likely to benefit from endovascular reperfusion. 138 patients were enrolled. 110 patients had catheter angiography and of these 104 had an MRI profile and 99 could be assessed for reperfusion. 46 of 78 (59%) patients with target mismatch and 12 of 21 (57%) patients without target mismatch had reperfusion after endovascular treatment. The adjusted odds ratio (OR) for favourable clinical response associated with reperfusion was 8.8 (95% CI 2.7-29.0) in the target mismatch group and 0.2 (0.0-1.6) in the no target mismatch group (p=0.003 for difference between ORs). Reperfusion was associated with increased good functional outcome at 90 days (OR 4.0, 95% CI 1.3-12.2) in the target mismatch group, but not in the no target mismatch group (1.9, 0.2-18.7). 4
65. Yoo AJ, Verduzco LA, Schaefer PW, Hirsch JA, Rabinov JD, Gonzalez RG. MRI-based selection for intra-arterial stroke therapy: value of pretreatment diffusion-weighted imaging lesion volume in selecting patients with acute stroke who will benefit from early recanalization. Stroke. 2009;40(6):2046-2054. Observational-Dx 34 consecutive patients To determine if this threshold could identify patients treated with intra-arterial therapy who would do poorly despite reperfusion. Among patients with initial infarcts >70 cm(3), all had poor outcomes despite a 50% recanalization rate with mean infarct growth of 114 cm(3). These patients also had the largest mean transit time volumes (P<0.04). Patients with initial infarct volumes <70 cm(3) who recanalized early had the best clinical outcomes (P<0.008) with a 64% rate of modified Rankin Scale score <or=2 and the least infarct growth (P<0.03) with mean growth of 18 cm(3). 3
66. Sanak D, Nosal V, Horak D, et al. Impact of diffusion-weighted MRI-measured initial cerebral infarction volume on clinical outcome in acute stroke patients with middle cerebral artery occlusion treated by thrombolysis. Neuroradiology. 2006;48(9):632-639. Observational-Dx 25 consecutive CI patients To assess the correlation between initial cerebral infarct (CI) volume (quantified on diffusion-weighted MRI) and the resulting clinical outcome in acute stroke patients with middle cerebral artery (MCA) (M(1-2) segment) occlusion detected on MRI angiography treated by intravenous/intraarterial thrombolysis. V(DWI-I) ranged from 0.7 to 321 ml. The 24-h clinical outcome improved significantly (P=0.0001) in 87% of patients with a V(DWI-I) < or =70 ml (group 1) and deteriorated significantly (P=0.0018) in all patients with a V(DWI-I) >70 ml (group 2). The 90-day mortality was 0% in group 1 and 71.5% in group 2. The 90-day clinical outcome was significantly better in group 1 than in group 2 (P=0.026). 3
67. Riedel CH, Zimmermann P, Jensen-Kondering U, Stingele R, Deuschl G, Jansen O. The importance of size: successful recanalization by intravenous thrombolysis in acute anterior stroke depends on thrombus length. Stroke. 2011;42(6):1775-1777. Observational-Dx 138 patients To investigate if thrombus lengths, measured in thin-slice nonenhanced CT images, can be used to predict the likelihood of a successful recanalization by IVT. In 62 patients, IVT resulted in recanalization; among these patients, no thrombus length exceeded 8 mm. The median modified Rankin scale score at hospital discharge was 2. In the remaining 76 patients, thrombus lengths mostly exceeded 8 mm and IVT failed in recanalization. These patients were discharged with a median modified Rankin scale score of 5. 4
68. Furlan AJ, Eyding D, Albers GW, et al. Dose Escalation of Desmoteplase for Acute Ischemic Stroke (DEDAS): evidence of safety and efficacy 3 to 9 hours after stroke onset. Stroke 2006;37:1227-31. Experimental-Tx 37 patients To evaluate safety and efficacy of intravenous (IV) desmoteplase in patients with perfusion/diffusion mismatch on MRI 3 to 9 hours after onset of acute ischemic stroke. Thirty-seven patients were randomized and received treatment (intent-to-treat; placebo: n=8; 90 microg/kg: n=14; 125 microg/kg: n=15). No symptomatic intracranial hemorrhage occurred. Reperfusion was achieved in 37.5% (95% CI [8.5; 75.5]) of placebo patients, 18.2% (2.3; 51.8) of patients treated with 90 microg/kg desmoteplase, and 53.3% (26.6; 78.7) of patients treated with 125 microg/kg desmoteplase. Good clinical outcome at 90 days occurred in 25.0% (3.2; 65.1) treated with placebo, 28.6% (8.4; 58.1) treated with 90 microg/kg desmoteplase and 60.0% (32.3; 83.7) treated with 125 microg/kg desmoteplase. In the target population (n=25), the difference compared with placebo increased and was statistically significant for good clinical outcome with 125 microg/kg desmoteplase (P=0.022). 1
69. Hacke W, Albers G, Al-Rawi Y, et al. The Desmoteplase in Acute Ischemic Stroke Trial (DIAS): a phase II MRI-based 9-hour window acute stroke thrombolysis trial with intravenous desmoteplase. Stroke. 2005;36(1):66-73. Experimental-Tx 104 patients To evaluate the safety and efficacy of intravenous desmoteplase, a highly fibrin-specific and nonneurotoxic thrombolytic agent, administered within 3 to 9 hours of ischemic stroke onset in patients with perfusion/diffusion mismatch on MRI. Part 1 was terminated prematurely because of high rates of sICH with desmoteplase (26.7%). In Part 2, the sICH rate was 2.2%. No sICH occurred with placebo in either part. Reperfusion rates up to 71.4% (P=0.0012) were observed with desmoteplase (125 microg/kg) compared with 19.2% with placebo. Favorable 90-day clinical outcome was found in 22.2% of placebo-treated patients and between 13.3% (62.5 microg/kg; P=0.757) and 60.0% (125 microg/kg; P=0.0090) of desmoteplase-treated patients. Early reperfusion correlated favorably with clinical outcome (P=0.0028). Favorable outcome occurred in 52.5% of patients experiencing reperfusion versus 24.6% of patients without reperfusion. 1
70. Gonzalez RG. Current state of acute stroke imaging. Stroke. 2013;44(11):3260-3264. Review/Other-Dx N/A To review the rapid diagnosis of acute stroke, the guidance of treatment using intravenously administered tissue-type plasminogen activator (tPA), and intra-arterial treatments (IATs). CT and MRI of the patients with acute ischemic stroke provide valuable diagnostic and prognostic information. Neuroimaging can inform on the presence of hemorrhage, vessel occlusion, irreversible injury, and tissue at risk, which helps in making optimal patient management decisions. CT and MRI provide complementary information, and the most comprehensive understanding of the state of the brain in the patient with a stroke syndrome may require both. Much progress has been made in treating stroke, and new insights on stroke physiology provided by imaging suggest that there are major opportunities to treat many more patients effectively. 4
71. Donnan GA, Baron JC, Ma H, Davis SM. Penumbral selection of patients for trials of acute stroke therapy. Lancet Neurol. 2009;8(3):261-269. Review/Other-Dx N/A To discuss the background of penumbral selection for therapy, the current status of this approach for several interventions, and areas of future research. Imaging of the ischaemic penumbra is a promising approach to the selection of patients with acute ischaemic stroke for trials of intervention at more than 3 h after onset. Several advances facilitate online assessment of patients for mismatch volumes to improve selection for clinical trials. Furthermore, large mismatch volumes determined with stricter perfusion criteria than the currently used 20% might be required to recruit the most therapeutically responsive patients. To extend the therapeutic time window beyond 3–4·5 h for alteplase, particularly for times up to 9–12 h, more phase III randomised, controlled trials that use penumbral selection are needed. 4
72. Jovin TG, Liebeskind DS, Gupta R, et al. Imaging-based endovascular therapy for acute ischemic stroke due to proximal intracranial anterior circulation occlusion treated beyond 8 hours from time last seen well: retrospective multicenter analysis of 237 consecutive patients. Stroke. 42(8):2206-11, 2011 Aug. Observational-Dx 237 patients To assess safety, procedural, and clinical outcomes of MRI or CT perfusion imaging-based endovascular therapy in patients with anterior circulation stroke treated beyond 8 hours from time last seen well. Two hundred thirty-seven patients were identified (mean age, 63.8 +/- 16 years; mean baseline National Institutes of Health Stroke Scale, 15 +/- 5.5; mean time last seen well to treatment, 15 +/- 11.2 hours; male gender, 46%). Successful revascularization was achieved in 175 of 237 (73.84%) patients. Parenchymal hematoma occurred in 21 of 237 (8.86%) patients. The 90-day mortality rate was 21.5% (51 of 237). The rate of good outcomes was 45% (100 of 223) in the 223 patients with available modified Rankin Scale data at 90 days or time of hospital discharge. In multivariate analyses, age (OR, 0.96; 95% CI, 0.94 to 0.98; P=0.002), admission National Institutes of Health Stroke Scale (OR, 0.93; 0.87 to 0.98; P=0.016), and successful revascularization (OR, 4.32; 1.99 to 9.39; P<0.0001) were identified as independent predictors of good outcomes. 3
73. Kim JT, Yoon W, Park MS, et al. Early outcome of combined thrombolysis based on the mismatch on perfusion CT. Cerebrovasc Dis. 2009;28(3):259-265. Review/Other-Dx 18 patients To assess whether combined intravenous (IV) and intra-arterial (IA) thrombolysis performed according to the status of tissue based on perfusion computed tomography (PCT) is beneficial for the early outcome in patients with acute ischemic stroke. Eighteen patients (11 men) underwent combined IV/IA thrombolysis. The recanalization rate after combined IV/IA thrombolysis was 88.9% (TIMI 2, 4; TIMI 3, 12). A good functional outcome at discharge was noted in 12 patients (66.7%). The incidence of symptomatic intracranial hemorrhage was 5.6% (1/18). 4
74. Michel P, Ntaios G, Reichhart M, et al. Perfusion-CT guided intravenous thrombolysis in patients with unknown-onset stroke: a randomized, double-blind, placebo-controlled, pilot feasibility trial. Neuroradiology. 2012;54(6):579-588. Experimental-Tx 12 patients To design a pilot study to assess feasibility of a trial of perfusion computed tomography (PCT)-guided thrombolysis in patients with ischemic tissue at risk of infarction and unknown stroke onset. At baseline, there was a trend towards older age [69.5 (57-78) vs. 49 (44-78) years] in the thrombolysis group (n = 6) compared to placebo (n = 6). Regarding feasibility, hospital arrival to treatment delay was above the allowed 2 h in three patients (25%). There were two protocol violations (17%) regarding PCT, both underestimating the predicted infarct in patients randomized in the placebo group. No symptomatic hemorrhage or death occurred during the first 7 days. Three of the four (75%) and one of the five (20%) patients were recanalized in the thrombolysis and placebo group respectively. The volume of non-infarcted at-risk tissue was 84 (44-206) cm(3) in the treatment arm and 29 (8-105) cm(3) in the placebo arm. 1
75. Delgado Almandoz JE, Yoo AJ, Stone MJ, et al. The spot sign score in primary intracerebral hemorrhage identifies patients at highest risk of in-hospital mortality and poor outcome among survivors. Stroke. 2010;41(1):54-60. Observational-Dx 573 consecutive patients; 3 reviewers Retrospective study to assess whether the spot sign score can be used to identify primary ICH patients who are at highest risk of in-hospital mortality and poor outcome among survivors at 3-month follow-up. Spot signs identified in 133/573 CT angiograms (23.2%), 11 of which were delayed spot signs (8.3%). The presence of any spot sign increased the risk of in-hospital mortality (55.6%, OR 4.0, 95% CI, 2.6 to 5.9, P<0.0001) and poor outcome among survivors at 3-month follow-up (50.8%, OR 2.5, 95% CI, 1.4 to 4.3, P<0.0014). Spot sign score successfully predicted an escalating risk of both outcome measures. In multivariate analysis, the spot sign score was an independent predictor of in-hospital mortality (OR 1.5, 95% CI, 1.2 to 1.9, P<0.0002) and poor outcome among survivors at 3-month follow-up (OR 1.6, 95% CI, 1.1 to 2.1, P<0.0065). The spot sign score is an independent predictor of in-hospital mortality and poor outcome among survivors in primary ICH. 3
76. Wada R, Aviv RI, Fox AJ, et al. CT angiography "spot sign" predicts hematoma expansion in acute intracerebral hemorrhage. Stroke. 2007;38(4):1257-1262. Observational-Dx 39 patients To assess whether the CTA finding of tiny, enhancing foci (the “spot sign” ) within hematomas is associated with hematoma expansion and poor clinical outcomes. Thirteen patients (33%) demonstrated 31 enhancing foci. Baseline clinical variables were similar in both groups. Hematoma expansion occurred in 11 patients (28%) on follow-up. Seventy-seven percent of patients with and 4% without hematoma expansion demonstrated the spot sign (P<0.0001). Sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio for expansion were 91%, 89%, 77%, 96%, and 8.5, respectively. Interobserver agreement was high (kappa=0.92 to 0.94). In patients with the spot sign, mean volume change was greater (P=0.008), extravasation more common (P=0.0005), and median hospital stay longer (P=0.04), and fewer patients achieved a good outcome (modified Rankin Scale score <2), although the latter was not significant (P=0.16). No differences in hydrocephalus (P=1.00), surgical intervention (P=1.00), or death (P=0.60) were noted between groups. In multiple regression, the spot sign independently predicted hematoma expansion (P=0.0003). 3
77. Lee C, Pennington MA, Kenney CM, 3rd. MR evaluation of developmental venous anomalies: medullary venous anatomy of venous angiomas. AJNR Am J Neuroradiol. 1996;17(1):61-70. Review/Other-Dx 61 patients To present characteristic MR findings of developmental venous anomalies (DVAs) in terms of location of caput and draining veins, to correlate these findings with normal medullary venous anatomy, and to suggest an approach to the evaluation of DVAs by means of MR imaging. Seventy-two DVAs with 78 draining veins were located: 18 were juxtacortical, 13 were subcortical, and 41 were periventricular or deep. Twenty-six of the DVA caputs were frontal, 16 were parietal, 13 were in the brachium pontis/dentate, seven were in the temporal lobe, three were in the cerebellar hemisphere, three were in the occipital lobe, three were in the basal ganglia, and one was in the pons. The draining veins were superficial in 29 cases and deep in 49. Of the 36 supratentorial deep draining veins, 16 were in the trigone/occipital horn, 11 were in the mid-body of the lateral ventricle, seven were in the frontal horn, and two were in the temporal horn. Among the 14 infratentorial deep draining veins, five were in the lateral recess of the fourth ventricle, four were anterior transpontine veins, three were lateral transpontine veins, and two were precentral cerebellar veins. 4
78. Ruiz DS, Yilmaz H, Gailloud P. Cerebral developmental venous anomalies: current concepts. Ann Neurol. 2009;66(3):271-283. Review/Other-Dx N/A To review current concepts on DVAs with the aim of helping clinicians understand this complex entity. Cerebral developmental venous anomalies are the most frequently encountered cerebral vascular malformation, and as such, are frequently reported as fortuitous findings in computed tomography (CT) and magnetic resonance imaging (MRI) studies. Developmental venous anomalies (DVAs) are generally considered extreme anatomical variations of the cerebral vasculature, and follow a benign clinical course in the vast majority of cases. 4
79. Santucci GM, Leach JL, Ying J, Leach SD, Tomsick TA. Brain parenchymal signal abnormalities associated with developmental venous anomalies: detailed MR imaging assessment. AJNR Am J Neuroradiol. 2008;29(7):1317-1323. Observational-Dx 164 patients To evaluate the prevalence of brain parenchymal signal-intensity abnormalities subjacent to DVA, correlating with DVA morphology and location. Of the 175 DVAs identified, 28 had associated signal-intensity abnormalities in the drainage territory. Seven of 28 DVAs with signal-intensity abnormalities were excluded because of significant adjacent white matter signal-intensity changes related to other pathology overlapping the drainage territory. Of the remaining DVAs imaged in this study, 21/168 (12.5%) had subjacent signal-intensity abnormalities. An adjusted prevalence rate of 9/115 (7.8%) was obtained by excluding patients with white matter disease more than minimal in degree. Periventricular location and older age were associated with DVA signal-intensity abnormality. 3
80. Campbell PG, Jabbour P, Yadla S, Awad IA. Emerging clinical imaging techniques for cerebral cavernous malformations: a systematic review. Neurosurg Focus. 2010;29(3):E6. Review/Other-Dx N/A To provide a concise review of the emerging imaging methods used in the clinical diagnosis and treatment of CCMs. Prior to the advent of MRI, evaluation of CCMs was limited to diagnostic angiography and CT. Currently, MR imaging is the best imaging method to evaluate CCMs, with T2*GRE sequences being described as the “gold standard.”10,30,54 As the use of more advanced imaging techniques continues to achieve widespread distribution, high-field MR imaging and SW MR imaging are likely to become commonplace for the diagnosis and follow-up of these lesions. Additionally, applications such as DT imaging and fMR imaging may achieve more relevance as intraoperative navigational modalities for deep-seated lesions in eloquent areas. 4
81. Smith ER, Scott RM. Cavernous malformations. Neurosurg Clin N Am. 2010;21(3):483-490. Review/Other-Dx N/A To discuss the epidemiology, natural history, diagnosis, treatment and follow-up of children who are found to harbor these lesions. The management of children with CMs requires a clear understanding of the natural history of these lesions and the risks of surgical intervention. Presentation is usually hemorrhage, seizure, focal neurologic deficit, or headache. Diagnosis is best made with MRI. Patients with multiple lesions should be referred for genetic evaluation and counseling. Individuals with symptomatic, growing, or hemorrhagic malformations should be considered for surgical resection. Close follow-up after diagnosis and treatment is helpful to identify lesion progression or recurrence. 4
82. Thomas B, Somasundaram S, Thamburaj K, et al. Clinical applications of susceptibility weighted MR imaging of the brain - a pictorial review. Neuroradiology. 2008;50(2):105-116. Review/Other-Dx N/A A pictorial review covering many clinical conditions illustrating its usefulness. The phase images are useful in differentiating between diamagnetic and paramagnetic susceptibility effects of calcium and blood, respectively. This unique MR sequence will help in detecting occult low flow vascular lesions, calcification and cerebral microbleed in various pathologic conditions and aids in characterizing tumors and degenerative diseases of the brain. This sequence also can be used to visualize normal brain structures with conspicuity. 4
83. Jagadeesan BD, Delgado Almandoz JE, Moran CJ, Benzinger TL. Accuracy of susceptibility-weighted imaging for the detection of arteriovenous shunting in vascular malformations of the brain. Stroke. 2011;42(1):87-92. Observational-Dx 60 patients To determine the accuracy of susceptibility-weighted MRI (SWI) for the detection of arteriovenous shunting (AVS) in vascular malformations of the brain (BVM). A total of 80 BVM were identified in the 60 patients included in our study. Of the 29 BVM with AVS on digital subtraction angiography, 14 were untreated arteriovenous malformations, 10 were previously treated arteriovenous malformations, and 5 were untreated dural arteriovenous fistulas. Overall, SWI was 93% sensitive and 98% specific for the detection of AVS in BVM, with excellent interobserver agreement (kappa=0.94). In the 14 previously treated arteriovenous malformations, SWI was 100% sensitive and specific for the detection of AVS. In the 28 BVM associated with intracerebral hemorrhage, SWI was 100% sensitive and 96% specific for the detection of AVS. 3
84. Saposnik G, Barinagarrementeria F, Brown RD, Jr., et al. Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011;42:1158-92. Review/Other-Tx N/A To provide an overview of cerebral venous sinus thrombosis and to provide recommendations for its diagnosis, management, and treatment. No results stated in abstract 4
85. Ozsvath RR, Casey SO, Lustrin ES, Alberico RA, Hassankhani A, Patel M. Cerebral venography: comparison of CT and MR projection venography. AJR Am J Roentgenol 1997;169:1699-707. Observational-Dx 24 patients To show equivalence or superiority of CT venography compared with the existing test of choice--MR venography--in the evaluation of dural sinus thrombosis and in the identification of cerebral veins and dural sinuses. Using MR venography, the two radiologists diagnosed dural sinus thrombosis in eight of the 17 patients with suspected dural sinus thrombosis. In these eight patients, the diagnosis was also made with CT venography. The diagnosis was confirmed by follow-up CT in four patients and by follow-up MR imaging in two patients. The MIP algorithm did not allow direct visualization of thrombus by either the CT or the MR imaging technique; however, the CT integral display algorithm enabled direct visualization of thrombus on the three-dimensional projection venograms. The systematic comparison of imaging techniques showed that CT venography reliably reveals all cerebral veins and sinuses when they are seen with MR venography. In addition, CT venography more frequently visualizes sinuses or smaller cerebral veins with low flow as compared with MR venography. 3
86. Gupta RK, Bapuraj JR, Khandelwal N, Khurana D. Prognostic indices for cerebral venous thrombosis on CT perfusion: a prospective study. Eur J Radiol. 83(1):185-90, 2014 Jan. Observational-Dx 20 patients To determine the prognostic significance of CT perfusion characteristics of patients with cerebral venous sinus thrombosis (CVST) and assessed the change in perfusion parameters following anticoagulation therapy. All patients in this study showed areas of hypoperfusion on CT perfusion. To determine the favorable clinical outcome on basis of perfusion parameters, ROC curve analysis was performed which showed that the optimal threshold for rCBF>60.5%, rCBV>75.5%, and rMTT<148.5% correlated with better clinical outcomes. Post treatment perfusion parameters showed significant correlation in core of the lesion (p<0.05) than in the periphery. 3
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