An In Vivo,MRI-Integrated Real-Time Model of Active Contrast Extravasation in Acute Intracerebral Hemorrhage

BACKGROUND AND PURPOSE:The “spot sign” or contrast extravasation is strongly associated with hematoma formation and growth. An animal model of contrast extravasation is important to test existing and novel therapeutic interventions to inform present and future clinical studies. The purpose of this study was to create an animal model of contrast extravasation in acute intracerebral hemorrhage.MATERIALS AND METHODS:Twenty-eight hemispheres of Yorkshire male swine were insonated with an MR imaging–guided focused sonography system following lipid microsphere infusion and mean arterial pressure elevation. The rate of contrast leakage was quantified by using dynamic contrast-enhanced MR imaging and was classified as contrast extravasation or postcontrast leakage by using postcontrast T1. Hematoma volume was measured on gradient recalled-echo MR imaging performed 2 hours postprocedure. Following this procedure, sacrificed brain was subjected to histopathologic examination. Power level, burst length, and blood pressure elevation were correlated with leakage rate, hematoma size, and vessel abnormality extent.RESULTS:Median (intracerebral hemorrhage) contrast extravasation leakage was higher than postcontrast leakage (11.3; 6.3–23.2 versus 2.4; 1.1–3.1 mL/min/100 g; P < .001). Increasing burst length, gradient recalled-echo hematoma (ρ = 0.54; 95% CI, 0.2–0.8; P = .007), and permeability were correlated (ρ = 0.55; 95% CI, 0.1–0.8; P = .02). Median permeability (P = .02), gradient recalled-echo hematoma (P = .02), and dynamic contrast-enhanced volumes (P = .02) were greater at 1000 ms than at 10 ms. Within each burst-length subgroup, incremental contrast leakage was seen with mean arterial pressure elevation (ρ = 0.2–0.8).CONCLUSIONS:We describe a novel MR imaging–integrated real-time swine intracerebral hemorrhage model of acute hematoma growth and contrast extravasation.

Intracerebral hemorrhage (ICH) accounts for 10%–30% of strokes and is the most deadly and disabling stroke type with little improvement in mortality seen during the past 20 years.¹ These characteristics underscore the importance of developing a better understanding of the pathophysiology of ICH formation and growth to facilitate the development of improved therapeutic agents or interventions.² The causative lesion in primary ICH is yet to be elucidated, though pathologic studies demonstrate focal vessel integrity loss in association with blood extravasation into the brain parenchyma.³ Following initial ICH formation, continuous^4,5 or delayed⁶ extravasation results in hematoma expansion,⁷ which is associated with early neurologic deterioration and significant mortality.⁸Several recent studies have shown an association between contrast extravasation (CE) detected on CTA, coined the CTA “spot sign,” and hematoma growth.^9–14 Prospective studies have demonstrated that contrast extravasation independently predicts a larger hematoma size and a poorer clinical outcome.^13,14 These are the first clinical studies to suggest a robust “real-time” imaging marker of hematoma expansion. Three clinical studies are presently enrolling patients dichotomized by the CTA spot sign to validate the prior study findings and to determine the therapeutic efficacy of recombinant factor VIIa or tranexamic acid.^15–17 A more recent study using dynamic spot sign imaging with a biphasic CT perfusion protocol¹⁸ has confirmed 2 patterns of contrast extravasation associated with significantly different rates of leakage. These patterns, comprising a brisker active extravasation (spot sign) and slower postcontrast leakage (PCL),¹⁹ are also demonstrated with early and late structural imaging,^10,19 dynamic CTA/CTP,¹⁸ and biphasic or repeat delayed CTA acquisitions.¹²Morphologic patterns and more recent studies illustrate that the spot sign is not an all-or-none phenomenon but constitutes a spectrum of extravasation.^18,19 The extravasation rate likely significantly impacts timely and clinically meaningful hemostasis.²⁰ A bleeding threshold likely exists beyond which prothrombotic treatment is futile, exposing patients to harmful adverse effects without hope of therapeutic benefit.²¹ Increasingly, new innovative surgical techniques are being developed to address contrast extravasation.²² Knowledge of the impact of the extravasation rate on therapeutic response is critical to stratify patients to the most appropriate therapies. An animal model of acute contrast extravasation in ICH could potentially inform the patient-selection process. We describe a novel MR imaging–integrated real-time swine model of acute hematoma growth and contrast extravasation.     

Transcranial Duplex Sonography Predicts Outcome following an Intracerebral Hemorrhage

BACKGROUND AND PURPOSE:Several radiologic features such as hematoma volume are related to poor outcome following an intracerebral hemorrhage and can be measured with transcranial duplex sonography. We sought to determine the prognostic value of transcranial duplex sonography in patients with intracerebral hemorrhage.MATERIALS AND METHODS:We conducted a prospective study of patients diagnosed with spontaneous intracerebral hemorrhage. Transcranial duplex sonography examinations were performed within 2 hours of baseline CT, and we recorded the following variables: hematoma volume, midline shift, third ventricle and lateral ventricle diameters, and the pulsatility index in both MCAs. We correlated these data with the CT scans and assessed the prognostic value of the transcranial duplex sonography measurements. We assessed early neurologic deterioration during hospitalization and mortality at 1-month follow-up.RESULTS:We included 35 patients with a mean age of 72.2 ± 12.8 years. Median baseline hematoma volume was 9.85 mL (interquartile range, 2.74–68.29 mL). We found good agreement and excellent correlation between transcranial duplex sonography and CT when measuring hematoma volume (r = 0.791; P < .001) and midline shift (r = 0.827; P < .001). The logistic regression analysis with transcranial duplex sonography measurements showed that hematoma volume was an independent predictor of early neurologic deterioration (OR, 1.078; 95% CI, 1.023–1.135) and mortality (OR, 1.089; 95% CI, 1.020–1.160). A second regression analysis with CT variables also demonstrated that hematoma volume was associated with early neurologic deterioration and mortality. When we compared the rating operation curves of both models, their predictive power was similar.CONCLUSIONS:Transcranial duplex sonography showed an excellent correlation with CT in assessing hematoma volume and midline shift in patients with intracerebral hemorrhage. Hematoma volume measured with transcranial duplex sonography was an independent predictor of poor outcome.

Spontaneous intracerebral hemorrhage (ICH) is a major cause of morbidity and mortality,¹ with half of the events related to case fatality occurring within the first 48 hours.² Thus, identifying variables that contribute to early neurologic deterioration (END) and mortality is of enormous importance. An early estimation of the prognosis is crucial for deciding on a treatment plan. Several neuroimaging prognostic factors include hematoma volume (HV), hematoma enlargement, midline shift (MLS), and intraventricular hemorrhage,^3–9 and CT is the technique most frequently used to assess them. However, in the early stages, it can be difficult to monitor these radiologic features with repeat CT due to the clinical and/or hemodynamic state of the patient and the risk of radiation overexposure.Transcranial duplex sonography (TDS) is a noninvasive technique that provides simultaneous 2D imaging of brain parenchyma and hemodynamic information from the main cerebral arteries. The role of TDS is well-established in the assessment of ischemic stroke, but its usefulness in acute ICH has been reported in only a few studies.^10–15Visualization of acute ICH with TDS is feasible: The ICH can be identified as a hyperechoic mass.^10–12 Additionally, TDS allows the assessment of the third ventricle (IIIV), the lateral ventricles (LVs), MLS, and the presence of intraventricular hemorrhage.^13–16 TDS may have some potential advantages over CT, including the feasibility of performance at the bedside as many times as necessary and regardless of the hemodynamic situation of the patient. Despite a good correlation between TDS and CT having been previously reported,^10–15 the prognostic value of this technique in ICH is yet to be established.The question of whether TDS may reliably measure ICH characteristics and predict END and mortality following ICH has important implications for clinical practice and research. In the current study, we sought to determine the prognostic value of TDS in patients with acute ICH.     

CT Angiography Findings in Carotid Blowout Syndrome and Its Role as a Predictor of 1-Year Survival

BACKGROUND AND PURPOSE:Carotid blowout is a serious late complication of prior treatment of advanced head and neck cancer. We evaluate the efficacy of CTA in the diagnosis of impending carotid blowout syndrome in patients with head and neck cancer, and its capability to predict clinical outcome.MATERIALS AND METHODS:The clinical data of 29 patients with impending carotid blowout who underwent CTA were collected and analyzed. Imaging signs included tissue necrosis, exposed artery, viable perivascular tumor, pseudoaneurysm, and contrast extravasation. DSA was obtained in 20 patients. One-year outcomes were compared based on management.RESULTS:The most common CTA finding was necrosis (94%), followed by exposed artery (73%), viable tumor (67%), pseudoaneurysm (58%), and contrast extravasation (30%). Exposed artery, pseudoaneurysm, and contrast extravasation were the 3 CTA findings related to outcomes. All of the pseudoaneurysm and contrast extravasation cases were associated with an exposed artery. An exposed artery was the most important prognostic predictor and could not be diagnosed on DSA. Patients without the 3 findings on CTA (group 1) had the best survival rate at 1-year follow-up, followed by patients with the 3 findings treated immediately by permanent artery occlusion (group 2). Patients with the 3 findings who had no immediate treatment (group 3) had the worst outcomes (P < .001 in group 1 vs group 3 and group 2 vs group 3; P = .056 group 1 vs group 2).CONCLUSIONS:CTA, with its ability to diagnose an exposed artery compared with DSA, may offer important management and prognostic information in patients with impending carotid blowout.

Carotid blowout syndrome (CBS) is defined as rupture of the carotid artery and its branches and is a serious complication after treatment of advanced head and neck cancer. Potential causes of CBS include radical resection, radiation therapy and radiation necrosis, carotid exposure, wound infection, pharyngocutaneous fistula, and recurrent or persistent carcinoma.¹ The overall incidence of carotid blowout after neck dissection has been reported to be as high as 4.3%, and the risk is increased another 7.6-fold with further radiation therapy.² CBS typically occurs 2–20 years after surgery or radiation therapy,^3,4 and average estimates of cumulative neurologic morbidity and mortality are above 60% and 40%, respectively, in patients with CBS.⁵ CBS can be categorized into 1 of 3 categories: threatened, impending, and acute carotid blowout.¹ Threatened carotid blowout is defined as physical examination or imaging results that suggest inevitable hemorrhage from 1 of the carotid arteries or its branches if no action is taken. Impending carotid blowout (also called sentinel hemorrhage) is defined as transient hemorrhage that resolves spontaneously or with packing or pressure. Acute carotid blowout represents hemorrhage that cannot be controlled by packing or pressure.¹ Surgical management of carotid blowout is usually technically difficult and is associated with high morbidity and mortality rates.^1,2,6,7 After surgical ligation or permanent arterial occlusion (PAO) of the carotid artery, the incidence of immediate or delayed cerebral ischemic complications can be as high as 15%–20%.^7,8–12 The complication rate of a balloon occlusion test before PAO of the carotid artery is reported to be as high as 3.2%, and it may be even higher in fragile postirradiation vessels.¹³ Delayed ischemia after passing the balloon occlusion test is yet another concern.^10,14,15 Stent-graft deployment, with or without coiling, is another endovascular treatment of CBS. Stent-grafting can preserve the affected carotid flow but has a high rate of early and delayed complications.^16–19 No significant difference in short-term outcome between stent-graft deployment and PAO has been reported,²⁰ and long-term results have not been reported.¹⁷CTA has become widely available and is sensitive and specific in the detection of hemorrhagic vascular disorders such as aneurysms, arteriovenous malformations, dural arteriovenous fistulas, and intracranial dissections. Contrast extravasation on CTA predicts hematoma expansion, mortality, and clinical outcome in primary intracerebral hemorrhage.^21–26 To our knowledge, there have been no past reports about the use of CTA in the diagnosis of CBS or as an outcome predictor. The aim of our study was to evaluate the efficacy of CTA in the diagnosis of impending CBS, and its capability to predict clinical outcome after management.     

The Safety of Intra-arterial Tirofiban during Endovascular Therapy after Intravenous Thrombolysis

BACKGROUND AND PURPOSE:The safety and efficacy of tirofiban during endovascular therapy in patients undergoing intravenous thrombolysis with recombinant IV tPA remain unclear. This study aimed to investigate the safety and efficacy of intra-arterial tirofiban use during endovascular therapy in patients treated with IV tPA.MATERIALS AND METHODS:Using a multicenter registry, we enrolled patients with acute ischemic stroke who underwent endovascular therapy. Safety outcomes included postprocedural parenchymal hematoma type 2 and/or thick subarachnoid hemorrhage, intraventricular hemorrhage, and 3-month mortality. Efficacy outcomes included the successful reperfusion rate, postprocedural reocclusion, and good outcomes at 3 months (mRS scores of 0–2). The tirofiban effect on the outcomes was evaluated using a multivariable analysis while adjusting for potential confounders.RESULTS:Among enrolled patients, we identified 314 patients with stroke (279 and 35 patients in the no tirofiban and tirofiban groups, respectively) due to an intracranial artery occlusion who underwent endovascular therapy with intravenous thrombolysis. A multivariable analysis revealed no association of intra-arterial tirofiban with postprocedural parenchymal hematoma type and/or thick subarachnoid hemorrhage (adjusted OR, 1.07; 95% CI, 0.20–4.10; P = .918), intraventricular hemorrhage (adjusted OR, 0.43; 95% CI, 0.02–2.85; P = .467), and 3-month mortality (adjusted OR, 0.38; 95% CI, 0.04–1.87; P = .299). Intra-arterial tirofiban was not associated with good outcome (adjusted OR, 2.22; 95% CI, 0.89 –6.12; P = .099).CONCLUSIONS:Using intra-arterial tirofiban during endovascular therapy after IV tPA could be safe.

Given the positive findings of randomized controlled trials of endovascular therapy (EVT) with newer devices,^1-5 EVT has become a standard therapy for anterior circulation ischemic stroke.^2,4 Although it remains unclear whether EVT combined with intravenous thrombolysis (IVT) with tPA is better than EVT alone, the American Stroke Association/American Heart Association guidelines recommends IVT for eligible patients with large-vessel occlusion (LVO).⁶IV tPA improves outcomes in patients with acute ischemic stroke.⁷ However, given that IV tPA increases the risk of intracranial hemorrhage, it limits additional procedural techniques during EVT. A large pivotal study on EVT reported that 29% of patients lacked successful reperfusion (modified TICI [mTICI] ≧ 2b).⁸ Additionally, during EVT, endothelial damage can occur with resulting platelet activation, which causes reocclusion.⁹ This often requires rescue treatment, including balloon angioplasty, stent placement, or adjuvant thrombolytic infusion. Although antiplatelet agents or thrombolytic infusion has benefits in cases involving stent deployment or ongoing thrombus formation, these treatments may increase the risk of bleeding complications.Tirofiban is the most commonly used rescue thrombolytic.¹⁰ However, its safety and efficacy in EVT among patients with acute ischemic stroke remain unclear.^11-17 Additionally, although studies of EVT have reported that 83% of patients were treated with IV tPA before EVT,⁸ there is no evidence regarding the use of tirofiban during EVT in patients treated with IV tPA.Therefore, this study aimed to investigate the safety and efficacy of intra-arterial (IA) tirofiban during EVT in patients treated with IV tPA.     

Autosomal Dominant Polycystic Kidney Disease and Intracranial Aneurysms: Is There an Increased Risk of Treatment?

BACKGROUND AND PURPOSE:Autosomal dominant polycystic kidney disease is associated with an increased risk of intracranial aneurysms. Our purpose was to assess whether there is an increased risk during aneurysm coiling and clipping.MATERIALS AND METHODS:Data were obtained from the National Inpatient Sample (2000–2011). All subjects had an unruptured aneurysm clipped or coiled and were divided into polycystic kidney (n = 189) and control (n = 3555) groups. Primary end points included in-hospital mortality, length of stay, and total hospital charges. Secondary end points included the International Classification of Diseases, Ninth Revision codes for iatrogenic hemorrhage or infarction; intracranial hemorrhage; embolic infarction; and carotid and vertebral artery dissections.RESULTS:There was a significantly greater incidence of iatrogenic hemorrhage or infarction, embolic infarction, and carotid artery dissection in the patients with polycystic kidney disease compared with the control group after endovascular coiling. There was also a significantly greater incidence of iatrogenic hemorrhage or infarction in the polycystic kidney group after surgical clipping. However, the hospital stay was not longer in the polycystic kidney group, and the total hospital charges were not higher. Additional analysis within the polycystic kidney group revealed a significantly shorter length of stay but similar in-hospital costs when subjects underwent coiling versus clipping.CONCLUSIONS:Patients with polycystic kidney disease face an increased risk during intracranial aneurysm treatment, whether by coiling or clipping. This risk, however, does not translate into longer hospital stays or increased hospital costs. Despite the additional catheterization-related risks of dissection and embolization, coiling results in shorter hospital stays and similar mortality compared with clipping.

Autosomal dominant polycystic kidney disease (ADPCKD) is a genetic disorder affecting 1 in 1000 individuals worldwide and is associated with an increased risk of intracranial aneurysms, ranging from 4% to 23%^1–6 compared with the general population risk of 2%–3%.^7–10 Patients with ADPCKD are also at increased risk for aneurysm rupture earlier in life (mean age, 35–45 years),^1,11–13 compared with the general population (mean age, 50–54 years).^14,15There is evidence that the associated vascular defects in ADPCKD may be due to mutations in the PKD1 and PKD2 genes, located on the short arm of chromosomes 16 and 4.^16,17 Abnormalities of these genes in mouse models correspond with increased rates of arterial dissection, arterial rupture, and intracranial vascular abnormalities.¹⁸ To our knowledge, only 1 study to date has investigated whether these issues engender an increased risk when treating intracranial aneurysms (whether by endovascular coiling or surgical clipping).² The purpose of this investigation was to assess whether ADPCKD confers an increased peri- and immediate postprocedural risk of aneurysm coiling and clipping.     

Fellows' Journal Club: Interventional Stroke Therapies in the Elderly: Are We Helping?

BACKGROUND AND PURPOSE:It is unclear whether endovascular therapies for the treatment of AIS are being offered or are safe in older adults. The use and safety of endovascular interventions in patients older than 75 years of age were assessed.MATERIALS AND METHODS:A retrospective review of patients with AIS 75 years or older (n = 37/1064) was compared with a younger cohort (n = 70/1190) by using an established data base. Admission and discharge NIHSS scores, rates of endovascular treatment, SICH, in-hospital mortality, and the mBI were assessed.RESULTS:Rates of endovascular treatments were significantly lower in older patients (5.9% in the younger-than-75-year versus 3.5% in the older-than-75-year cohort, P = .007). Stroke severity as measured by the NIHSS score was equivalent in the 2 age groups. The mBI at 12 months was worse in the older patients (mild or no disability in 52% of the younger-than-75-year and 22% in the 75-year-or-older cohort, P = .006). Older patients had higher rates of SICH (9% in younger-than-75-year versus 24% in the 75-year-or-older group, P = .04) and in-hospital mortality (26% in younger-than-75-year versus 46% in the 75-year-or-older group, P = .05).CONCLUSIONS:Patients older than 75 years of age were less likely to receive endovascular treatments. Older patients had higher rates of SICH, disability, and mortality. Prospective randomized trials are needed to determine the criteria for selecting patients most likely to benefit from acute endovascular therapies.

Agrowing number of endovascular therapies are available for the treatment of AIS. These therapies offer options for patients who are outside the IV thrombolytic treatment window, have continued large-vessel occlusion, or have contraindications for IV therapies (ie, recent surgery).^1,2 AIS exerts the heaviest toll in terms of morbidity and mortality on the aged population,³ making interventions that reduce the poor outcomes in this age group valuable. Several studies evaluating the use of IV tPA in the elderly have found it to be safe and effective.^4–7 However, less information is available regarding the safety and efficacy of endovascular recanalization therapies for the acute management of AIS. Therapies including IA tPA, clot retrieval devices, and combination therapies with IV tPA have been shown to improve revascularization rates and stroke outcomes up to 6 hours after the onset of stroke in younger patients.^8–12 The higher incidence of amyloid angiopathy,¹³ decreased tPA clearance,¹⁴ difficult vascular access, polypharmacy, blood-brain barrier impairment,¹⁵ and age-related alterations in coagulation^16,17 has raised concerns of increased complications, mainly SICH, which are associated with increased mortality and disability,^18,19 when applying these treatments to the elderly. The objective of this study was to assess the complication rates and functional outcomes in older patients treated with endovascular techniques.     

Symptom Differences and Pretreatment Asymptomatic Interval Affect Outcomes of Stenting for Intracranial Atherosclerotic Disease

BACKGROUND AND PURPOSE:Different types of symptomatic intracranial stenosis may respond differently to interventional therapy. We investigated symptomatic and pathophysiologic factors that may influence clinical outcomes of patients with intracranial atherosclerotic disease who were treated with stents.MATERIALS AND METHODS:A retrospective analysis was performed of patients treated with stents for intracranial atherosclerosis at 4 centers. Patient demographics and comorbidities, lesion features, treatment features, and preprocedural and postprocedural functional status were noted. χ² univariate and multivariate logistic regression analysis was performed to assess technical results and clinical outcomes.RESULTS:One hundred forty-two lesions in 131 patients were analyzed. Lesions causing hypoperfusion ischemic symptoms were associated with fewer strokes by last contact [χ² (1, n = 63) = 5.41, P = .019]. Nonhypoperfusion lesions causing symptoms during the 14 days before treatment had more strokes by last contact [χ² (1, n = 136), 4.21, P = .047]. Patients treated with stents designed for intracranial deployment were more likely to have had a stroke by last contact (OR, 4.63; P = .032), and patients treated with percutaneous balloon angioplasty in addition to deployment of a self-expanding stent were less likely to be stroke free at point of last contact (OR, 0.60; P = .034).CONCLUSIONS:More favorable outcomes may occur after stent placement for lesions causing hypoperfusion symptoms and when delaying stent placement 7–14 days after most recent symptoms for lesions suspected to cause embolic disease or perforator ischemia. Angioplasty performed in addition to self-expanding stent deployment may lead to worse outcomes, as may use of self-expanding stents rather than balloon-mounted stents.

Intracranial atherosclerotic disease (ICAD) causes considerable morbidity and mortality, accounting for up to one-third of ischemic strokes in some series, particularly in certain populations.^1–3 Some lesions prove recalcitrant to first-line medical management, and, in recent decades, endovascular treatments have emerged and evolved as complementary therapies.^4,5 Early series demonstrated technical feasibility and acceptable safety for percutaneous transluminal angioplasty (PTA) and then stent placement of lesions in ICAD.^5–17 Initially, intracranial procedures were performed with devices designed and approved for coronary interventions, with subsequent release of angioplasty balloons specifically engineered for intracranial use.^5,12,17–33 In 2005, the Wingspan stent system with Gateway PTA balloon catheter (Stryker, Kalamazoo, Michigan) became the first stent approved for treatment of ICAD in the United States.^{5,12,18–22,25,34} Numerous studies reported progressively improved outcomes and low complication rates, but randomized data proving efficacy were lacking.^{5,12,18,20,24,25,35,36} In 2011, enrollment in the first randomized, controlled trial to evaluate stent placement versus medical management of ICAD, the Stent placement and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial, was halted early due to high complication rates in the stent placement group as compared with the medical management group.⁴The results of SAMMPRIS have elicited strong responses from both proponents and detractors of stent placement, with clinical decisions now changing.⁵ This current study retrospectively analyzes results of stent placement procedures performed for ICAD at 4 centers, with attention given to factors not specifically assessed in SAMMPRIS that may help guide further investigations of endovascular ICAD management.     

Selective-versus-Standard Poststent Dilation for Carotid Artery Disease: A Systematic Review and Meta-Analysis

BACKROUND:The safety and efficacy of standard poststent angioplasty in patients undergoing carotid artery stent placement have not been well-established.PURPOSE:We conducted a systematic review of the literature to evaluate the safety and efficacy of carotid artery stent placement and analyzed outcomes of standard-versus-selective poststent angioplasty.DATA SOURCES:A systematic search of MEDLINE, EMBASE, Scopus, and the Web of Science was performed for studies published between January 2000 and January 2015.STUDY SELECTION:We included studies with >30 patients describing standard or selective poststent angioplasty during carotid artery stent placement.DATA ANALYSIS:A random-effects meta-analysis was used to pool the following outcomes: periprocedural stroke/TIA, procedure-related neurologic/cardiovascular morbidity/mortality, bradycardia/hypotension, long-term stroke at last follow-up, long-term primary patency, and technical success.DATA SYNTHESIS:We included 87 studies with 19,684 patients with 20,378 carotid artery stenoses. There was no difference in clinical (P = .49) or angiographic outcomes (P = .93) in carotid artery stent placement treatment with selective or standard poststent balloon angioplasty. Both selective and standard poststent angioplasty groups had a very high technical success of >98% and a low procedure-related mortality of 0.9%. There were no significant differences between both groups in the incidence of restenosis (P = .93) or procedure-related complications (P = .37).LIMITATIONS:No comparison to a patient group without poststent dilation could be performed.CONCLUSIONS:Our meta-analysis demonstrated no significant difference in angiographic and clinical outcomes among series that performed standard poststent angioplasty and those that performed poststent angioplasty in only select patients.

Endovascular therapy of carotid artery disease has advanced during the past decade and is now considered a valuable treatment alternative to surgery in appropriately selected patients.^1–5 The indications for carotid endarterectomy were initially established in the North American Symptomatic Carotid Endarterectomy Trial⁶ in 1991, which expanded treatment indications to patients with symptomatic severe or moderate carotid stenoses. Formerly, patients who were not eligible for surgery were treated with percutaneous transluminal balloon angioplasty,^7,8 first described by Kerber et al in 1980.⁹ Although procedure-related complication rates were similar/comparable for both treatment modalities,^7,8,10 some potential drawbacks and specific problems occurred due to the endovascular approach, including luminal compromise from catheters and guidewires crossing the stenotic lesions and/or during balloon inflation (temporary carotid occlusion by a balloon and/or wire catheter), intraprocedural thromboembolic events, elastic vessel recoil, or intimal dissection.¹¹ After the carotid artery stent placement technique was developed, stent-assisted balloon angioplasty showed better results in event-free survival and even lower repeat angioplasty rates.¹¹ The primarily used balloon-expandable stents were increasingly replaced by self-expanding stents,^11,12 exhibiting an intrinsic radial expansion force with memory on the stenotic vessel wall. Poststent balloon angioplasty may then be performed to closely appose the stent and intima and, moreover, to expand regions of residual stent narrowing.¹¹Supporters of standard poststent balloon angioplasty (per protocol) indicated that poststent ballooning decreased the incidence of restenosis by re-establishing the normal luminal diameter. However, numerous studies^13–15 have suggested that poststent balloon dilation increases the likelihood of postprocedural emboli. Moreover, poststent ballooning can increase the probability of reflex bradycardia and hypotension, which might be associated with higher rates of periprocedural and postprocedural complications.^16–19Some authors claim that poststent dilation should be performed on a selective, case-by-case basis to maximize patient benefits and limit complications. However, to the best of our knowledge, there is no evidence in the recently published literature supporting the superiority of either of these techniques. Standard poststent balloon angioplasty has become the standard of care in many vascular centers,^20–35 and only some interventionalists^19,36–41 prefer performing poststent angioplasty on a selective base. On the basis of the latter studies, standard poststent balloon angioplasty may be associated with additional risks in patients with acceptable angiographic results, without additional post–carotid artery stent placement (CAS) angioplasty.To evaluate the safety and efficacy of standard poststent angioplasty versus selective poststent angioplasty, we conducted a systematic review and meta-analysis and analyzed outcomes by a series that performed standard poststent balloon angioplasty per protocol on all patients versus those that performed selective poststent balloon angioplasty on only a subset of patients.     

Endovascular Treatment of Anterior Communicating Artery Aneurysms: A Systematic Review and Meta-Analysis

BACKGROUND AND PURPOSE:Endovascular therapy has become an acceptable alternative to traditional clipping for the management of intracranial aneurysms. However, a limited number of studies have examined outcomes and complications specific to embolization of anterior communicating artery aneurysms.MATERIALS AND METHODS:A systematic review of the literature was conducted with the use of multiple data bases to identify reports on endovascular treatment of anterior communicating artery aneurysms between 1994 and 2012. Angiographic results, clinical outcomes, and complication rates were pooled across studies by using random-effects meta-analysis with subgroup analysis of outcomes by rupture status and time trend stratification.RESULTS:Fourteen studies, consisting of 1552 treated anterior communicating artery aneurysms, were included in this meta-analysis. The rate of immediate and long-term complete and near-complete angiographic occlusion was 88% (95% CI = 81–93%) and 85% (95% CI = 78–90%), respectively. Intraprocedural rupture rate was 4% (95% CI = 3–6%). The re-bleeding rate was 2% (95% CI = 1–4%) and the retreatment rate was 7% (95% CI = 5–12%). Morbidity or mortality caused by perioperative stroke occurred at a 3% (95% CI = 2–6%) rate. Overall procedure-related morbidity and mortality were 6% (95% CI = 4–8%) and 3% (95% CI = 2–4%), respectively. Outcomes did not differ between ruptured and unruptured aneurysms, nor did outcomes change over time, though these latter subanalyses were relatively underpowered.CONCLUSIONS:Endovascular therapy for anterior communicating artery aneurysms is associated with a high rate of complete angiographic occlusion. However, the procedure-related permanent morbidity and mortality are not negligible for aneurysms in this location.

The anterior communicating artery (AcomA) is the most common location for intracranial aneurysms in most series, and rupture of aneurysms in this location accounts for approximately 40% of aneurysmal subarachnoid hemorrhages in adults.^1–5 Aneurysms of the AcomA can be technically challenging from a surgical perspective because of complex regional flow dynamics, frequent anatomic variations, variable geometry, and the presence of critical perforators.^1,6–10 In the past 2 decades, the inherently less invasive endovascular approach has emerged as a feasible and acceptable treatment option for AcomA aneurysms.^11–14 Continual advancements in endovascular technique and adjuvant devices have led to an enlarging proportion of patients with AcomA aneurysms who are successfully treated with coil embolization.^10,11,15,16 A limited number of case series have detailed the clinical outcomes, angiographic results, and procedure-related complications specific for endovascular treatment in this location.^{10–13,15–24} We performed a systematic review of the published literature to better define safety and efficacy profiles for coil embolization of AcomA aneurysms beyond single-center experiences.     

Clinical Impact of Ventilation Duration in Patients with Stroke Undergoing Interventional Treatment under General Anesthesia: The Shorter the Better?

BACKGROUND AND PURPOSE:Whether general anesthesia for neurothrombectomy in patients with ischemic stroke has a negative impact on clinical outcome is currently under discussion. We investigated the impact of early extubation and ventilation duration in a cohort that underwent thrombectomy under general anesthesia.MATERIALS AND METHODS:We analyzed 103 consecutive patients from a prospective stroke registry. They met the following criteria: CTA-proved large-vessel occlusion in the anterior circulation, ASPECTS above 6 on presenting cranial CT, revascularization by thrombectomy with the patient under general anesthesia within 6 hours after onset of symptoms, and available functional outcome (mRS) 90 days after onset.RESULTS:The mean ventilation time was 128.07 ± 265.51 hours (median, 18.5 hours; range, 1–1244.7 hours). Prolonged ventilation was associated with pneumonia during hospitalization and unfavorable functional outcome (mRS ≥3) and death at follow-up (Mann-Whitney U test; P ≤ .001). According to receiver operating characteristic analysis, a cutoff after 24 hours predicted unfavorable functional outcome with a sensitivity and specificity of 60% and 78%, respectively. Our results imply that delayed extubation was not associated with a less favorable clinical outcome compared with immediate extubation after the procedure.CONCLUSIONS:Short ventilation times are associated with a lower pneumonia rate and more favorable clinical outcome. Cautious interpretation of our data implies that whether patients are extubated immediately after the procedure is irrelevant for clinical outcome as long as ventilation does not exceed 24 hours.

Recently, 5 prospective, randomized, open-label, blinded end point–designed clinical trials have established endovascular thrombectomy as the preferred treatment technique for acute ischemic stroke caused by large-vessel occlusion.^1–5 These studies showed that endovascular recanalization in the anterior circulation 6–8 hours after stroke onset is associated with favorable functional outcome in 33%–60% of cases (mRS ≤2 at day 90).^1–5 Basic cornerstones of the procedures such as the use of modern stent retrievers were comparable in the different studies. One controversial difference, however, was the use of intubation and general anesthesia (GA) during the procedures.^1–5 In fact, GA rates ranged from 6.7% to 37.8% in the mentioned prospective studies.^1–5 Most active members of the Society of Vascular and Interventional Neurology stated, in a recent survey, that they preferred general anesthesia over conscious sedation for recanalization treatment of acute ischemic stroke.⁶ Patients with stroke are often noncompliant during endovascular procedures.⁶ Conscious sedation and local anesthesia do not immobilize agitated patients and are not apt to secure the patient''s airway and thus may lead to aspiration.^6,7 General anesthesia and intubation, however, allow complete immobilization and comfort of the patient, thereby allowing better image quality.^7,8 On the other hand, it is assumed that delays in door-to-puncture time, development of ventilator-associated pneumonia, and ventilation-induced hypotension and hypocapnia may negatively influence clinical outcome in patients treated under GA.^9,10 In a recent retrospective study >500 patients who were treated under GA were matched with patients treated under conscious sedation.¹¹ Patients with GA were found to have a higher in-hospital mortality and higher rate of pneumonia.¹¹ However, patients were not matched for stroke severity (NIHSS scores were not reported), and this omission could account for the worse outcome.^11,12In the end, one can break the debate down to the following 2 questions: 1) Is GA per se a risk factor for unfavorable clinical outcome? 2) Are prolonged ventilation times associated with unfavorable clinical outcome? Only a prospective, randomized study can address the first question. The second question, however, can be approached by examining a cohort that was treated predominantly under GA. Given that this was the case in the patients treated in our institution, our aim was to determine whether short ventilation times and early extubation in the angiography suite are associated with a more favorable clinical outcome.     

Endovascular Treatment of Ruptured Blister-Like Aneurysms: A Systematic Review and Meta-Analysis with Focus on Deconstructive versus Reconstructive and Flow-Diverter Treatments

BACKGROUND AND PURPOSE:Various endovascular techniques have been applied to treat blister-like aneurysms. We performed a systematic review to evaluate endovascular treatment for ruptured blister-like aneurysms.MATERIALS AND METHODS:We performed a comprehensive literature search and subgroup analyses to compare deconstructive versus reconstructive techniques and flow diversion versus other reconstructive options.RESULTS:Thirty-one studies with 265 procedures for ruptured blister-like aneurysms were included. Endovascular treatment was associated with a 72.8% (95% CI, 64.2%–81.5%) mid- to long-term occlusion rate and a 19.3% (95% CI, 13.6%–25.1%) retreatment rate. Mid- to long-term neurologic outcome was good in 76.2% (95% CI, 68.9%–8.4%) of patients. Two hundred forty procedures (90.6%) were reconstructive techniques (coiling, stent-assisted coiling, overlapped stent placement, flow diversion) and 25 treatments (9.4%) were deconstructive. Deconstructive techniques had higher rates of initial complete occlusion than reconstructive techniques (77.3% versus 33.0%, P = .0003) but a higher risk for perioperative stroke (29.1% versus 5.0%, P = .04). There was no difference in good mid- to long-term neurologic outcome between groups, with 76.2% for the reconstructive group versus 79.9% for the deconstructive group (P = .30). Of 240 reconstructive procedures, 62 (25.8%) involved flow-diverter stents, with higher rates of mid- to long-term complete occlusion than other reconstructive techniques (90.8% versus 67.9%, P = .03) and a lower rate of retreatment (6.6% versus 30.7%, P < .0001).CONCLUSIONS:Endovascular treatment of ruptured blister-like aneurysms is associated with high rates of complete occlusion and good mid- to long-term neurologic outcomes in most patients. Deconstructive techniques are associated with higher occlusion rates but a higher risk of perioperative ischemic stroke. In the reconstructive group, flow diversion carries a higher level of complete occlusion and similar clinical outcomes.

Blister-like aneurysms (BLAs) are intracranial arterial lesions originating at nonbranching sites of the dorsal supraclinoid internal carotid artery and basilar artery. BLAs account for 0.3%–1% of intracranial aneurysms and 0.9%–6.5% of ruptured aneurysms.^1–6 They are attributed to subadventitial dissections resulting in a focal wall defect with absence of internal elastic lamina and media, leading, in most cases, to acute subarachnoid hemorrhage. The arterial gap is only covered with adventitia and thin fibrinous tissue.^4,7–10Ruptured BLAs have a high mortality rate. Furthermore, treatment of these lesions is technically difficult because they often lack a defined neck and the aneurysm sac has a very thin wall.^4,11–13 Thus, ruptured BLAs are associated with high rates of spontaneous or treatment-induced rebleed and death, regardless of treatment type.^2,4,13,14Many surgical techniques such as wrapping or trapping with bypass have been described for the treatment of these lesions. However, such techniques are often associated with high perioperative morbidity and mortality rates.^{8,10,11,13,15–20} Because of these results, endovascular techniques, both reconstructive and deconstructive, have emerged as the treatment of choice due to perceived lower rates of treatment-related morbidity and higher efficacy.^{2–4,12,21–25} However, because of the rarity of these lesions, most series on endovascular treatment of BLAs are small retrospective single-center case series. Thus, the efficacy and safety of endovascular treatment of these lesions have not been well-established.⁴ In addition, little is known regarding whether reconstructive techniques with parent artery preservation are associated with similar rates of angiographic occlusion and improved clinical outcomes compared with deconstructive parent artery sacrifice.¹³ Therefore, we performed a systematic review of the literature examining the overall efficacy of endovascular treatments for ruptured BLAs and comparing outcomes of reconstructive techniques such as stent placement, flow diversion, and stent-assisted coiling with deconstructive techniques such as parent artery occlusion and trapping. We also performed a subgroup analysis comparing the safety and efficacy of flow-diverter treatment with other reconstructive techniques.     

Phase White Matter Signal Abnormalities in Patients with Clinically Isolated Syndrome and Other Neurologic Disorders

BACKGROUND AND PURPOSE:Identifying MRI biomarkers that can differentiate multiple sclerosis patients from other neurological disorders is a subject of intense research. Our aim was to investigate phase WM signal abnormalities for their presence, prevalence, location, and diagnostic value among patients with clinically isolated syndrome and other neurologic disorders and age-, sex-, and group-matched healthy controls.MATERIALS AND METHODS:Forty-eight patients with clinically isolated syndrome and 30 patients with other neurologic diseases and a healthy control group (n = 47) were included in the study. Subjects were scanned at 3T by using SWI-filtered phase and T2WI, with WM signal abnormalities ≥3 mm being classified.RESULTS:Patients with clinically isolated syndrome had significantly more phase and T2 WM signal abnormalities than healthy controls (P < .001). Phase WM signal abnormalities were more prevalent among patients with clinically isolated syndrome compared with patients with other neurologic disorders (4:1 ratio), whereas T2 WM signal abnormalities were more ubiquitous with a 2:1 ratio. The presence of phase WM signal abnormalities was sensitive for clinically isolated syndrome (70.8%) and achieved a moderate-to-high specificity for differentiating patients with clinically isolated syndrome and healthy controls, patients with other neurologic disorders, and patients with other neurologic disorders of other autoimmune origin (specificity, 70%–76.7%). Combining the presence of ≥2 phase lesions with the McDonald 2005 and 2010 criteria for dissemination in space improved the specificity (90%), but not the accuracy, in differentiating patients with clinically isolated syndrome from those with other neurologic disorders. In subanalyses among patients with clinically isolated syndrome who converted to clinically definite multiple sclerosis versus those who did not within a 3-year follow-up period, converters had significantly more phase (P = .008) but not T2 or T1 WM signal abnormalities.CONCLUSIONS:Phase WM signal abnormalities are prevalent among patients with clinically isolated syndrome. The presence of (multiple) phase WM signal abnormalities tended to be more predictive of conversion to clinically definite multiple sclerosis and was specific in differentiating patients with clinically isolated syndrome and other neurologic disorders, compared with T2 WM signal abnormalities; however, the accuracy remains similar to that of the current McDonald criteria.

The occurrence of WM signal abnormalities (SAs) is a hallmark feature of multiple sclerosis, yet the clinical relevance of the pathologic substrate of WM-SAs is disappointing.^1–4 WM-SAs observed on T2WI and T1WI represent focal pathology and are thought to be caused by inflammation, edema, demyelination, or gliosis.² They are usually secondary to active inflammation, imaged by using postcontrast T1WI gadolinium-enhanced scanning.⁵ Even though T2 WM-SAs are present at the first demyelinating episode, the poor specificity of conventional MR imaging^1,6 and comparable MR imaging features at disease onset compared with ischemic, autoimmune diseases or aging limits their predictive value.Previously, differential diagnosis between MS and other conditions was considered by using brain and spinal cord MR imaging and incorporating number, location, and morphology of T2 WM-SAs in the diagnostic criteria of MS⁷ or by using different nonconventional MR imaging techniques.^6,8–10 It is important to further investigate the value of nonconventional MR imaging techniques in the MS differential diagnosis, for example by using SWI-filtered phase to identify early focal brain pathology indicative of MS, especially in patients with clinically isolated syndrome (CIS).Recent studies have confirmed histologically that WM-SAs visible on MR imaging phase and R^2* correspond to focal iron deposits, whereas T2 and T1 WM-SAs are influenced by water content.¹¹ A substantial subset of MS WM-SAs has phase shifts^11,12 and morphologic differences.^11–15 However, factors other than nonheme iron may influence the observed WM-SA signal, such as changes in myelin, deoxyhemoglobin, and inflammation.^11,16–19 Therefore, because there are a multitude of effects, it is not fully known to what extent they each individually influence SWI-filtered phase changes.Phase changes may signal early WM-SA development^17,20 in that these phase WM-SAs may appear initially but then disappear as the pathology advances.¹⁷ Considering that the distinct pathologies influencing phase shift (eg, cellular/myelin destruction, iron levels, microstructural changes) in WM-SAs are most likely intricately related and are observed in MS and related disorders,^{12,14,15,21–23} the inquiry into pathology visible on SWI-filtered phase remains important regardless of the causative factors.SWI-filtered phase work has mostly focused on patients with MS,^{11,13–15,24} high-field-strength imaging,^11,13,24 or histologically validating phase WM-SAs.^11,25 Regardless of what pathology phase WM-SAs represent, it is imperative to identify whether their presence has diagnostic value. In the present study, we assessed WM-SAs visible on T2WI and SWI-filtered phase among patients with CIS and patients with other neurologic disorders (OND) to investigate their prevalence, location, and ability to differentiate disease groups.     

Hyperintense Basilar Artery on FLAIR MR Imaging: Diagnostic Accuracy and Clinical Impact in Patients with Acute Brain Stem Stroke

BACKGROUND AND PURPOSE:FLAIR-hyperintense vessels are known to be a sign of sluggish collateral blood flow in hemispheric vessel occlusion. Additionally, they seem to have a prognostic implication. The aim of the current study was to evaluate the hyperintense configuration of the basilar artery (FLAIR-hyperintense basilar artery) as a marker of basilar artery occlusion and as a predictor of patient outcome.MATERIALS AND METHODS:We retrospectively identified 20 patients with basilar artery occlusion who initially underwent MR imaging with subsequent DSA. The diagnostic accuracy of the FLAIR-hyperintense basilar artery sign was tested by 4 independent readers in a case-control design, and the relation among FLAIR-hyperintense basilar artery and DWI posterior circulation–ASPECTS, patient outcome, and patient survival was evaluated. To grade the extent of the FLAIR-hyperintense basilar artery sign, we generated a score by counting the number of sections from the basilar tip to the foramen magnum in which a hyperintense signal in the vessel lumen was present multiplied by the section thickness.RESULTS:The FLAIR-hyperintense basilar artery sign showed moderate sensitivity (65%–95%) but very good specificity (95%–100%) and accuracy (85%–93%) for the detection of basilar artery occlusion. Substantial or excellent inter-reader agreement was observed (Cohen κ, 0.64–0.85). The FLAIR-hyperintense basilar artery inversely correlated with the posterior circulation–ASPECTS (r = −0.67, P = .01). Higher FLAIR-hyperintense basilar artery scores were associated with patient death (28.3 ± 13.7 versus 13.4 ± 11.1, P < .05).CONCLUSIONS:The FLAIR-hyperintense basilar artery sign proved to be a valuable marker of vessel occlusion and may substantially support the diagnosis of basilar artery occlusion. The established FLAIR-hyperintense basilar artery score may be helpful for the prediction of individual patient survival.

FLAIR-hyperintense vessels (FHVs) are frequently observed in the M2-to-M4 segments of patients with acute ischemic stroke of the anterior circulation. They can be an indicator of occlusion,^1,2 reversible constriction,³ or stenosis^4–6 of intra- and extracranial arteries, and they are identified as the absence of the typical “flow void” in the tortuous sulcal arteries on the cerebral surface.^2,7 It is hypothesized that the FHV sign is caused mainly by sluggish, slow blood flow and also by clot signal intensity, the latter as an effect of oxyhemoglobin.^8,9At the beginning, the FHV sign was mainly proposed as a very sensitive marker of vessel occlusion and of flow impairment in MCA stroke.^8,10–14 Publications dealing with its prognostic significance were rare^8,15 until Lee et al,¹ in 2009, observed a relation between the extent of the FHV and the amount of diffusion-perfusion mismatch in patients with MCA occlusions. They suggested that the FHV is an indicator of collateral flow besides its proved sensitivity for mere blood flow alterations. Since then, there have been several original studies^{3,5,7,16–22} and 1 review² addressing the potential role of the FHV sign as an imaging biomarker of collateral circulation and as a predictor of patient outcome. Although some patients with basilar artery occlusion (BAO) in the low single-digit range were included in a few studies dealing with the diagnostic significance of the FHV sign,^10,12,14 the focus of these investigations has been on patients with MCA stroke. To date, neither the diagnostic nor the prognostic value of the FLAIR-hyperintense basilar artery (FHBA) sign has been investigated in a dedicated study, to our knowledge.     

Vision Outcomes and Major Complications after Endovascular Coil Embolization of Ophthalmic Segment Aneurysms

BACKGROUND AND PURPOSE:As aneurysms arising from the ophthalmic segment of the internal carotid artery increase in size, they can compress the optic nerve, prompting patients to present with visual disturbances. The purpose of this article is to describe the clinical and angiographic results with an emphasis on visual outcomes following the endovascular treatment of ophthalmic segment ICA aneurysms.MATERIALS AND METHODS:The records of 1254 patients who presented for endovascular treatment of a cerebral aneurysm were retrospectively reviewed to identify 65 consecutive patients who underwent coil embolization of an ophthalmic segment ICA aneurysm. The clinical records, treatment reports, and imaging were reviewed with a focus on visual outcomes.RESULTS:Twenty-two of the 65 patients (34%) who presented for treatment of an ophthalmic aneurysm reported a visual disturbance at presentation. Fifteen of the 22 patients (68%) experienced an improvement in their symptoms after treatment. Overall, patients with visual symptoms were significantly more likely to benefit from treatment than to have a decline in vision (P = .03). The overall morbidity was 4%, and mortality was 0%. The retreatment rate was high at 30%, though this was disproportionately weighted by an 86% retreatment rate in patients with ruptured aneurysms.CONCLUSIONS:Patients with visual symptoms attributable to ophthalmic segment ICA aneurysms undergoing endovascular coil embolization were statistically more likely to experience an improvement in their vision than to have worsening or unchanged vision. Coiling was associated with a low morbidity rate, though an elevated retreatment rate.

Aneurysms arising from the ophthalmic segment of the internal carotid artery account for approximately 5% of all intracranial aneurysms.^1,2 As these aneurysms increase in size, they can compress the optic nerve, prompting the patient to present with visual disturbances, often involving the inferior and/or nasal fields first.^2,3 Both surgical and endovascular treatment of these aneurysms have shown the potential to improve visual disturbances if occurring early.^2,4–11 However, treatment of these aneurysms is not without its own set of inherent risks. Retinal artery occlusion or delayed optic ischemia may occur after either surgical or endovascular repair.^12–14 A review of recent surgical literature suggests a permanent morbidity ranging from 3% to 38% following treatment of an ophthalmic segment ICA aneurysm.^{3,5,6,10,15–18} This morbidity includes a risk of new or worsened visual disturbance in 2%–30% of surgically treated patients and 3%–8% of endovascularly treated patients.^3,5,6,15,16This article assesses the angiographic and clinical outcomes of 65 consecutive patients who presented for initial treatment of an ophthalmic segment ICA aneurysm via an endovascular approach. Our goal is to describe the clinical and angiographic outcomes with an emphasis on visual outcomes following the endovascular treatment of ophthalmic segment aneurysms.     

Cortical Activation Through Passive-Motion Functional MRI

BACKGROUND AND PURPOSE:Functional brain mapping is an important technique for neurosurgical planning, particularly for patients with tumors or epilepsy; however, mapping has traditionally involved invasive techniques. Existing noninvasive techniques require patient compliance and may not be suitable for young children. We performed a retrospective review of our experience with passive-motion functional MR imaging in anesthetized patients to determine the diagnostic yield of this technique.MATERIALS AND METHODS:A retrospective review of patients undergoing passive-motion fMRI under general anesthesia at a single institution over a 2.5-year period was performed. Clinical records were evaluated to determine the indication for fMRI, the ability to detect cortical activation, and, if present, the location of cortical activation.RESULTS:We identified 62 studies in 56 patients in this time period. The most common indication for fMRI was epilepsy/seizures. Passive-motion fMRI identified upper-extremity cortical activation in 105 of 119 (88%) limbs evaluated, of which 90 (86%) activations were in an orthotopic location. Lower-extremity cortical activation was identified in 86 of 118 (73%) limbs evaluated, of which 73 (85%) activations were in an orthotopic location.CONCLUSIONS:Passive-motion fMRI was successful in identifying cortical activation in most of the patients. This tool can be implemented easily and can aid in surgical planning for children with tumors or candidates for epilepsy surgery, particularly those who may be too young to comply with existing noninvasive functional measures.

The criterion standard for presurgical brain mapping has typically been intraoperative cortical stimulation mapping and the Wada test.^1–4 Both methods are invasive procedures, and their efficacy and superiority over other mapping procedures have become less clear with advances in noninvasive brain-mapping techniques,^4–12 with some studies showing that these alternative methods are comparable to stand-alone and/or adjunct techniques.^9–18 Blood oxygen level–dependent functional MR imaging is an increasingly used imaging technique in the clinical setting. Since the early 1990s, it has been used to study brain function in healthy individuals and particularly for surgical planning in patients with brain tumors or epilepsy.^{2,4,17,19–22} This imaging technique maps areas of cortical activation via changes in blood flow to metabolically active brain regions during cortical activation, typically secondary to specific motor, language, and visual tasks. fMRI provides a number of benefits: it is noninvasive, it is a useful tool for presurgical evaluation for invasive procedures that involve high risk,^{2,4,17,19,20,23,24} and it can also assess the current function of patients with brain lesions or previous brain surgery.^20,25 Clinically, it is performed as a task-based technique that requires the patient to cooperate and keep all other body movements to a minimum. Incomplete compliance limits the utility of this technology and introduces risk for spurious results. Compliance with the tasks and remaining still is a particular concern in young children and patients with developmental or acquired cognitive deficits.^26,27 Even children who can perform the task during training sessions may not be able to comply in the MR imaging scanner.²⁷A strategy that allows this information to be obtained from subjects who are unable to cooperate is to perform a similar fMRI task under sedation. fMRI of sedated patients performed with passive motion of the extremities has been successful in some reports.^{15,23,24,28,29} The goal is to map the motor cortex while removing the need for task compliance and reducing or eliminating concerns for patient motion.^23,24,28 We performed a retrospective review of our institution''s 2.5-year experience with passive-motion fMRI to assess the feasibility and reliability of this imaging technique.     

Outcomes Are Not Different between Patients with Intermediate and High DWI-ASPECTS after Stent-Retriever Embolectomy for Acute Anterior Circulation Stroke

BACKGROUND AND PURPOSE:Questions remain as to what benefits embolectomy provides to patients presented with considerable early ischemic changes on baseline imaging studies. This study aimed to investigate the impact of the Alberta Stroke Program Early CT Score applied to DWI on treatment outcomes in patients with acute stroke undergoing stent-retriever embolectomy.MATERIALS AND METHODS:We retrospectively analyzed the clinical and DWI data from 171 patients with acute anterior circulation stroke who were treated with stent-retriever embolectomy within 6 hours of symptom onset. DWI-ASPECTS scores were analyzed with the full scale or were dichotomized (4–6 versus 7–10). Patients with DWI-ASPECTS ≤3 were excluded from the study. Associations between outcome and clinical and radiologic factors were determined with a multivariate logistic regression analysis. A good outcome was defined as a modified Rankin Scale score of 0–2 at 3 months.RESULTS:The median DWI-ASPECTS was 7 (interquartile range, 6–8). The rates of good outcome, symptomatic hemorrhage, and mortality were not different between high DWI-ASPECTS (scores of 7–10) and intermediate DWI-ASPECTS (scores of 4–6) groups. In patients with an intermediate DWI-ASPECTS, good outcome was achieved in 46.5% (20/43) of patients with successful revascularization, whereas no patients without successful revascularization had a good outcome (P = .016). In multivariate logistic regression analysis, independent predictors of good outcome were age and successful revascularization.CONCLUSIONS:Our study suggested that there were no differences in outcomes between patients with a high DWI-ASPECTS and those with an intermediate DWI-ASPECTS who underwent stent-retriever embolectomy for acute anterior circulation stroke. Thus, patients with an intermediate DWI-ASPECTS otherwise eligible for endovascular therapy may not be excluded from stent-retriever embolectomy or stroke trials.

Recent randomized controlled trials have shown that stent-retriever embolectomy in addition to standard care was associated with improved functional outcome in patients with acute anterior circulation stroke due to large-vessel occlusion within 6–8 hours of symptom onset.^1–5 For further advancement in treating acute anterior circulation stroke, it is becoming important to more clearly refine the selection criteria for stent-retriever embolectomy. Several clinical and imaging factors are known to be associated with functional outcomes after endovascular treatment for acute anterior circulation stroke.^6–9 However, questions remain as to what benefits embolectomy provides to patients who present at extended time periods or those with considerable early ischemic changes on baseline imaging studies. Furthermore, the imaging technique that best determines candidacy for embolectomy in these patients remains unknown.ASPECTS is a 10-point semiquantitative scoring system, which was developed to offer the simplicity and reliability of CT to assess early ischemic changes in patients with acute ischemic stroke in the anterior circulation.¹⁰ ASPECTS has recently been applied to DWI, which is much more sensitive and accurate in the detection of acute infarction than noncontrast CT.^11–14 A recent study showed that interrater agreement for DWI-ASPECTS was superior to that for CT-ASPECTS and that DWI-ASPECTS outperformed CT-ASPECTS in predicting functional outcome at 90 days.⁹ The DWI-ASPECTS can also provide similar risk assessment far more rapidly than measurement of the infarct volume on DWI, an independent predictable marker of the clinical outcome, in patients with anterior circulation stroke.^9,15–17 However, few studies have investigated the association between pretreatment DWI-ASPECTS and functional outcome after stent-retriever embolectomy in patients with acute anterior circulation stroke.^9,14,18Although several studies showed that a DWI-ASPECTS of 7 was the optimal cutoff value for predicting clinical outcomes in patients undergoing intra-arterial or IV pharmacologic thrombolysis,^19–21 results of recent studies have suggested that some patients with a DWI-ASPECTS of <7 may still benefit from complete recanalization.¹⁴ Successful revascularization can be achieved more frequently by using stent-based embolectomy than by using pharmacologic thrombolysis or other mechanical devices.^1–5 In this context, patients with acute stroke and a DWI-ASPECTS of <7 might have a similar chance of a good outcome compared with those with a higher DWI-ASPECTS if they are treated with stent-retriever embolectomy in a short time window. However, this hypothesis has not been tested. Thus, this study aimed to investigate the impact of DWI-ASPECTS on functional outcome in patients with acute anterior circulation stroke who underwent stent-retriever embolectomy.     

Gray Matter Volume Reduction Is Associated with Cognitive Impairment in Neuromyelitis Optica

BACKGROUND AND PURPOSE:Whether gray matter impairment occurs in neuromyelitis optica is a matter of ongoing debate, and the association of gray matter impairment with cognitive deficits remains largely unknown. The purpose of this study was to investigate gray matter volume reductions and their association with cognitive decline in patients with neuromyelitis optica.MATERIALS AND METHODS:This study included 50 patients with neuromyelitis optica and 50 sex-, age-, handedness-, and education-matched healthy subjects who underwent high-resolution structural MR imaging examinations and a battery of cognitive assessments. Gray matter volume and cognitive differences were compared between the 2 groups. The correlations of the regional gray matter volume with cognitive scores and clinical variables were explored in the patients with neuromyelitis optica.RESULTS:Compared with healthy controls (635.9 ± 51.18 mL), patients with neuromyelitis optica (602.8 ± 51.03 mL) had a 5.21% decrease in the mean gray matter volume of the whole brain (P < .001). The significant gray matter volume reduction in neuromyelitis optica affected the frontal and temporal cortices and the right thalamus (false discovery rate correction, P < .05). The regional gray matter volumes in the frontal and temporal cortices were negatively correlated with disease severity in patients with neuromyelitis optica (Alphasim correction, P < .05). Patients with neuromyelitis optica had impairments in memory, information processing speed, and verbal fluency (P < .05), which were correlated with gray matter volume reductions in the medial prefrontal cortex and thalamus (Alphasim correction, P < .05).CONCLUSIONS:Gray matter volume reduction is present in patients with neuromyelitis optica and is associated with cognitive impairment and disease severity in this group.

Neuromyelitis optica (NMO) is an idiopathic, severe, demyelinating disease of the central nervous system that is characterized by optic neuritis and myelitis.^1,2 Although the brain is traditionally considered to be spared in NMO,³ recent studies have identified brain lesions in 60% of patients with this condition.⁴ In 10% of patients with NMO, the site of brain lesions on MR imaging coincides with high concentrations of the water channel aquaporin 4,^5,6 the target of NMO immunoglobulin G (NMO-IgG).Although several investigations have revealed gray matter impairment in NMO by comparing intergroup differences in the regional homogeneity,⁷ amplitude of low-frequency fluctuation,⁸ diffusivity,^9–11 perfusion,¹² and magnetization transfer ratio,¹³ whether GM structural impairment is a feature of NMO is an ongoing debate. Several studies have identified reductions in GM volume (GMV)^14–16 or cortical thickness¹⁷ in patients with NMO; however, 3 additional studies have failed to demonstrate reductions in the GMV^18,19 or cortical thickness in patients.²⁰ These conflicting outcomes may result from the low statistical power of the relatively small sample sizes (15–30 patients with NMO in previous studies). Studies with a large sample of patients with NMO may help clarify this issue.Cognitive impairment has been repeatedly reported in patients with NMO^{10,17,18,21–24} and is characterized by deficits in multiple cognitive domains, including memory, attention, and speed of information processing. The neural correlates of the cognitive impairment in NMO have been attributed to focal reductions in white matter volume and integrity.^10,18 A recent study found no correlation between cognitive impairment and cortical thinning in 23 patients with NMO.¹⁷ However, it remains unknown whether GMV reduction is associated with cognitive impairment in these patients.By recruiting a large sample of patients with NMO (n = 50), we aimed to clarify the GMV changes in NMO and the correlations of GMV changes with cognitive impairment and clinical variables in these patients.     

Progression of Microstructural Damage in Spinocerebellar Ataxia Type 2: A Longitudinal DTI Study

BACKGROUND AND PURPOSE:The ability of DTI to track the progression of microstructural damage in patients with inherited ataxias has not been explored so far. We performed a longitudinal DTI study in patients with spinocerebellar ataxia type 2.MATERIALS AND METHODS:Ten patients with spinocerebellar ataxia type 2 and 16 healthy age-matched controls were examined twice with DTI (mean time between scans, 3.6 years [patients] and 3.3 years [controls]) on the same 1.5T MR scanner. Using tract-based spatial statistics, we analyzed changes in DTI-derived indices: mean diffusivity, axial diffusivity, radial diffusivity, fractional anisotropy, and mode of anisotropy.RESULTS:At baseline, the patients with spinocerebellar ataxia type 2, as compared with controls, showed numerous WM tracts with significantly increased mean diffusivity, axial diffusivity, and radial diffusivity and decreased fractional anisotropy and mode of anisotropy in the brain stem, cerebellar peduncles, cerebellum, cerebral hemisphere WM, corpus callosum, and thalami. Longitudinal analysis revealed changes in axial diffusivity and mode of anisotropy in patients with spinocerebellar ataxia type 2 that were significantly different than those in the controls. In patients with spinocerebellar ataxia type 2, axial diffusivity was increased in WM tracts of the right cerebral hemisphere and the corpus callosum, and the mode of anisotropy was extensively decreased in hemispheric cerebral WM, corpus callosum, internal capsules, cerebral peduncles, pons and left cerebellar peduncles, and WM of the left paramedian vermis. There was no correlation between the progression of changes in DTI-derived indices and clinical deterioration.CONCLUSIONS:DTI can reveal the progression of microstructural damage of WM fibers in the brains of patients with spinocerebellar ataxia type 2, and mode of anisotropy seems particularly sensitive to such changes. These results support the potential of DTI-derived indices as biomarkers of disease progression.

Spinocerebellar ataxia type 2 (SCA2) is the second most frequent autosomal dominant inherited ataxia worldwide, after SCA3.¹ It is caused by expansion in excess of 32 CAG repeats in the gene encoding the Ataxin-2 protein, which mainly targets several pontine neurons and Purkinje cells in the cerebellum,² and it is associated with a pathologic pattern of pontocerebellar atrophy.^1,3 MR T1-weighted imaging enables in vivo detection of brain stem and cerebellar atrophy in patients with SCA2 in cross-sectional^4–6 and longitudinal⁷ studies.Recently, DWI and DTI have enabled quantitative assessment of the microstructural changes in brain tissue that result from neurodegenerative diseases.^5,8–21 In particular, in longitudinal studies, DTI may be a sensitive instrument for tracking the progression of neurodegeneration (namely, neuronal damage and loss, Wallerian degeneration, demyelination, and gliosis) and, we hope, for detecting the efficacy (or lack of thereof) of new therapeutic strategies. So far, relatively few studies have addressed this point,^22–30 and none have addressed it in relation to autosomal dominant ataxias.We performed a longitudinal DTI study in 10 patients with SCA2 and 16 age-matched healthy controls to explore the ability of DTI to detect and map the progression of microstructural damage reflecting advance of neurodegeneration. In particular, we analyzed several DTI-derived indices, including mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), fractional anisotropy (FA), and mode of anisotropy (MO), by using tract-based spatial statistics (TBSS), which enable a robust and unbiased voxelwise whole-brain analysis of the main white matter tracts.^19,21,31,32     

T1 Signal Measurements in Pediatric Brain: Findings after Multiple Exposures to Gadobenate Dimeglumine for Imaging of Nonneurologic Disease

BACKGROUND AND PURPOSE:Signal intensity increases possibly suggestive of gadolinium retention have recently been reported on unenhanced T1-weighted images of the pediatric brain following multiple exposures to gadolinium-based MR contrast agents. Our aim was to determine whether T1 signal changes suggestive of gadolinium deposition occur in the brains of pediatric nonneurologic patients after multiple exposures to gadobenate dimeglumine.MATERIALS AND METHODS:Thirty-four nonneurologic patients (group 1; 17 males/17 females; mean age, 7.18 years) who received between 5 and 15 injections (mean, 7.8 injections) of 0.05 mmol/kg of gadobenate during a mean of 2.24 years were compared with 24 control patients (group 2; 16 males/8 females; mean age, 8.78 years) who had never received gadolinium-based contrast agents. Exposure to gadobenate was for diagnosis and therapy monitoring. Five blinded readers independently determined the signal intensity at ROIs in the dentate nucleus, globus pallidus, pons, and thalamus on unenhanced T1-weighted spin-echo images from both groups. Unpaired t tests were used to compare signal-intensity values and dentate nucleus–pons and globus pallidus–thalamus signal-intensity ratios between groups 1 and 2.RESULTS:Mean signal-intensity values in the dentate nucleus, globus pallidus, pons, and thalamus of gadobenate-exposed patients ranged from 366.4 to 389.2, 360.5 to 392.9, 370.5 to 374.9, and 356.9 to 371.0, respectively. Corresponding values in gadolinium-based contrast agent–naïve subjects were not significantly different (P > .05). Similarly, no significant differences were noted by any reader for comparisons of the dentate nucleus–pons signal-intensity ratios. One reader noted a difference in the mean globus pallidus–thalamus signal-intensity ratios (1.06 ± 0.006 versus 1.02 ± 0.009, P = .002), but this reflected nonsignificantly higher T1 signal in the thalamus of control subjects. The number of exposures and the interval between the first and last exposures did not influence signal-intensity values.CONCLUSIONS:Signal-intensity increases potentially indicative of gadolinium deposition are not seen in pediatric nonneurologic patients after multiple exposures to low-dose gadobenate.

Recent reports have detailed high signal intensity (SI) in certain brain areas (primarily the dentate nucleus [DN] and globus pallidus [GP]) on unenhanced T1-weighted images following multiple exposures to gadolinium-based contrast agents (GBCAs).^1–20 Many of these reports have focused on apparent differences between macrocyclic and open-chain “linear” GBCAs,^4–13 invariably associating progressive T1 hyperintensity with multiple exposures to linear GBCAs and concluding that observed T1 signal reflects the lower stability of these agents and thus a greater propensity for gadolinium (Gd) release and, subsequently, deposition in the brain. Among the more recent reports are several that describe retrospective assessments in pediatric patients.^15–19 Although each patient evaluated received just 1 specific linear GBCA (gadopentetate dimeglumine; Magnevist; Bayer HealthCare, Wayne, New Jersey), the study-based recommendations in each case were to consider carefully the use of all linear agents in pediatric subjects.Gadobenate dimeglumine (MultiHance; Bracco Diagnostics, Monroe, New Jersey) is an ionic open-chain, linear GBCA that differs fundamentally from gadopentetate and other extracellular GBCAs in having an aromatic substituent on the chelating molecule.²¹ Unique properties conferred by this substituent include increased R1-relaxivity,²² which permits the acquisition of diagnostically valid images with a reduced dose,²³ and liver-specificity, which permits gadobenate use for hepatobiliary-phase liver applications.²⁴ An additional benefit is increased molecular stability compared with gadopentetate, other linear agents, and certain macrocyclic agents.²⁵ Studies that have evaluated brain T1 signal intensities after multiple exposures to gadobenate have yielded conflicting results with one report demonstrating T1 signal increases, albeit to a lesser extent than with gadopentetate,¹⁰ and others demonstrating no direct changes.^11,12We aimed to determine whether multiple exposures to low-dose gadobenate for nonneurologic pathology results in T1 signal changes in the DN and GP of pediatric patients relative to that in age- and weight-matched GBCA-naïve control subjects.