Carotid Bulb Webs as a Cause of “Cryptogenic” Ischemic Stroke

BACKGROUND AND PURPOSE:Carotid webs are intraluminal shelf-like filling defects at the carotid bulb with recently recognized implications in patients with recurrent ischemic stroke. We sought to determine whether carotid webs are an under-recognized cause of “cryptogenic” ischemic stroke and to estimate their prevalence in the general population.MATERIALS AND METHODS:A retrospective review of neck CTA studies in young patients with cryptogenic stroke over the past 6 years (n = 33) was performed to determine the prevalence of carotid webs compared with a control group of patients who received neck CTA studies for reasons other than ischemic stroke (n = 63).RESULTS:The prevalence of carotid webs in the cryptogenic stroke population was 21.2% (95% CI, 8.9%–38.9%). Patients with symptomatic carotid webs had a mean age of 38.9 years (range, 30–48 years) and were mostly African American (86%) and women (86%). In contrast, only 1.6% (95% CI, 0%–8.5%) of patients in the control group demonstrated a web. Our findings demonstrate a statistically significant association between carotid webs and ischemic stroke (OR = 16.7; 95% CI, 2.78–320.3; P = .01).CONCLUSIONS:Carotid webs exhibit a strong association with ischemic stroke, and their presence should be suspected in patients lacking other risk factors, particularly African American women.

Carotid artery webs are shelf-like intraluminal protrusions in the carotid bulb with emerging implications related to recurrent ischemic stroke.^1,2 Most carotid web cases have been previously described with conventional angiography.^3,4 More recently, the imaging characteristics on CTA have also been established. The typical appearance of a carotid web on CTA is a focal, gracile intraluminal filling defect along the posterior wall of the carotid bulb.^1,5 Superimposed thrombus has also been described, which is thought to be related to sluggish/turbulent blood flow produced by the filling defect.⁵Carotid webs also have been referred to as an atypical variant of fibromuscular dysplasia, with intimal fibrosis and hyperplasia on histology in contrast to the classic, medial variant.^3,6 Typical fibromuscular dysplasia occurs in middle-aged white women, with a classic “string of beads” imaging appearance, and does not have a direct association with ischemic stroke.^6,7Although considered a rare entity, a significant proportion of reported carotid web cases have been associated with recurrent ischemic strokes, most frequently in younger adults who lack other known risk factors.¹ Recent studies have revealed a mean age between 45 and 50 years in patients with carotid webs and associated ipsilateral carotid territory ischemic strokes, occurring more frequently in women than men.^1,5,8 There is limited reporting on the prevalence of carotid webs in the stroke population. A recent report on an Afro-Caribbean population demonstrated a 23% prevalence of carotid webs in young patients with ischemic stroke and a 7% prevalence among control patients.⁸ Up to one-third of all patients presenting with ischemic strokes lack an identifiable cause and are classified as “cryptogenic” in etiology, with most of these cases occurring in younger patients.⁹ Webs may be an under-recognized entity because of their subtle morphology and a lack of familiarity amongst radiologists and clinicians with this lesion. They could account for a significant portion of cryptogenic strokes, particularly in young adults.The purpose of our study was to determine the prevalence of carotid webs in a group of patients previously classified as having cryptogenic stroke.     

Diffusion-Weighted MRI “Claw Sign” Improves Differentiation of Infectious from Degenerative Modic Type 1 Signal Changes of the Spine

BACKGROUND AND PURPOSE:Modic type 1 degenerative signal changes can mimic/suggest infection, leading to additional costly and sometimes invasive investigations. This retrospective study analyzes the utility and accuracy of a novel, diffusion-weighted “claw sign” for distinguishing symptomatic type 1 degeneration from vertebral diskitis/osteomyelitis.MATERIALS AND METHODS:Seventy-three patients with imaging features resembling type 1 degeneration were classified clinically into 3 groups: true degenerative type 1 changes (n = 33), confirmed diskitis/osteomyelitis (n = 20), and radiologically suspected infection later disproved clinically (n = 20). A claw sign was defined on DWI as well-marginated, linear, regions of high signal situated within the adjacent vertebral bodies at the interface of normal with abnormal marrow. Two blinded neuroradiologists independently rated the presence of the claw sign, along with T2 disk signal and disk and endplate enhancement to determine the utility of each for identifying degeneration versus infection.RESULTS:When the 2 neuroradiologists identified a definite claw, 38 of 39 patients (97%) and 29 of 29 patients (100%) proved to be infection-free. When the readers identified a probable claw, 14 of 14 patients (100%) and 16 of 19 patients (84%) proved to be infection-free. Conversely, when the readers identified the absence of claw sign (diffuse DWI pattern), there was proved infection in 17 of 17 cases (100%) and 13 of 14 cases (93%).CONCLUSIONS:In patients with type 1 signal changes of the vertebral disk space, a claw sign is highly suggestive of degeneration and its absence strongly suggests diskitis/osteomyelitis.

Diffusion-weighted imaging is a critical tool for the evaluation of brain diseases, including ischemia, infection, and inflammation. Recently DWI has gained increasing use in diagnosing pathology in the spine, despite cited limitations,^1,2 and is becoming valuable in the assessment of a variety of disease processes, including tumor and infection.^3–13 Modic type 1 degenerative signal changes on conventional MR imaging sequences can mimic or suggest infection, leading to additional costly and sometimes invasive investigations.^14–17 This study assesses the utility of a specific pattern of diffusion abnormality, the “claw sign,” for confirming the presence of true degenerative endplate changes and reducing concern for possible vertebral diskitis/osteomyelitis.     

The “White Gray Sign” Identifies the Central Sulcus on 3T High-Resolution T1-Weighted Images

BACKGROUND AND PURPOSE:The central sulcus is an important anatomic landmark, but most methods of identifying it rely on variable gyral and sulcal patterns. We describe and assess the accuracy of reduced gray-white contrast along the central sulcus, an observation we term the “white gray sign.”MATERIALS AND METHODS:We conducted a retrospective review of 51 fMRIs with a T1-weighted 3D inversion recovery fast-spoiled gradient-echo and concomitant hand-motor fMRI, which served as confirmation for the location of the central sulcus. To measure gray-white contrast across the central and adjacent sulci, we performed a quantitative analysis of 25 normal hemispheres along the anterior and posterior cortices and intervening white matter of the pre- and postcentral gyri. 3D inversion recovery fast-spoiled gradient-echo axial images from 51 fMRIs were then evaluated by 2 raters for the presence of the white gray sign as well as additional established signs of the central sulcus: the bracket, cortical thickness, omega, and T signs.RESULTS:The mean gray-white contrast along the central sulcus was 0.218 anteriorly and 0.237 posteriorly, compared with 0.320 and 0.295 along the posterior precentral and anterior postcentral sulci, respectively (P < .001). Both raters correctly identified the central sulcus in all 35 normal and 16 abnormal hemispheres. The white gray sign had the highest agreement of all signs between raters and was rated as present the most often among all the signs.CONCLUSIONS:Reduced gray-white contrast around the central sulcus is a reliable sign for identification of the central sulcus on 3D inversion recovery fast-spoiled gradient-echo images.

The central sulcus is an important anatomic landmark that defines the location of the primary motor cortex, a region of the brain critical for all essential motor tasks. Because injury to this region has irreversible consequences and other brain regions cannot compensate for its loss,¹ it is important to clearly identify the central sulcus for surgical planning, especially in the context of focal brain lesions. With knowledge of the location of the central sulcus, DTI and tractography can be used to identify the corticospinal tract emanating from the primary motor cortex. fMRI is a proven technique to identify the primary motor cortex for surgical planning.^2–6 It is still desirable, however, to identify the central sulcus from structural imaging for several reasons: this can provide an estimate of the proximity of a lesion to the motor strip to determine the necessity of fMRI, guide the tasks chosen for fMRI, serve as a surrogate if fMRI is not possible because of patient cooperation and compliance or technical factors, and assist in determining the risks of surgery.⁷Numerous methods besides fMRI for identifying the central sulcus have been previously described on both CT and MR imaging. Most rely on identifying gyral and sulcal patterns and relationships,^8–13 which can be variable. Others involve complex image reformatting that most clinicians are untrained to produce or interpret.^14,15 Only a few signs, such as the difference in cortical thickness across the central sulcus, are based on differences in the underlying cytoarchitecture of the sensorimotor cortex.^16,17 Histologic studies and postmortem ex vivo high-resolution imaging have shown that in addition to the variation of the thickness of the 6 cellular layers of the sensorimotor cortex, there are also differences in myelin content that should be appreciable on MR imaging.^18–21 Based on this latter histologic finding, we describe the “white gray sign,” which refers to the inherent increased T1 signal of the anterior and posterior cortices along the central sulcus, giving this gray matter a more white appearance (Fig 1). Specifically, we measure this contrast and assess the accuracy of this sign in identifying the central sulcus with reference to the criterion standard of fMRI.Open in a separate windowFig 1.The “white gray sign.” Axial high-resolution 3D inversion recovery fast-spoiled gradient-echo T1-weighted image demonstrates decreased gray-white contrast of the anterior and posterior cortices along the central sulcus (white arrow).     

Mechanical Thrombectomy of Distal Occlusions in the Anterior Cerebral Artery: Recanalization Rates,Periprocedural Complications,and Clinical Outcome

BACKGROUND AND PURPOSE:Patients with acute ischemic stroke in the anterior circulation are at risk for either primary or, following mechanical thrombectomy, secondary occlusion of the anterior cerebral artery. Because previous studies had only a limited informative value, we report our data concerning the frequency and location of distal anterior cerebral artery occlusions, recanalization rates, periprocedural complications, and clinical outcome.MATERIALS AND METHODS:We performed a retrospective analysis of prospectively collected data of patients with acute ischemic stroke undergoing mechanical thrombectomy in the anterior circulation between June 2010 and April 2015.RESULTS:Of 368 patients included in this analysis, we identified 30 (8.1%) with either primary (n = 17, 4.6%) or secondary (n = 13, 3.5%) embolic occlusion of the distal anterior cerebral artery. The recanalization rate after placement of a stent retriever was 88%. Periprocedural complications were rare and included vasospasms (n = 3, 10%) and dissection (n = 1, 3.3%). However, 16 (53.5%) patients sustained an (at least partial) infarction of the anterior cerebral artery territory. Ninety days after the ictus, clinical outcome according to the modified Rankin Scale score was the following: 0–2, n = 11 (36.6%); 3–4, n = 9 (30%); 5–6, n = 10 (33.3%).CONCLUSIONS:Occlusions of the distal anterior cerebral artery affect approximately 8% of patients with acute ischemic stroke in the anterior circulation receiving mechanical thrombectomy. Despite a high recanalization rate and a low complication rate, subsequent (partial) infarction in the anterior cerebral artery territory occurs in approximately half of patients. Fortunately, clinical outcome appears not to be predominately unfavorable.

Mechanical thrombectomy (MT) is an effective treatment in acute ischemic stroke secondary to a large-vessel occlusion.^1–4 Patients with acute ischemic stroke secondary to an occlusion of the internal carotid artery–T, middle cerebral artery trunk (M1), or MCA secondary division (M2) have relatively high rates of revascularization and favorable clinical outcomes after MT.^5,6 Unfortunately, for patients with ICA-T occlusions and MCA occlusions, there is a risk of approximately 8.6%–11.4% for secondary emboli into the anterior cerebral artery (ACA), especially the distal branches such as the pericallosal artery, during MT.^2,7,8 Although various technical possibilities, such as proximal flow control or combined aspiration, have been recommended to reduce the risk of secondary emboli^9–13, occlusions of the distal ACA occur.Regardless of the cause of the occlusion (primary occlusion or secondary emboli during MT), cerebral infarctions in the ACA territory may cause relevant clinical deficits by affecting the primary or supplementary motor areas.¹⁴ In a previous, relatively small patient cohort (n = 6), treatment of secondary ACA occlusions was technically successful in 80% of the cases and uneventful in all instances.⁷We present data on the frequency and location of distal ACA occlusions, recanalization rates, periprocedural complications, and clinical outcome.     

Middle Cerebral Artery Stenosis in Patients with Acute Ischemic Stroke and TIA in Israel

BACKGROUND AND PURPOSE:Middle cerebral artery stenosis is not frequent but a well-established cause of first and recurrent ischemic stroke. Our aim was to investigate middle cerebral artery stenosis in the biethnic (Jewish and Arab) population of patients with acute ischemic stroke and transient ischemic attack in northern Israel.MATERIALS AND METHODS:The study population included 1344 patients from the stroke data registry who had been hospitalized in the neurologic department because of acute ischemic stroke (1041) or TIA (303) and had undergone transcranial Doppler sonographic examination during the hospitalization.RESULTS:Of the 1344 patients, 120 (8.9%) were found to have MCA stenosis. The patients with intracranial stenosis were older and had more vascular risk factors (hypertension, diabetes, and hyperlipidemia) and vascular diseases (ischemic heart and peripheral vascular disease) than those without intracranial stenosis. Logistic regression analysis revealed that diabetes (P = .002) and peripheral vascular disease (P = .01), but not ethnicity, were independent and significant predictors for the presence of MCA stenosis.CONCLUSIONS:An independent and significant correlation was found between MCA stenosis and vascular risk factors (diabetes mellitus) and vascular diseases, thus emphasizing the similarity of intracranial MCA stenosis and other vascular diseases originating from atherosclerosis. There was no influence of ethnicity on intracranial stenosis in our population.

Intracranial stenosis is most commonly due to an atherosclerotic lesion of the intracranial vessels, leading to subsequent narrowing or occlusion of these vessels.^1,2 This condition is being increasingly recognized as an important and underestimated etiology in acute ischemic stroke.^3–5 Differences in the prevalence of intracranial stenosis in various populations have been reported, with the most vulnerable patients seeming to be Asians, Hispanics, and African Americans.^6–10 Because intracranial stenosis usually represents an atherosclerotic lesion, it is not surprising that there is a clear correlation between intracranial stenosis and vascular diseases and vascular risk factors.^11–15The aim of the present study was to search for possible determinants of potentially symptomatic middle cerebral artery stenosis in patients with stroke and transient ischemic attack in a biethnic (Jewish and Arab) population of northern Israel.Many studies in the literature suggest different transcranial Doppler sonography (TCD) parameters (peak systolic velocity, mean velocity) and different values as cutoffs for the diagnosis of intracranial stenosis. There are also many different definitions in the literature of intracranial stenosis (eg, “mild, moderate, and severe,” “less and more than 50%,” “50%–69% and more than 70%,” and so forth). There are still no generally accepted criteria for moderate intracranial stenosis. In this study, potentially symptomatic intracranial stenosis was defined as cases in which TCD examination showed a peak velocity in the middle cerebral artery, either left or right, of ≥140 cm/s. This value was used by some researchers as a criterion correlating with MCA stenosis of ≥50%.^3,16     

Centripetal Propagation of Vasoconstriction at the Time of Headache Resolution in Patients with Reversible Cerebral Vasoconstriction Syndrome

BACKGROUND AND PURPOSE:Reversible cerebral vasoconstriction syndrome is characterized by thunderclap headache and diffuse segmental vasoconstriction that resolves spontaneously within 3 months. Previous reports have proposed that vasoconstriction first involves small distal arteries and then progresses toward major vessels at the time of thunderclap headache remission. The purpose of this study was to confirm centripetal propagation of vasoconstriction on MRA at the time of thunderclap headache remission compared with MRA at the time of reversible cerebral vasoconstriction syndrome onset.MATERIALS AND METHODS:Of the 39 patients diagnosed with reversible cerebral vasoconstriction syndrome at our hospital during the study period, participants comprised the 16 patients who underwent MR imaging, including MRA, within 72 hours of reversible cerebral vasoconstriction syndrome onset (initial MRA) and within 48 hours of thunderclap headache remission.RESULTS:In 14 of the 16 patients (87.5%), centripetal propagation of vasoconstriction occurred from the initial MRA to remission of thunderclap headache, with typical segmental vasoconstriction of major vessels. These mainly involved the M1 portion of the MCA (10 cases), P1 portion of the posterior cerebral artery (10 cases), and A1 portion of the anterior cerebral artery (5 cases).CONCLUSIONS:This study found evidence of centripetal propagation of vasoconstriction on MRA obtained at the time of thunderclap headache remission, compared with MRA obtained at the time of reversible cerebral vasoconstriction syndrome onset. If clinicians remain unsure of the diagnosis during early-stage reversible cerebral vasoconstriction syndrome, this time point represents the best opportunity to diagnose reversible cerebral vasoconstriction syndrome with confidence.

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by thunderclap headache (TCH) and diffuse segmental constriction of cerebral arteries that resolves spontaneously within 3 months.^1,2 RCVS can be spontaneous or evoked by various factors such as postpartum status, vasoactive drugs, catecholamine-secreting tumors, immunosuppressants, or blood products.^3,4 RCVS is poorly understood and has recently been estimated to be more common than previously thought.² Unpredictable and transient failure of the regulation of cerebral arterial tone through sympathetic overactivity is thought to play a role in the development of RCVS.^1,5TCH is usually the first symptom of RCVS, and typically recurs for 1–2 weeks after onset.^3–5 The final TCH occurs at a mean of 7–8 days after onset, and all noteworthy headaches are generally gone within 3 weeks after onset.^4,6,7 Conventional DSA was crucial to the diagnosis of RCVS in early case reports and typically showed diffuse segmental vasoconstrictions involving major vessels, like a “string of beads” or “string of sausages.”⁴ More recently, MRA has been widely used as a noninferior tool to evaluate vasoconstriction in patients with RCVS.^3,4,6 Findings of typical segmental vasoconstriction of major vessels are not obtained in about one-third of patients with RCVS if the initial MRA is performed within 10 days of headache onset.^4,6,8 Ducros et al^4,9 postulated that the arterial abnormalities first involve small distal arteries and then progress toward major vessels.This study retrospectively investigated whether centripetal propagation of vasoconstriction on MRA at the time of TCH remission was evident compared with MRA at the time of RCVS onset.     

Favorable Bridging Therapy Based on DWI-FLAIR Mismatch in Patients with Unclear-Onset Stroke

BACKGROUND AND PURPOSE:Standard selection criteria for revascularization therapy usually exclude patients with unclear-onset stroke. Our aim was to evaluate the efficacy and safety of revascularization therapy in patients with unclear-onset stroke in the anterior circulation and to identify the predictive factors for favorable clinical outcome.MATERIALS AND METHODS:We retrospectively analyzed 41 consecutive patients presenting with acute stroke with unknown time of onset treated by intravenous thrombolysis and/or mechanical thrombectomy. Only patients without well-developed fluid-attenuated inversion recovery changes of acute diffusion lesions on MR imaging were enrolled. Twenty-one patients were treated by intravenous thrombolysis; 19 received, simultaneously, intravenous thrombolysis and mechanical thrombectomy (as a bridging therapy); and 1 patient, endovascular therapy alone. Clinical outcome was evaluated at 90 days by using the mRS. Mortality and symptomatic intracranial hemorrhage were also reported.RESULTS:Median patient age was 72 years (range, 17–89 years). Mean initial NIHSS score was 14.5 ± 5.7. Successful recanalization (TICI 2b–3) was assessed in 61% of patients presenting with an arterial occlusion, symptomatic intracranial hemorrhage occurred in 2 patients (4.9%), and 3 (7.3%) patients died. After 90 days, favorable outcome (mRS 0–2) was observed in 25 (61%) patients. Following multivariate analysis, initial NIHSS score (OR, 1.43; 95% CI, 1.13–1.82; P = .003) and bridging therapy (OR, 37.92; 95% CI, 2.43–591.35; P = .009) were independently associated with a favorable outcome at 3 months.CONCLUSIONS:The study demonstrates the safety and good clinical outcome of acute recanalization therapy in patients with acute stroke in the anterior circulation and an unknown time of onset and a DWI/FLAIR mismatch on imaging. Moreover, bridging therapy versus intravenous thrombolysis alone was independently associated with favorable outcome at 3 months.

Acute ischemic strokes with an unknown time of symptom onset occur in approximately 25% of patients.¹ Hence, these patients are usually excluded from intravenous thrombolysis (IVT).² However, many patients with an unknown stroke onset could also benefit from this treatment. In a subset of these patients, it has been shown that the clinical features and imaging characteristics do not differ significantly from those in patients with a known time of onset.¹ MR imaging could be helpful if it is used as a “clock” for stroke of unknown time onset; indeed, in a recent multicenter observational study of patients with stroke with known time of symptom onset, the DWI-FLAIR mismatch, defined by positive findings on DWI and negative findings on FLAIR, was effective in identifying patients within 4.5 hours of symptom onset.³To date, limited studies have focused on the safety and effectiveness of IVT in patients with a stroke of unknown onset time, especially by using MR imaging–specific eligibility criteria.^4–9 Only a few reports have evaluated the feasibility of endovascular therapies in patients with wake-up stroke.^10–12 Recently, randomized studies have demonstrated that mechanical thrombectomy is an alternative and synergistic method of treatment to IVT in acute ischemic stroke, with a higher recanalization rate (66%–100%) and a more favorable outcome (32.6%–71%).^13–17The aim of this study was to describe the experience of our center with 41 patients presenting with a stroke of an unknown time of symptom onset in the anterior circulation, who were treated by using a coalescent stroke-management protocol with IVT, mechanical thrombectomy, or bridging therapy based on DWI/FLAIR mismatch. We also assessed predictive factors for favorable outcome at 3 months and evaluated the feasibility, safety, and efficacy of revascularization therapy in these patients.     

FRED Flow Diverter: A Study on Safety and Efficacy in a Consecutive Group of 50 Patients

BACKGROUND AND PURPOSE:Endovascular flow diverters are increasingly used for the treatment of cerebral aneurysms. We assessed the safety and efficacy of the Flow-Redirection Endoluminal Device (FRED) in a consecutive series of 50 patients.MATERIALS AND METHODS:Inclusion criteria were wide-neck, blister-like, or fusiform/dissecting aneurysms independent of size, treated with the FRED between February 2014 and May 2015. Assessment criteria were aneurysm occlusion, manifest ischemic stroke, bleeding, or death. The occlusion rate was assessed at 3 months with flat panel CT and at 6 months with DSA by using the Raymond classification and the O''Kelly-Marotta grading scale.RESULTS:Fifty patients with 52 aneurysms were treated with 54 FREDs; 20 patients were treated with the FRED and coils. Aneurysm size ranged from 2.0 to 18.5 mm. Deployment of the FRED was successful in all cases. There were no device-associated complications. One patient developed mild stroke symptoms that fully receded within days. There have been no late-term complications so far and no treatment-related mortality. Initial follow-up at 3 months showed complete occlusion in 72.3% of the overall study group, Six-month follow-up showed total and remnant-neck occlusion in 87.2% of patients, distributed over 81.5% of the FRED-only cases and 95.0% of the cases with combined treatment.CONCLUSIONS:The FRED flow diverter is a safe device for the treatment of cerebral aneurysms of various types. Our data reveal high occlusion rates at 3 and 6 months, comparable with those in other flow diverters. Long-term occlusion rates are expected.

Endovascular treatment has become the therapy of choice for intracranial aneurysms.^1–3 In addition to the well-established embolization with coils, supported by balloons or stents,^4–6 flow-modulating stents are increasingly used for dedicated aneurysms.⁷Flow diverters can cause intra-aneurysmal thrombosis and thus occlusion.^8–19 This outcome is achieved by a narrowly braided stent wall, which, on the other hand, allows the blood to pass through to perforator arteries or major branches where the pressure gradient is high enough.The Flow-Redirection Endoluminal Device (FRED; MicroVention, Tustin, California) uses a new principle because it combines an outer, self-expanding and dimensionally stable open-pored stent with an inner, narrowly braided stent. It is intended to combine easy deployment with flow-redirecting properties. The ends of the outer layer (“flared ends”) exceed the inner layer on each side by approximately 3 mm where there is little or no flow-diverting effect.^12,20We report our results for safety and efficacy in a consecutive series of 50 patients treated with the FRED flow diverter with incidental cerebral aneurysms or those who were retreated after initial coiling in SAH.     

Endovascular Cooling Catheter for Selective Brain Hypothermia: An Animal Feasibility Study of Cooling Performance

BACKGROUND AND PURPOSE:Therapeutic hypothermia represents a promising neuroprotective treatment in acute ischemic stroke. Selective cerebral hypothermia applied early, prior to and during endovascular mechanical recanalization therapy, may be beneficial in the critical phase of reperfusion. We aimed to assess the feasibility of a new intracarotid cooling catheter in an animal model.MATERIALS AND METHODS:Nine adult sheep were included. Temperature probes were introduced into the frontal and temporal brain cortices bilaterally. The cooling catheter system was introduced into a common carotid artery. Selective blood cooling was applied for 180 minutes. Systemic and local brain temperatures were measured during cooling and rewarming. Common carotid artery diameters and flow were measured angiographically and by Doppler sonography.RESULTS:The common carotid artery diameter was between 6.7 and 7.3 mm. Common carotid artery blood flow velocities increased moderately during cooling and after catheter removal. Maximum cerebral cooling in the ipsilateral temporal cortex was −4.7°C (95% CI, −5.1 to −4.0°C). Ipsilateral brain temperatures dropped significantly faster and became lower compared with the contralateral cortex with maximum temperature difference of −1.3°C (95% CI, −1.5 to −1.0°C; P < .0001) and compared with systemic temperature (−1.4°C; 95% CI, −1.7 to −1.0°C; P < .0001).CONCLUSIONS:Sheep proved a feasible animal model for the intracarotid cooling catheter. Fast induction of selective mild hypothermia was achieved within the cooled cerebral hemisphere, with stable temperature gradients in the contralateral brain and systemic blood. Further studies are required to demonstrate any therapeutic benefit of selective cerebral cooling in a stroke model.

Therapeutic hypothermia (TH) is an established neuroprotective therapy in patients after cardiac arrest¹ and in neonates with severe asphyxia.² Recently, the feasibility and safety of TH in patients with acute ischemic stroke was proved in controlled studies,^3–6 and 2 multicenter, randomized clinical trials (EuroHYP-1 and ICTuS 2/3)^7,8 are currently underway to study its efficacy.Patients with stroke with large-artery occlusions benefit from endovascular recanalization by mechanical thrombectomy (MT).^9–13 However, reperfusion of ischemic brain tissue may induce additional damage and hemorrhagic transformation, potentially limiting the benefits of recanalization. Current systemic cooling approaches involve long induction times, so the time window for TH during the critical reperfusion phase may still be missed for many patients.¹⁴Recently, we have developed an intracarotid cooling catheter system for combined MT and selective TH treatment.¹⁵ It simultaneously serves as an access for the intracranial MT procedure and enables early cooling of the ischemic penumbra via collaterals before recanalization, to then provide a “cold reperfusion” of the ischemic core during and after MT treatment. The latter is expected to be a critical determinant of clinical outcome.⁷ Moreover, selective cooling may reduce systemic adverse events from TH.In this study, we aimed to assess the feasibility of the new cooling catheter in a large animal model with continuous monitoring of systemic and local cortical brain temperatures.     

Three-Territory DWI Acute Infarcts: Diagnostic Value in Cancer-Associated Hypercoagulation Stroke (Trousseau Syndrome)

BACKGROUND AND PURPOSE:DWI infarcts involving the bilateral anterior and posterior circulation suggest an embolic etiology. In the absence of an identifiable embolic source, we analyzed DWI lesions involving these 3 cerebral territories to determine the diagnostic value for ischemic infarction caused by cancer-associated hypercoagulation.MATERIALS AND METHODS:A retrospective analysis of all brain MR imaging studies at our institution from July 2014 to June 2015 was conducted, yielding 4075 studies. Of those, 17% (n = 709) contained the terms “restricted-diffusion” plus either “numerous,” “innumerable,” “multiple,” or “bilateral.” Of these 709 reports, 6% (n = 41) of DWI lesions involving 3 or more vascular territories of the bilateral anterior and posterior circulation were analyzed.RESULTS:Of the 41 patients, 19 separate etiologies were identified, the most frequent being malignancy-related infarctions (22% [n = 9]) and hypoxic-ischemic injury (12% [n = 5]). Only 2 patients had an indeterminate etiology. The most frequent etiology of infarctions not suspected clinically or radiographically was malignancy (P < .001). Infarctions of malignancy had a characteristic appearance, being nonenhancing, nonring-appearing clusters or single areas of restricted diffusion of 0.5–2 cm with a peripheral location or larger vascular territories, uncommonly in a watershed distribution, and with absence of diffuse cortical ribbon or deep gray nuclei involvement.CONCLUSIONS:Approximately 1 in 5 ischemic infarcts in patients with DWI lesions involving 3 vessel territories are malignancy related. In the absence of an identifiable embolic source, ischemic infarction with cancer-associated hypercoagulation accounts for 75% of cases. Cancer-associated hypercoagulation infarction should be considered, particularly when no other cause is apparent.

Up to 15% of patients with malignancy may experience a thromboembolic cerebrovascular event during their clinical course.¹ In addition, malignancy is frequently overlooked as a cause of stroke and is commonly undiagnosed until a second event occurs.² Though the paraneoplastic hypercoagulable state is complex and not fully understood, it is an established mechanism of thrombosis in malignancy. The importance of diagnosing cancer-associated hypercoagulation is appreciated because it may be the heralding manifestation of occult malignancy. Treatment with heparin has been demonstrated effective in preventing thrombotic events, including stroke.^3,4Trousseau syndrome (TS) is a hypercoagulable state, associated with cancer, that includes various disorders probably involving multiple overlapping mechanisms. It has been suggested the term “Trousseau syndrome” be restricted to unexplained thrombotic events that either precede the diagnosis of an occult visceral malignancy or appear concomitantly with the tumor.⁵ Cerebral infarction, mostly caused by in situ thrombosis in medium and small vessels, is thought to be related to the prothrombic state of TS. Verrucous endocarditises associated with cerebral emboli, infection, or therapy-related strokes are alternative causes of ischemic infarction.^2,6 Given the familiar usage of TS by some authors to refer to cancer-associated hypercoagulation,⁵ we use TS in that context in this discussion.DWI primarily defines ischemic infarcts in malignancy as small and involving multiple vessel territories,^6–9 with the number of territories involved correlating with the likelihood of this syndrome.^4,10–12 However, studies specifically evaluating MR imaging in cerebral infarction with TS and its diagnostic value in establishing causality are lacking. Distinct from prior reports where patient selection was based on the presence of stroke with malignancy or vice versa, our patient selection was based on the presence of numerous, innumerable, multiple, or bilateral lesions on MR imaging. At our institution, we have experienced many cases of 3–cerebral territory infarctions associated with malignancy. However, the association of 3-territory DWI infarcts and malignancy has not been studied.We speculate that selecting patients by using MR criteria allows for a more accurate assessment of diagnosing TS-related infarction compared with selection criteria using history of stroke and cancer because the potential for error exists when cancer history is overlooked or undiagnosed. In this study, we assessed the etiology of DWI-defined 3-territory infarcts, with attention to their diagnostic value in TS-related stroke.     

Different Characteristics of the Corticospinal Tract According to the Cerebral Origin: DTI Study

BACKGROUND AND PURPOSE:Little is known about differences in corticospinal tract fibers according to cerebral origin. Using diffusion tensor tractography, we attempted to investigate the characteristics of the CST according to the cerebral origin in the human brain.MATERIALS AND METHODS:Thirty-six healthy subjects were recruited for this study. A 1.5T Gyroscan Intera system was used for acquisition of DTI. CSTs were reconstructed by selection of fibers passing through seed and target ROIs: seed ROIs, the area of the CST at the pontomedullary junction; target ROIs, the primary motor cortex, the primary somatosensory cortex, the dorsal premotor cortex, and the supplementary motor area.RESULTS:A significant difference in tract volume was observed in each ROI (P < .05): M1 (2373.6, 36.9%), S1 (2037.7, 31.7%), SMA (1588.0, 24.7%), and dPMC (429.8, 6.7%). Regarding fractional anisotropy values, the dPMC or SMA showed higher values than the M1 or S1; however, the opposite occurred in terms of the mean diffusivity value (P < .05). In addition, fractional anisotropy and mean diffusivity values of the dPMC differed from those of the SMA (P < .05); in contrast, no significant difference was observed between the M1 and S1 (P > .05).CONCLUSIONS:Tract volume was found to differ according to cerebral origin and was, in descending order, M1, S1, SMA, and dPMC. In addition, the directionality and diffusivity of CST fibers in the SMA and the dPMC differed from those of the M1 and S1, which showed similar characteristics.

The corticospinal tract is a major neural tract for motor function in the human brain.^1–5 The CST is known be involved mainly in movement execution of distal extremities, particularly fine-motor activities of the hand.^1–5 The CST originates from various cortical areas, such as the secondary motor area, the parietal cortex, and the primary motor cortex. The multiple cerebral origins of the CST appear to be important in terms of multiple functions of CST fibers and motor recovery mechanisms: perilesional reorganization following M1 injury.^6–10 Many previous studies have reported differences in characteristics of CST fibers, in terms of the amount of CST fibers and function, according to the origin of the cerebral cortex.^11–18 Most of these studies have used animal brains because only postmortem histologic studies or microelectrode stimulation studies have been used for research on the human brain.^11,14–17By contrast, diffusion tensor tractography, a technique derived from DTI, allows 3D visualization and estimation of the CST.^19–21 Several diffusion tensor tractography studies have reported the characteristics of the whole CST^22–24; however, little is known about differences in CST fibers according to the cerebral origin.¹⁷In the current study, by using diffusion tensor tractography, we attempted to investigate the characteristics of the CST according to the cerebral origin in the human brain.     

Screening CT Angiography for Pediatric Blunt Cerebrovascular Injury with Emphasis on the Cervical “Seatbelt Sign”

BACKGROUND AND PURPOSE:There are no standard screening guidelines to evaluate blunt cerebrovascular injury in children. The purpose of this retrospective study was to understand the clinical and radiologic risk factors associated with pediatric blunt cerebrovascular injury on CTA of the neck with primary attention to the cervical “seatbelt sign.”MATERIALS AND METHODS:Radiology reports from 2002 to 2012 were queried for the examination “CTA neck.” The electronic medical record was reviewed for mechanism of injury, Glasgow Coma Scale score, and physical examination findings. Radiology reports from adjunct radiographic studies were reviewed. CTA neck examinations with reported blunt cerebrovascular injury were reviewed to confirm imaging findings. Patients with penetrating injury or those without a history of trauma were excluded.RESULTS:Four hundred sixty-three patients underwent CTA of the neck; 137 had blunt trauma. Forty-two of 85 patients involved in a motor vehicle collision had a cervical seatbelt sign; none had blunt cerebrovascular injury. Nine vessels (4 vertebral arteries, 4 ICAs, 1 common carotid artery) in 8 patients ultimately were diagnosed with various grades (I–IV) of blunt cerebrovascular injury, representing 5.8% (8/137) of the population screened for blunt neck trauma. The mean Glasgow Coma Scale score was significantly lower (P = .02) in the blunt cerebrovascular injury group versus the non-blunt cerebrovascular injury group. Although not statistically significant, patients with blunt cerebrovascular injury had a higher tendency to have additional traumatic injuries, primarily basilar skull fractures (P = .05) and intracranial hemorrhage (P = .13).CONCLUSIONS:A common indication for neck CTA, the cervical seatbelt sign, was not associated with blunt cerebrovascular injury. With the exception of Glasgow Coma Scale score, no single risk factor was statistically significant in predicting vascular injury in this series.

The incidence of blunt cerebrovascular injury (BCVI) in adult-predominant series is estimated at approximately 1% and as high as 2.7% in patients with polytrauma.^1,2 Despite its fairly low incidence, BCVI has potentially catastrophic neurologic sequelae, including serious morbidity with dense neurologic deficits necessitating costly long-term medical care and even death.³ Most current literature supports fairly liberal screening of adult patients based on these studies, especially with the advent of noninvasive CTA having replaced conventional catheter-based angiography.^4,5 Although screening criteria for adults seem to be well-established,^6,7 there are currently no standard screening guidelines to evaluate BCVI in children. Moreover, the current recommendations of the Eastern Association for the Surgery of Trauma (EAST), the organization that has published screening guidelines based on the most extensive review of the available literature on this topic, including 68 references from the National Library of Medicine/National Institutes of Health MEDLINE data base, state that pediatric patients should be evaluated by using the same criteria as those used in the adult population.⁸ This recommendation is based on limited case series data, however, for which prospective scientific evidence is lacking.⁸Two recent retrospective studies have evaluated the applicability of adult criteria set forth by EAST to the pediatric population.^9,10 While one study supported the notion that risk factors for BCVI in children parallel those of adults, the other, in contradistinction, demonstrated that as many as two-thirds of patients experiencing stroke from BCVI did not meet screening criteria according to those used for adults.^9,10At our institution, adult criteria seem to be generally followed by our trauma team colleagues. One criterion contained within the criteria proposed for the general population by authors such as Biffl et al⁶ is that of seatbelt abrasion or seatbelt injury to the anterior neck, the so-called cervical “seatbelt sign” (Fig 1).⁸ While the EAST recommends that the seatbelt sign not be used as an independent criterion without additional risk factors and physical examination findings to stratify patients for screening,⁸ it remains a physical sign that even in isolation, often prompts clinicians to pursue CTA of the neck at our institution and perhaps at many others.Open in a separate windowFig 1.Cervical seatbelt sign. Dermal bruising at the base of the neck, just cephalad to the clavicle indicating injury by a seatbelt. Courtesy of Matthew Clifton, MD, Children''s Healthcare of Atlanta, Atlanta, Georgia.The purpose of this retrospective study was to further understand the risk factors associated with BCVI in children by examining various clinical and radiologic findings on CTA of the neck and adjunct imaging studies, with a primary regard for the predictive value of the cervical seatbelt sign for BCVI.     

New ischemic brain lesions on diffusion-weighted MRI after carotid artery stenting with filter protection: frequency and relationship with plaque morphology

BACKGROUND AND PURPOSE:CAS carries an inherent risk of distal cerebral embolization, precipitating new brain ischemic lesions and neurologic symptoms. Our purpose was to evaluate the frequency of new ischemic lesions found on DWI after protected CAS placement and to determine its association with plaque morphology.MATERIALS AND METHODS:Fifty patients (mean age 65.13 ± 7.08 years) with moderate and severe internal carotid artery stenosis underwent CAS with distal filter protection. Fibrolipid and fibrocalcified plaque morphology was determined by sonography according to the relative contribution of echogenic and echolucent material, and by multisection CT using plaque attenuation. There were 46.81% of patients with fibrolipid and 53.19% with fibrocalcified plaques. DWI was performed before and 24 hours after CAS.RESULTS:Seven (14.89%) patients showed new lesions. Four (8.51%) had 6 new lesions inside the treated vascular territory. Three had a single lesion and 1 patient had 3 lesions (mean: 1.5 ± 1). Most lesions (66.66%) were subcortical, with a mean diameter of 9 mm (range 5–15 mm). All lesions occurred in the area supplied by the middle cerebral artery and were clinically silent. A significant relationship was found between plaque morphology and the appearance of new lesions. Patients with fibrolipid plaques had a significantly higher number of new lesions compared with patients with fibrocalcified plaques (P = .041). The absolute risk of new lesions in the fibrolipid group was 18.18%.CONCLUSIONS:New ischemic lesions were observed in the treated vascular territory in 8.51% of patients. The appearance of new ischemic lesions was significantly related to the plaque morphology. Fibrolipid plaques were associated with higher numbers of new lesions.

CAS carries an inherent risk of distal cerebral embolization, precipitating new brain ischemic lesions and neurologic symptoms.^1–4 This has led to the development and widespread application of cerebral protection devices.^5,6 The most widely used devices are those based on distal filter placement that capture emboli dislodged from plaque; however, their application may result in additional complications.^7–12Several reviews have reported contradictory data concerning the rate of stroke and ischemia after protected versus unprotected stent placement.^3,13–15 The frequency of new ischemic lesions after CAS may be associated with numerous factors, such as clinical status, vascular anatomy, plaque morphology, and complexity. Therefore, the need to identify patients at risk for embolic events has become increasingly important. The morphologic characteristics of atherosclerotic carotid plaques may be useful in heralding embolic potential in the carotid arteries. Several authors have reported that plaques in the carotid arteries that are associated with large lipid pools or soft extracellular lipid are more prone to rupture and production of emboli.¹⁶ DWI is the most sensitive tool for the detection of neurologically silent or asymptomatic infarcts at a very early stage.^17–19The aim of this study was to determine the frequency of new ischemic DWI lesions in patients with moderate and severe ICA stenosis after protected CAS using a filter device, and to determine its potential association with plaque morphology.     

Complications of Endovascular Treatment for Acute Stroke in the SWIFT Trial with Solitaire and Merci Devices

BACKGROUND AND PURPOSE:Treatment of patients with ischemic stroke after endovascular treatment requires in-depth knowledge of complications. The goal of this study was to make endovascular treatment for acute ischemic stroke safer through an in-depth review of the major periprocedural complications observed in the Solitaire FR With Intention for Thrombectomy (SWIFT) trial.MATERIALS AND METHODS:The SWIFT data base was searched for major peri-procedural complications defined as symptomatic intracranial hemorrhage within 36 hours, SAH, air emboli, vessel dissection, major groin complications, and emboli to new vascular territories.RESULTS:Major peri-procedural complications occurred in 18 of 144 patients (12.5%) as follows: symptomatic intracranial hemorrhage, 4.9%; air emboli, 1.4%; vessel dissection, 4.2%; major groin complications, 2.8%; and emboli to new vascular territories, 0.7%. Rates of symptomatic intracranial bleeding by subtype were PH1, 0.7%; PH2, 0.7% (PH1 indicates hematoma within ischemic field with some mild space-occupying effect but involving ≤30% of the infarcted area; PH2, hematoma within ischemic field with space-occupying effect involving >30% of the infarcted area); intracranial hemorrhage remote from ischemic zone, 0%; intraventricular hemorrhage, 0.7%; and SAH, 3.5%. We did not observe any statistically significant associations of peri-procedural complications with age; type of treatment center; duration of stroke symptoms; NIHSS score, IV thrombolytics, atrial fibrillation, site of vessel occlusion; rescue therapy administered after endovascular treatment; or device. Comparing the Merci with the Solitaire FR retrieval device, we observed symptomatic cerebral hemorrhage (10.9% versus 1.1%; P = .013); symptomatic SAH (7.3% versus 1.1%; P = .07), air emboli (1.8% versus 1.1%; P = 1.0), emboli to new vascular territories (1.8% versus 0%; P = .38), vessel dissection (1.8% versus 4.5%; P = .65), and major groin complications (3.6% versus 7.9%; P = .48). Angiographic vasospasm was common but without clinical sequelae.CONCLUSIONS:Understanding of procedural complications is important for treatment of patients with stroke after endovascular treatment. We observed fewer endovascular complications with the Solitaire FR device treatment compared with Merci device treatment, particularly symptomatic cerebral hemorrhage.

Intravenous tissue plasminogen activator has been proven to be efficacious in recanalization of occluded intracranial vessels and improvement of clinical outcome for acute ischemic stroke.¹ A meta-analysis of 53 studies including 2066 patients with acute stroke demonstrated a 46.2% overall recanalization rate with IV fibrinolysis.^1,2 However, IV tPA has limited ability to open occlusions of medium and large arteries such as the internal carotid artery, proximal middle cerebral artery, or basilar artery, with recanalization rates reported as low as 10%.^2,3 Because of these limitations, catheter-based approaches for acute ischemic stroke have been developed to directly infuse thrombolytics at the site of the thrombus or mechanically extract and disrupt the clot.^3–13 As with systemic thrombolytics, endovascular treatments for acute ischemic stroke carry the risk of intracranial bleeding. These treatments also carry additional risks related to vascular access, catheter placement, direct vessel injury, and the type of device deployed.The Solitaire FR With Intention for Thrombectomy (SWIFT) trial provides additional information about endovascular approaches for acute stroke and directly compares the Solitaire FR device (Covidien, Irvine, California) with the Merci retrieval device (Stryker Neurovascular, Fremont, California) in a prospective, randomized trial. Results of the primary end point for this study have been reported separately.¹³ Acute stroke trials have consistently highlighted the importance of achieving early reperfusion while keeping procedural complication risks as low as possible. The therapeutic time windows are tight, and gains achieved by flow restoration are easily erased by symptomatic intracranial bleeding caused by procedural complications. The SWIFT trial reports a significant technical advance for mechanical thrombectomy by use of the Solitaire device compared with current technology (Merci retriever); the focus of this report is an in-depth analysis of the major procedural complications of this trial.     

Benign Miliary Osteoma Cutis of the Face: A Common Incidental CT Finding

BACKGROUND AND PURPOSE:Osteoma cutis of the face represents a primary or secondary formation of ossific foci in the facial skin. Its primary form has been sparsely described in the plastic surgery and dermatology literature. As radiologists, we routinely encounter incidental, very small facial calcified nodules on CT studies performed for a variety of unrelated reasons. We hypothesized that this routinely encountered facial calcification represents primary miliary osteoma cutis and is a common, benign, age-related finding.MATERIALS AND METHODS:We retrospectively reviewed 1315 consecutive sinus CTs obtained during an 8-month period and their associated demographics. The number of dermal radiopaque lesions with Hounsfield units of >150 was counted, and we analyzed the association between the prevalence of these lesions and patients'' demographics with logistic regression methods.RESULTS:Five hundred ninety-nine males and 716 females from 4 to 90 years of age were included in the study (mean, 52 versus 51 years; P = .259). Among these, 252 males and 301 females had small facial calcified nodules (42.1% versus 42.0%, P = .971). The patient''s age was a statistically significant predictor for having facial calcified nodules (odds ratio = 1.02, P < .001), while the patient''s sex was not (P = .826).CONCLUSIONS:Facial calcified nodules, observed in routine head and face CT imaging, are common, benign, age-related findings, which have been largely overlooked in the radiology literature. It is a manifestation of primary miliary osteoma cutis.

Osteoma cutis (cutaneous ossification) represents primary or secondary formation of ossific foci in the skin. It was first described by Martin Wilckens in 1858.¹ It is distinguished radiographically and pathologically from calcinosis cutis by the deposition of organized bone matrix, while the latter is characterized by the deposition of amorphous calcium salts within the skin.^2–4 Some consider calcinosis cutis a precursor or the early manifestation of osteoma cutis.⁵ Similar to secondary cutaneous calcification, the etiologies of secondary osteoma cutis have been well-described in the radiology and dermatopathology literature and are attributed to iatrogenic, traumatic, metabolic (eg, Albright hereditary osteodystrophy), inflammatory (eg, acne or dermatomyositis), and neoplastic (eg, basal cell carcinoma) processes.^2,5–7 However, primary or idiopathic osteoma cutis has been sparsely described as a rare disease entity in the plastic surgery and dermatology literature, mostly in the form of case reports.^4,6,8–11The most frequently reported subclass of primary osteoma cutis occurs in the face and scalp soft tissues. It is reported as “miliary osteoma cutis of the face.”^4,10,12,13 Current literature agrees on its idiopathic etiology and its benign, noninvasive, and asymptomatic nature.^4,6,10,12,13 However, there have been varying reports regarding its epidemiology. While several authors describe it as a very rare disease^6,9,12 with slightly increased incidence in elderly or middle-aged women,^2,14,15 other authors report it as a very common entity in the general population,¹⁶ without sex or age predilection.⁶As radiologists, we routinely encounter incidental, punctate facial hypodermal calcifications on CT studies performed for a variety of reasons in patients without clinically recognized underlying dermatopathology (Fig 1). Due to their benign and asymptomatic nature, these incidental facial calcified nodules have been largely overlooked in the imaging literature. We performed a retrospective review of a large CT dataset. Our imaging technique extended the results of a previously reported large, radiographic, cadaveric case series,¹⁶ in an effort to establish that routinely encountered facial dermal calcification/ossification is primary miliary osteoma cutis, a common, benign, age-related finding.Open in a separate windowFig 1.Axial (A), sagittal (B), and coronal (C) CT images of 3 different representative patients demonstrate multiple millimetric scattered facial and scalp hypodermal calcified nodules with varying degrees of severity. A 3D bone window reconstruction of a patient''s sinus CT (D) also demonstrates a relatively large, 4- to 5-mm facial calcified nodule within the right premaxillary skin.     

Pretreatment Advanced Imaging in Patients with Stroke Treated with IV Thrombolysis: Evaluation of a Multihospital Data Base

BACKGROUND AND PURPOSE:CT angiography, CT perfusion, and MR imaging have all been advocated as potentially useful in treatment planning for patients with acute ischemic stroke. We evaluated a large multihospital data base to determine how the use of advanced imaging is evolving in patients treated with intravenous thrombolysis.MATERIALS AND METHODS:Patients with acute ischemic stroke receiving IV thrombolytic therapy from 2008 to 2011 were identified by using the Premier Perspective data base. Mortality and discharge to long-term care rates were compared following multivariate logistic regression between patients who received head CT only versus those who received CTA without CT perfusion, CT perfusion, or MR imaging.RESULTS:Of 12,429 included patients, 7305 (59%) were in the CT group, 2359 (19%) were in the CTA group, 848 (7%) were in the CTP group, and 1917 (15%) were in the MR group. From 2008 to 2011, the percentage of patients receiving head CT only decreased from 64% to 55%, while the percentage who received cerebral CT perfusion increased from 3% to 8%. The use of CT angiography and MR imaging marginally increased (1%–2%). Outcomes were similar between CT only and advanced imaging patients, except discharge to long-term care was slightly more frequent in the CTP group (OR = 1.17 [95% CI, 0.96–1.43]; P = .0412) and MR group (OR = 1.14 [95% CI, 1.01–1.28]; P = .0177) and mortality was lower in the MR group (OR = 0.64 [95% CI, 0.52–0.79]; P < .0001).CONCLUSIONS:Use of advanced imaging is increasing in patients treated with IV thrombolysis. While there were differences in outcomes among imaging groups, the clinical effect of advanced imaging remains unclear.

The potential benefit of intravenous thrombolytic therapy for acute ischemic stroke decreases rapidly with time. Because of wide variability in collateral circulation, time elapsed since onset is a crude indicator of the potential benefit of treatment in each patient. Advanced imaging might provide a means to refine selection of patients who could potentially benefit from revascularization therapy. The advanced imaging techniques that might add clinically useful information in the setting of acute ischemic stroke include CT angiography, CT perfusion, and MR imaging. CT angiography can be used to identify patients with large-artery occlusions potentially amenable to intra-arterial therapy,^1–3 and CT angiography source images have been proposed as a means of evaluating collateral circulation.^4–6 CT perfusion may potentially allow discrimination between salvageable brain (“penumbra”) and brain already doomed to infarction (“ischemic core”)^2,7–10 and thus may be useful in helping to refine selection of patients for IV thrombolysis^11,12 or intra-arterial thrombectomy.^13–15 MR perfusion and diffusion imaging have also been reported to be useful in screening patients for intravenous therapy.^16–22While advanced imaging techniques hold promise for the evaluation of patients with acute ischemic stroke, there is variation in techniques and definitions of parameters that limit wide application and acceptance of these techniques.^4,23–25 There is currently no consensus on a standard imaging approach for acute ischemic stroke. We studied a large data base of hospitals in the United States to assess the recent use of advanced imaging in patients with acute ischemic stroke treated with intravenous thrombolysis, including an evaluation of the use of advanced imaging, with respect to patient outcome.     

CTA Collateral Status and Response to Recanalization in Patients with Acute Ischemic Stroke

BACKGROUND AND PURPOSE:Collateral status at baseline is an independent determinant of clinical outcome among patients with acute ischemic stroke. We sought to identify whether the association between recanalization after intra-arterial acute stroke therapy and favorable clinical response is modified by the presence of good collateral flow assessed on baseline CTA.MATERIALS AND METHODS:Data are from the Keimyung Stroke Registry, a prospective cohort study of patients with acute ischemic stroke from Daegu, South Korea. Patients with M1 segment MCA with or without intracranial ICA occlusions on baseline CTA from May 2004 to July 2009 who also had baseline MR imaging were included. Two readers blinded to all clinical information assessed baseline and follow-up imaging. Leptomeningeal collaterals on baseline CTA were assessed by consensus by use of the regional leptomeningeal score.RESULTS:Among 84 patients (mean age, 65.2 ± 13.2 years; median NIHSS score, 14; interquartile range, 8.5), median time from stroke onset to initial MR imaging was 164 minutes. TICI 2b–3 recanalization was achieved in 38.1% of patients and mRS 0–2 at 90 days in 35.8% of patients. In a multivariable model, the interaction between collateral status and recanalization was significant. Only patients with intermediate or good collaterals who recanalized showed a statistically significant association with good clinical outcome (rate ratio = 3.8; 95% CI, 1.2–12.1). Patients with good and intermediate collaterals who did not achieve recanalization and patients with poor collaterals, even if they achieved recanalization, did not do well.CONCLUSIONS:Patients with good or intermediate collaterals on CTA benefit from intra-arterial therapy, whereas patients with poor collaterals do not benefit from treatment.

Leptomeningeal collaterals are pre-existing anastomoses that connect a small number of distal-most arterioles within the crowns of the cerebral artery trees.^1,2 During an acute stroke, ischemic brain depends on blood flow from these collaterals to survive until the occluded artery is opened.^3–8 This collateral circulation is highly variable and potentially influences the rate at which an infarct grows.^4,8–10 Collateral status at baseline is an independent determinant of clinical outcome among patients with acute ischemic stroke.^3,5,7,8,11 Nonetheless, “effect modification” by collateral status measured noninvasively by use of CTA of the relationship between recanalization and clinical outcome has not been demonstrated before. This tool can be used to select patients for intra-arterial therapy (IAT) through demonstration of a differential clinical response to recanalization by collateral status.In this study, we first demonstrate the concept of validity of collateral status measured by use of CTA among patients presenting with acute ischemic stroke by correlating it with infarct volume on baseline MR DWI and infarct growth over 24 hours. We then demonstrate “effect modification” by collateral status of the relationship between recanalization and clinical outcome in patients with acute ischemic stroke undergoing IAT, thus justifying the use of baseline collateral status on CTA as a patient selection tool for IAT.     

CT Angiographic Features of Symptom-Producing Plaque in Moderate-Grade Carotid Artery Stenosis

BACKGROUND AND PURPOSE:Emerging evidence indicates that plaque imaging can improve stroke risk stratification in patients with carotid artery atherosclerosis. We studied the association between soft and hard (calcified) plaque thickness measurements on CTA and symptomatic disease status (ipsilateral stroke or TIA) in patients with moderate-grade carotid artery stenosis.MATERIALS AND METHODS:We measured soft-plaque and hard-plaque thickness on CTA axial source images in each carotid artery plaque in subjects with NASCET 50%–69% ICA stenosis. We used logistic regression and receiver operating characteristic analyses to assess the strength of the association between thickness measurements and prior stroke or TIA.RESULTS:Twenty of 72 vessels studied (27.7%) had ischemic symptoms ipsilateral to the side of moderate-grade carotid stenosis. Each 1-mm increase in soft plaque resulted in a 3.7 times greater odds of a prior ipsilateral ischemic event (95% CI, 1.9–7.2). Conversely, for each 1-mm increase in hard plaque, the odds of being symptomatic decreased by approximately 80% (OR, 0.22; 95% CI, 0.10%–0.48%). Receiver operating characteristic analysis showed an area under the curve of 0.88 by using soft-plaque thickness measurements to discriminate between asymptomatic and symptomatic plaques. Sensitivity and specificity were optimized by using a maximum soft-plaque thickness of 2.2 mm, which provided a sensitivity of 85% and a specificity of 83%.CONCLUSIONS:Simple CTA plaque-thickness measurements might differentiate symptomatic and asymptomatic moderate-grade carotid artery plaque. With further prospective validation, CTA plaque measures could function as an easily implementable tool for risk stratification in carotid artery disease.

Moderate-grade carotid artery stenosis is a risk factor for stroke, with pooled analysis from randomized controlled trials, including the European Carotid Surgery Trial, NASCET, and Veterans Affairs Symptomatic Trial, suggesting that unoperated patients with moderate-grade stenosis face up to a 20% 5-year risk of stroke.¹ Data pooled from these randomized controlled trials have also shown a modest stroke-risk-reduction benefit from carotid endarterectomy in patients with 50%–69% extracranial ICA stenosis.¹ However, the validity of these data has been questioned in the years since these trials were performed secondary to recent improvements in medical therapy, which have substantially reduced annual stroke rates in patients with carotid disease.^2,3 Consequently, there has been significant recent effort to develop new imaging markers that can identify patients with carotid artery disease at highest risk for stroke beyond luminal-diameter stenosis measurements.The 2 main pathophysiologic mechanisms underlying stroke risk in carotid artery disease are the propensity of plaque to locally embolize^4,5 and downstream hemodynamic compromise (low flow).^4,6,7 Although hypoperfusion and resultant slow flow from carotid disease likely play a role in a subset of strokes occurring in carotid stenosis, plaque instability causing distal embolus may be a relatively more influential etiologic factor for stroke in carotid disease in general.⁸ Although multisequence MR imaging characterization of plaque has allowed the in vivo discrimination of high-risk plaque tissue elements,^9–11 its use in clinical practice has been limited, given the time, expense, and challenge of performing multisequence carotid plaque MR imaging by using a dedicated carotid coil. CTA-based measurements of soft and hard (calcified) plaque determined on axial CTA source images have recently been proposed as potential simple alternative markers of vulnerable plaque in high-grade ICA stenosis.^12,13 Because plaque volumes are relatively smaller in moderate-grade stenosis, it is unclear to what extent such techniques are capable of identifying symptom-producing plaque in this group of patients in whom optimal treatment guidelines are controversial. Therefore, we used a cross-sectional study design to assess the association between plaque thickness measurements obtained from neck CTA and previous stroke or TIA in patients with moderate-grade ICA stenosis.     

Strategies of Collateral Blood Flow Assessment in Ischemic Stroke: Prediction of the Follow-Up Infarct Volume in Conventional and Dynamic CTA

BACKGROUND AND PURPOSE:Collateral blood flow is an important prognostic marker in the acute stroke situation but approaches for assessment vary widely. Our aim was to compare strategies of collateral blood flow assessment in dynamic and conventional CTA in their ability to predict the follow-up infarction volume.MATERIALS AND METHODS:We retrospectively included all patients with an M1 occlusion from an existing cohort of 1912 consecutive patients who underwent initial multimodal stroke CT and follow-up MR imaging or nonenhanced CT. Collateralization was assessed in both conventional CT angiography and dynamic CT angiography by using 3 different collateral grading scores and segmentation of the volume of hypoattenuation. Arterial, arteriovenous, and venous phases were reconstructed for dynamic CT angiography, and all collateral scores and the volume of hypoattenuation were individually assessed for all phases. Different grading systems were compared by using the Bayesian information criterion calculated for multivariate regression analyses (Bayesian information criterion difference = 2–6, “positive”; Bayesian information criterion difference = 6–10, “strong”; Bayesian information criterion difference = >10, “very strong”).RESULTS:One hundred thirty-six patients (mean age, 70.4 years; male sex, 41.2%) were included. In the multivariate analysis, models containing the volume of hypoattenuation showed a significantly better model fit than models containing any of the 3 collateral grading scores in conventional CT angiography (Bayesian information criterion difference = >10) and dynamic CT angiography (Bayesian information criterion difference = >10). All grading systems showed the best model fit in the arteriovenous phase. For the volume of hypoattenuation, model fit was significantly higher for models containing the volume of hypoattenuation as assessed in the arteriovenous phase of dynamic CT angiography compared with the venous phase (Bayesian information criterion difference = 6.2) and the arterial phase of dynamic CT angiography (Bayesian information criterion difference = >10) and in comparison with conventional CT angiography (Bayesian information criterion difference = >10).CONCLUSIONS:The use of dynamic CT angiography within the arteriovenous phase by using quantification of the volume of hypoattenuation is the superior technique for assessment of collateralization among the tested approaches.

In acute ischemic stroke, leptomeningeal collateral vessels provide blood flow to the ischemic bed of the occluded artery.^1,2 The extent of collateralization is an independent predictor of a small-lesion volume on follow-up imaging³ and a favorable clinical outcome.⁴ It has been further shown to predict response to intravenous thrombolysis⁵ and to determine penumbral tissue loss.⁶ Noninvasive imaging of collaterals can be performed by using CT angiography^7,8 or MR angiography.⁹ CTA offers the advantages of a wide availability and short scanning times.One strategy to assess collateral blood flow in CTA is through grading of collateral vessels in the territory of the occluded artery.^4,7,8 Currently, several different grading scores have been published,¹⁰ which differ not only in the number of categories of each score but also in the type of assessment (ie, an assessment relative to the contralateral hemisphere or absolute quantification). The 3 most commonly used scores in the literature include the following: 1) an absolute score assessing the percentage of the ischemic bed in which collateral filling is seen,³ 2) a relative score comparing collateral vessel enhancement within the ischemic bed with similar contralateral vessels,⁸ and 3) a detailed relative score comparing collateral vessel enhancement with similar contralateral vessels within each ASPECTS region.¹¹Another strategy to assess collateral blood flow is through quantification of hypoattenuated brain tissue in CTA source images.^12–15 Whereas hypoattenuation in nonenhanced CT (NECT) images represents the brain tissue net water uptake,¹⁶ hypoattenuation in CT angiography suggests an area receiving limited blood flow, which has been shown to correlate with initial diffusion-weighted images¹⁵ and follow-up lesion size.¹⁴ However, this correlation might be heavily influenced by the time point of image acquisition.¹³Recently, Smit et al¹⁷ demonstrated that conventional CTA can fail to capture delayed collateral enhancement. Delay-insensitive CT angiography with acquisition of multiple timeframes can help overcome this limitation. Its value in assessing the maximal extent of collateralization has been shown in several studies.^5,17,18 However, the time point of image analysis might play an important role in correctly assessing the prognostic value of the collateralization.The aim of our study was the following: 1) to determine the optimal time-phase for reconstruction of the dynamic CTA images to best predict follow-up lesion volume, and 2) to compare the predictive value of the volume of hypoattenuation with different collateral vessel grading scores.     

Inter- and Intraobserver Agreement in Scoring Angiographic Results of Intra-Arterial Stroke Therapy

BACKGROUND AND PURPOSE:Angiographic results are commonly used as surrogate markers of the success of intra-arterial therapies for acute stroke. Inter- and intraobserver agreement in judging angiographic results remain poorly characterized. Our goal was to assess 2 commonly used revascularization scales.MATERIALS AND METHODS:A portfolio of 148 pre- and post treatment images of 37 cases of proximal anterior circulation occlusions was electronically sent to 12 expert observers who were asked to grade treatment outcomes according to recanalization (of arterial occlusive lesion) or reperfusion (TICI) scales. Three expert observers had to score treatment outcomes by using a similar portfolio of 32 patients or when they had full access to all angiographic data, twice for each method 3–12 months apart. Results were analyzed by using κ statistics.RESULTS:Agreement among 9 responding observers was moderate for both the TICI (κ = 0.45 ± 0.01) and arterial occlusive lesion (κ = 0.39 ± 0.16) scales. Agreement was similar (moderate) when 3 observers had access to a portfolio (κ = 0.59 ± 0.06 and 0.49 ± 0.07, respectively) or to the full angiographic data (κ = 0.54 ± 0.06 and 0.59 ± 0.07, respectively). Intraobserver agreement was “fair to moderate” for both methods. Interobserver agreement became “substantial” (>0.6) when outcomes were dichotomized into “success” (TICI 2b, 3; arterial occlusive lesion II, III or “failure”; the results were judged more favorably when the arterial occlusive lesion rather than the TICI scale was used.CONCLUSIONS:There is an important variability in the assessment of angiographic outcomes of endovascular treatments, invalidating comparisons among publications. A simple dichotomous judgment can be used as a surrogate outcome when treatments are assessed by the same observers in randomized trials.

Current therapies of acute stroke aim at rapid restoration of blood flow or revascularization of the occluded territory to salvage ischemic brain tissue. A gamut of methods and devices has been introduced to accomplish revascularization.^1–4 While all may agree that the well-being of the patient at the end of treatment is the most important outcome,⁵ we also need surrogate markers of mechanistic efficacy, directly linked to the effect we are aiming for, to more expediently determine which method or device should be selected to be tested in a more rigorous fashion, because the heterogeneity of presentations ensures that large trials will be needed to show differences in clinical outcomes. In addition, regulatory agencies approve devices according to their ability to restore blood flow.⁶ Thus angiographic scoring systems and a new vocabulary (such as Thrombolysis in Myocardial Infarction [TIMI], TICI, arterial occlusive lesion [AOL], described below) are now used to adjudicate and compare angiographic results of acute stroke therapies.^7–12The precision of outcome scales must be assessed before their widespread use. Testing can be accomplished by asking various individuals to repeatedly but independently categorize the angiographic results of the same patients and by studying intra- and interobserver agreement of the resulting verdicts. Despite notes of concern^13,14 and except for small studies limited to 2–3 observers introducing unusual scales^15,16 or comparing 2 scoring systems obtained from consensus reading,¹⁷ the inter- and intraobserver agreement among multiple observers for commonly used systems has not been rigorously assessed. The aim of the present work was to assess the precision and reproducibility of 2 angiographic outcome scales of intra-arterial therapies, one for recanalization and one for reperfusion: The primary arterial occlusive lesion recanalization scoring method, initially proposed for the Interventional Management of Stroke (IMS) I analyses,¹⁷ and the Thrombolysis in Cerebral Infarction perfusion categories, proposed by the Technology Assessment Committees of the American Society of Interventional and Therapeutic Neuroradiology and the Society of Interventional Radiology.⁷ These scales (with or without some modifications) are being used in recent trials on intra-arterial stroke therapy, such as IMS II and III,¹⁸ the Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR Rescue) trial,¹⁹ and the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Time (ESCAPE) trial (M. Hill, personal communication; May 2013) and others.²⁰