Bryan Yoo

M2 occlusions as targets for endovascular therapy: comprehensive analysis of diffusion/perfusion MRI, angiography, and clinical outcomes

Background The ideal population of patients for endovascular therapy (ET) in acute ischemic stroke remains undefined. Recent ET trials have moved towards selecting patients with proximal middle cerebral artery (MCA) or internal carotid artery occlusions, which will likely leave a gap in our understanding of the treatment outcomes of M2 occlusions. Objective and methods To examine the presentation, treatment, and outcomes of M2 compared with M1 MCA occlusions in patients undergoing ET by assessing comprehensive MRI, angiography, and clinical data. Results We found that M2 occlusions can lead to massive strokes defined by hypoperfused and infarcted volumes as well as death or moderate to severe disability in nearly 50% of patients at discharge. Compared with M1 occlusions, M2 occlusions achieved similar Thrombolysis in Cerebral Infarction (TICI) 2b/3 recanalization rates, with significantly less hemorrhage. M2 occlusions presented with smaller infarct and hypoperfused volumes and had smaller final infarct volumes regardless of recanalization. TICI 2b/3 recanalization of M2 occlusions was associated with smaller infarct volumes compared with TICI 0–2a recanalization, as well as less infarct expansion, in patients who received IV tissue plasminogen activator as well as those that did not. Successful reperfusion of M2 occlusions was associated with improved discharge modified Rankin scale. Conclusions If suitable as targets of ET, M2 occlusions should be given the same consideration as M1 occlusions.

Postischemic hyperperfusion on arterial spin labeled perfusion MRI is linked to hemorrhagic transformation in stroke

The purpose of this study was to investigate the relationship between hyperperfusion and hemorrhagic transformation (HT) in acute ischemic stroke (AIS). Pseudo-continuous arterial spin labeling (ASL) with background suppressed 3D GRASE was performed during routine clinical magnetic resonance imaging (MRI) on AIS patients at various time points. Arterial spin labeling cerebral blood flow (CBF) maps were visually inspected for the presence of hyperperfusion. Hemorrhagic transformation was followed during hospitalization and was graded on gradient recalled echo (GRE) scans into hemorrhagic infarction (HI) and parenchymal hematoma (PH). A total of 361 ASL scans were collected from 221 consecutive patients with middle cerebral artery stroke from May 2010 to September 2013. Hyperperfusion was more frequently detected posttreatment (odds ratio (OR)=4.8, 95% confidence interval (CI) 2.5 to 8.9, P<0.001) and with high National Institutes of Health Stroke Scale (NIHSS) scores at admission (P<0.001). There was a significant association between having hyperperfusion at any time point and HT (OR=3.5, 95% CI 2.0 to 6.3, P<0.001). There was a positive relationship between the grade of HT and time—hyperperfusion with the Spearmans rank correlation of 0.44 (P=0.003). Arterial spin labeling hyperperfusion may provide an imaging marker of HT, which may guide the management of AIS patients post tissue-type plasminogen activator (tPA) and/or endovascular treatments. Late hyperperfusion should be given more attention to prevent high-grade HT.

Molecular Disorganization of Axons Adjacent to Human Cortical Microinfarcts

Cortical microinfarcts (CMIs) are microscopically identified wedge-shaped ischemic lesions that occur at or near the cortical surface and result from occlusion of penetrating arterioles. These microscopic lesions can be observed with high-resolution magnetic resonance imaging in aging brains and in patients with cerebrovascular disease. Recent studies have suggested that strategically located microinfarcts strongly correlate with cognitive deficits, which can contribute to Alzheimer’s disease as well as other forms of dementia. We have recently shown that the molecular organization of axons into functional microdomains is altered in areas adjacent to white matter lacunar and microinfarcts, creating a peri-infarct penumbral injury in surviving axons. Whether similar changes in nodal, adjacent paranodal, and proximal axon initial segment molecular organization occur in the cortex adjacent to human CMIs is not known. Paraffin-embedded sections of autopsy brain tissue from five patients with CMIs were immunofluorescently labeled for nodal and paranodal markers including beta-IV spectrin, ankyrin-G, and contactin-associated protein. High magnification images from the peri-infarct cortical tissue were generated using confocal microscopy. In surviving cortical tissue adjacent to microinfarcts, we observed a dramatic loss of axon initial segments, suggesting that neuronal firing capacity in adjacent cortical tissue is likely compromised. The number of identifiable nodal/paranodal complexes in surviving cortical tissue is reduced adjacent to microinfarcts, while the average paranodal length is increased indicating a breakdown of axoglial contact. This axonal microdomain disorganization occurs in the relative absence of changes in the structural integrity of myelinated axons as measured by myelin basic protein and neurofilament staining. These findings indicate that the molecular organization of surviving axons adjacent to human CMIs is abnormal, reflecting lost axoglial contact and the functional elements necessary for neural transmission. This study provides support for the concept of a microinfarct penumbral injury that may account for the cumulative cognitive effect of these tiny strokes.

Multi-delay ASL can identify leptomeningeal collateral perfusion in endovascular therapy of ischemic stroke

Background and Purpose Multi-delay arterial spin-labeling (ASL) perfusion imaging has been used as a promising modality to evaluate cerebral perfusion. Our aim was to assess the association of leptomeningeal collateral perfusion scores based on ASL parameters with outcome of endovascular treatment in patients with acute ischemic stroke (AIS) in the middle cerebral artery (MCA) territory. Materials and Methods ASL data at 4 post-labeling delay (PLD) times (PLD = 1.5, 2, 2.5, 3 s) were acquired during routine clinical magnetic resonance examination on AIS patients prior to endovascular treatment. A 3-point scale of leptomeningeal collateral perfusion grade on 10 anatomic regions was determined based on arterial transit times (ATT), cerebral blood flow (CBF), and arterial cerebral blood volume (CBV), estimated by the multi-delay ASL protocol. Based on a 90-day modified Rankin Scale (mRS), the patients were dichotomized to moderate/good (mRS 03) and poor outcome (mRS 46) and the regional collateral flow scores were compared. Results Fifty-five AIS patients with unilateral MCA stroke (mean 73.9514.82 years) including 23 males were enrolled. Compared with poor outcome patients, patients with moderate to good outcomes had a significantly higher leptomeningeal collateral perfusion scores on CBV (3.012.11 vs. 1.821.51, p=0.024) but no differences on scores on CBF (2.311.61 vs. 1.661.32, p=0.231) and ATT (2.672.33 vs. 3.423.37, p=0.593). Conclusions Higher leptomeningeal collateral perfusion scores on CBV images by ASL may be a specific marker of clinical outcome after endovascular treatment in patients with acute MCA ischemic stroke. Further study with larger sample size is warranted.

DWI Lesion Patterns Predict Outcome in Stroke Patients with Thrombolysis.

Background: Lesion patterns may predict prognosis after acute ischemic stroke within the middle cerebral artery (MCA) territory; yet it remains unclear whether such imaging prognostic factors are related to patient outcome after intravenous thrombolysis. Aims: The aim of this study is to investigate the clinical outcome after intravenous thrombolysis in acute MCA ischemic strokes with respect to diffusion-weighted imaging (DWI) lesion patterns. Methods: Consecutive acute ischemic stroke cases of the MCA territory treated over a 7-year period were retrospectively analyzed. All acute MCA stroke patients underwent a MRI scan before intravenous thrombolytic therapy was included. DWI lesions were divided into 6 patterns (territorial, other cortical, small superficial, internal border zone, small deep, and other deep infarcts). Lesion volumes were measured by dedicated imaging processing software. Favorable outcome was defined as modified Rankin scale (mRS) of 0-2 at 90 days. Results: Among the 172 patients included in our study, 75 (43.6%) were observed to have territorial infarct patterns or other deep infarct patterns. These patients also had higher baseline NIHSS score (p < 0.001), a higher proportion of large cerebral artery occlusions (p < 0.001) and larger infarct volume (p < 0.001). Favorable outcome (mRS 0-2) was achieved in 89 patients (51.7%). After multivariable analysis, groups with specific lesion patterns, including territorial infarct and other deep infarct pattern, were independently associated with favorable outcome (OR 0.40; 95% CI 0.16-0.99; p = 0.047). Conclusions: Specific lesion patterns predict differential outcome after intravenous thrombolysis therapy in acute MCA stroke patients.

ASPECTS-based reperfusion status on arterial spin labeling is associated with clinical outcome in acute ischemic stroke patients:

The purpose of this study was to develop and evaluate a scoring system for assessing reperfusion status based on arterial spin labeled (ASL) perfusion MRI in acute ischemic stroke (AIS) patients receiving thrombolysis and/or endovascular treatment. Pseudo-continuous ASL with background suppressed 3D GRASE was acquired along with DWI in 90 patients within 24 h post-treatment. An automatic reperfusion scoring system (auto-RPS) was devised based on the Alberta Stroke Program Early CT Score (ASPECTS) template, and compared with manual RPS and DWI-ASPECTS. TICI (thrombolysis in cerebral infarction) scores were graded in 48 patients who received endovascular treatment. Favorable outcomes were defined by a modified Rankin Scale score of 0–2 at three months. Auto-RPS was positively correlated with DWI-ASPECTS (ρ = 0.6, P < 0.001) and was on average 1 point lower than DWI-ASPECTS (P < 0.001). The area under the receiver operating characteristic curve for discriminating poor functional outcome (n = 90) was 0.75 (95% CI, 0.64–0.86) for manual RPS, 0.85 (95% CI, 0.76–0.94) for auto-RPS, and 0.81 (95% CI, 0.71–0.90) for DWI-ASPECTS. Multiple logistic regression analysis in the TICI-graded patients (n = 48) showed that auto-RPS is highly associated with functional outcome (OR = 25.2, 95% CI 4.02–496, P < 0.01). Post treatment auto-RPS within 24 h provides a useful tool to predict functional outcome in AIS patients.

A review of the diagnosis and management of vertebral basilar (posterior) circulation disease

We have reviewed the English literature published in the last 70 years on Diseases of the Vertebral Basilar Circulation, or Posterior Circulation Disease (PCD). We have found that errors have been made in the conduct and interpretation of these studies that have led to incorrect approaches to the management of PCD. Because of the difficulty in evaluating the PC, the management of PCD has been incorrectly applied from anterior circulation disease (ACD) experience to PCD. PCD is a common form of stroke affecting 20-40% patients with stroke. Yet, the evidence is strong that the Anterior Circulation (AC) and Posterior Circulations (PC) differ in their pathology, in their clinical presentations, in the rapidity of development of symptoms, in optimal imaging methods, and in available treatments. There appears to be two categories of patients who present with PCD. The first, acute basilar artery occlusion has a more rapid onset. The diagnosis must be made quickly and if imaging proves a diagnosis of Basilar Artery Occlusion (BAO), the treatment of choice is Interventional removal of the basilar artery thrombosis or embolus. The second category of PCD and the most commonly seen PCD disease process presents with non-specific symptoms and early warnings of PCD that now can be related to ischemic events in the entire PC vessels. These warning symptoms and signs occur much earlier than those in the AC. IA angiography is still the gold standard of diagnosis and is superior in definition to MR and CT angiography which are commonly used as a convenient screening imaging tool to evaluate PCD but are both inferior to IA angiography in definition for lesions below 3-4 mm. In at least two reported studies 7T MR angiography appears superior to other imaging modalities and will become the gold standard of imaging of PCD in the future. Medical treatments applied to the ACD have not been proven of value in specific forms of PCD. Interventional therapy was promising but of unproven value in Randomized Controlled Trials (RCT) except for the treatment of Basilar Artery Occlusion (BAO). Surgical revascularization has been proved to be highly successful in patients, who are refractory to medical therapy. These studies have been ignored by the scientific community basically because of an incorrect interpretation of the flawed EC-IC Bypass Trial in 1985 as applying to all stroke patients. Moreover, the EC-IC Bypass Study did not include PCD patients in their study population, but the study results were extrapolated to patients with PCD without any scientific basis. This experience led clinicians to an incorrect bias that surgical treatments are of no value in PCD. Thus, incorrectly, surgical treatments of PCD have not been considered among the therapeutic possibilities for PCD. QMRA is a new quantitative MR technique that measures specific blood flow in extra and intracranial vessels. QMRA has been used to select those patients who may benefit from medical, or interventional, or surgical treatment for PCD based on flow determinations with a high success rate. QMRA accurately predicts the flows in many large and small vessels in the PC and AC and clearly indicates that both circulations are intimately related. From medical and surgical studies, the longer one waits for surgical treatment the higher the risk of a poor outcome results. This observation becomes obvious when the rapidity of development of PCD is compared with ACD. Recent advances in endovascular therapy in the treatment of acute basilar thrombosis is a clear sign that early diagnosis and treatment of PCD will reduce the morbidity and mortality of these diseases. In this review it is evident that there are multiple medical and surgical treatments for PCD depending upon the location of the lesion(s) and the collateral circulation demonstrated. It is clear that the AC and PC have significant differences. With the exception of the large population studies from Oxford England, the reported studies on the management of PCD in the literature represent small selected subsets of the universe of PC diseases, the information from which is not generalizable to the universe of PCD patients. At this point in the history of PCD, there are not large enough databases of similar patients to provide a basis for valid randomized studies, with the exception of the surgical studies. Thus, a high index of suspicion of the early warning symptoms of PCD should lead to a rapid individual clinical assessment of patients selecting those with PCD. Medical, interventional, and/or surgical treatments should be chosen based on knowledge presented in this review. Recording the results in a national Registry on a continuing basis will provide the data that may help advance the management of PCD based on larger data bases of well documented patient information to guide the selection of future therapies for PCD treatments. It is also clear that the management of patients within the complex of diseases that comprise PCD should be performed in centers with expertise in the imaging, medical, interventional and surgical approaches to diseases of the PCD.

The Frequency of Substantial Salvageable Penumbra in Thrombectomy-ineligible Patients with Acute Stroke: Frequency of Nonperfusable Penumbra

Endovascular therapy (ET) has become the standard of care for selected patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). However, many LVO or medium vessel occlusion (MVO) patients are ineligible for ET, including some who harbor salvageable tissues. To develop complementary therapies for these patients, it is important to delineate their prevalence, clinical features, and outcomes.