Sookyung Ryoo

High-Resolution Magnetic Resonance Wall Imaging Findings of Moyamoya Disease

Background and Purpose— Diagnosis of Moyamoya disease (MMD) is based on the characteristic angiographic findings. However, differentiating MMD from intracranial atherosclerotic disease (ICAD) is difficult. We compared vessel wall imaging findings on high-resolution magnetic resonance imaging between MMD and ICAD. Methods— High-resolution magnetic resonance imaging was performed on 32 patients with angiographically proven MMD and 16 patients with acute infarcts because of ICAD. Bilateral internal carotid arteries and steno-occlusive middle cerebral artery were analyzed for wall enhancement and remodeling. Results— Enhancement patterns and distribution were different. Most patients with MMD (90.6%) showed concentric enhancement on distal internal carotid arteries and middle cerebral arteries, whereas focal eccentric enhancement was observed on the symptomatic segment in ICAD. MMD was characterized by middle cerebral artery shrinkage; the remodeling index and wall area were lower in MMD than in ICAD (remodeling index, 0.19±0.11 versus 1.00±0.43; wall area, 0.32±0.22 versus 6.00±2.72; P<0.001). Conclusions— MMD was characterized by concentric enhancement on bilateral distal internal carotid arteries and shrinkage of middle cerebral artery, regardless of symptoms.

A novel magnetic resonance imaging approach to collateral flow imaging in ischemic stroke

Dedicated magnetic resonance (MR) imaging (MRI) sequences for evaluation of collaterals can be generated using MR perfusion (MRP) source data. We compared a novel collateral flow imaging technique with digital subtraction angiography (DSA) for determining collateral circulation in acute stroke and evaluated the ability of MR‐based collateral flow maps to predict outcomes after recanalization therapy.

Adult Moyamoya Disease: A Burden of Intracranial Stenosis in East Asians?

Background Both Moyamoya disease (MMD) and intracranial atherosclerotic stenosis (ICAS) are more prevalent in Asians than in Westerners. We hypothesized that a substantial proportion of patients with adult-onset MMD were misclassified as having ICAS, which may in part explain the high prevalence of intracranial atherosclerotic stroke in Asians. Method We analyzed 352 consecutive patients with ischemic events within the MCA distribution and relevant intracranial arterial stenosis, but no demonstrable carotid or cardiac embolism sources. Conventional angiography was performed in 249 (70.7%) patients, and the remains underwent MRA. The occurrence of the c.14429G>A (p.Arg4810Lys) variant in ring finger protein 213 (RNF213) was analyzed. This gene was recently identified as a susceptibility gene for MMD in East Asians. Results The p.Arg4810Lys variant was observed in half of patients with intracranial stenosis (176 of 352, 50.0%), in no healthy control subjects (n = 51), and in 3.2% of stroke control subjects (4 of 124 patients with other etiologies). The presence of basal collaterals, bilateral involvement on angiography, and absence of diabetes were independently associated with the presence of the RNF213 variant. Among 131 patients who met all three diagnostic criteria and were diagnosed with MMD, three-fourths (75.6%) had this variant. However, a significant proportion of patients who met two criteria (57.7%), one criterion (28.6%), or no criteria (20.0%) also had this variant. Some of them developed typical angiographic findings of MMD on follow-up angiography. Conclusions Careful consideration of MMD is needed when diagnosing ICAS because differential therapeutic strategies are required for these diseases and due to the limitations of the current diagnostic criteria for MMD.

Differential Vascular Pathophysiologic Types of Intracranial Atherosclerotic Stroke A High-Resolution Wall Magnetic Resonance Imaging Study

Background and Purpose— Intracranial atherosclerotic stroke (ICAS) has various stroke mechanisms, including branch occlusive disease (BOD), subcortical infarcts caused by parent arterial disease occluding the perforator’s orifice, and non-BOD, infarcts beyond the subcortical area caused by artery-to-artery embolism. To test whether these 2 types of ICAS had different vascular pathophysiologies, we compared the high-resolution magnetic resonance imaging characteristics between BOD and non-BOD ICAS. Methods— Eighty patients with acute infarcts caused by ICAS of proximal middle cerebral artery or basilar artery without carotid/cardiac embolic sources or nonatherosclerotic causes were enrolled (36 BOD and 44 non-BOD patients). The steno-occlusive intracranial artery at the maximal stenosis was analyzed for vascular remodeling and wall enhancement. Results— BOD had distinct radiological features in terms of vascular morphology and enhancement. BOD showed a milder stenosis than non-BOD (P<0.001). Positive remodeling was more frequently observed in non-BOD than in BOD (P=0.005). Wall area index was also lower in BOD. Plaque enhancement was observed in all but one non-BOD patient and in one fourth of BOD patients (P=0.003). Although both types showed an eccentric enhancement, this enhancement was more frequently distributed in the BOD group on the side where the perforators arose. As the number of asymptomatic intracranial stenosis increased, the degree of stenosis (rho=0.513, P=0.003) increased in the BOD group, whereas enhanced plaque area (rho=0.343, P=0.030) increased in the non-BOD group. Conclusions— Our data indicate that BOD is a common and unique form of ICAS, distinct from non-BOD. These 2 types of ICAS have different vascular pathophysiologies in terms of vascular remodeling and plaque characteristics.

Differential Risk Factors for Lacunar Stroke Depending on the MRI (White and Red) Subtypes of Microangiopathy

Background Leukoaraiosis and cerebral microbleeds (CMB), which represent cerebral microangiopathy, commonly coexist in patients with acute lacunar stroke. Since they may have different impacts on stroke prognosis and treatment, it is important to know the factors associated with leukoaraiosis-predominant vs. CMB-predominant microangiopathies. Methods We prospectively recruited 226 patients with acute lacunar infarction and divided them into four groups according to the Fazekas’ score and the presence of CMB: mild, red (predominant CMB), white (predominant leukoaraiosis) and severe microangiopathy groups. For comparison, we also evaluated 50 patients with intracerebral hemorrhage (ICH). We evaluated the clinical and laboratory findings of microangiopathy subtypes in patients with acute lacunar stroke and then compared them with those of primary ICH. Results The risk factor profile was different among the groups. Patients with acute lacunar infarct but mild microangiopathy were younger, predominantly male, less hypertensive, and more frequently had smoking and heavy alcohol habits than other groups. The risk factor profile of red microangiopathy was similar to that of ICH but differed from that of white microangiopathy. The subjects in the white microangiopathy group were older and more frequently had diabetes than those in the red microangiopathy or ICH group. After adjustments for other factors, age [odds ratio (OR) 1.13; 95% confidence interval (CI) 1.08–1.18; p<0.001] and diabetes (OR 2.28; 95% CI 1.02–5.13; p = 0.045) were independently associated with white microangiopathy, and age (OR 1.05; 95% CI 1.01–1.08; p = 0.010) was independent predictor for red microangiopathy compared to mild microangiopathy. Conclusion Patients with acute lacunar infarction have a different risk factor profile depending on microangiopathic findings. Our results indicate that diabetes may be an one of determinants of white (leukoaraiosis-predominant) microangiopathy, whereas smoking and alcohol habits in relatively young people may be a determinants of mild microangiopahic changes in patients with lacunar infarction.

Patent Foramen Ovale and Stroke-Current Status.

Patent foramen ovale (PFO) is growing in clinical interest because of a renewed focus on embolic stroke of undetermined source (ESUS), the PFO attributable fraction (the 10-point Risk of Paradoxical Embolism score), technical advances in PFO diagnosis, and the emergence of endovascular device closure as a treatment option. However, recent randomized controlled trials of the management of patients with ESUS and PFO failed to demonstrate the superiority of closure over medical treatment. The mechanisms of stroke other than paradoxical embolism may be important in patients with ESUS and PFO. This paper reviews the current understanding of the pathophysiology of stroke and therapeutic options in patients with PFO and ESUS.

Eligibility and Preference of New Oral Anticoagulants in Patients With Atrial Fibrillation Comparison Between Patients With Versus Without Stroke

Background and Purpose— Recent randomized clinical trials (RCTs) have evaluated the benefit of new oral anticoagulants in reducing the risk of vascular events and bleeding complications in patients with atrial fibrillation (AF). However, abundant and strict enrollment criteria may limit the validity and applicability of results of RCTs to clinical practice. We estimated the eligibility for participation in RCTs of an unselected group of patients with AF. In addition, we compared features favoring new oral anticoagulant use between patients with versus without stroke. Randomized Evaluation of Long-Term Anticoagulation Therapy Methods— We applied enrollment criteria of 4 RCTs (RE-LY, ROCKET-AF, ARISTOTLE, and ENGAGE-AF-TIMI 48) to 695 patients with AF taking warfarin, prospectively and consecutively collected at a university medical center; 500 patients with and 195 patients without stroke. Time in therapeutic range and bleeding risk scheme (anticoagulation and risk factors in atrial fibrillation) were also measured. Results— The proportions of patients fulfilling the trial enrollment criteria varied, ranging from 39% to 72.8%, depending on the differences in indications/contraindications among studies and presence/absence of stroke. The main reasons for ineligibility for RCTs were hemorrhagic risk (anticoagulation and risk factors in atrial fibrillation [ATRIA] score) (10.8%–40.5%) and planned cardioversion (5.1%–7.7%) for nonstroke patients, and a low creatinine clearance (5.6%–9.2%) and higher risk of bleeding (15.2%–20.8%) for patients with stroke. When compared with nonstroke patients, patients with stroke showed a lower time in therapeutic range (54.4±42.8% versus 65.4±34.9%, especially with severe disability) and a high hemorrhagic risk (ATRIA score) (3.06±2.30 versus 2.18±2.16) (P<0.05 in both cases). Conclusions— Patients enrolled in RCTs are partly representative of patients with AF in clinical practice. When time in therapeutic range and bleeding tendency with warfarin use were considered, the use of new oral anticoagulants was preferred in patients with stroke than in nonstroke patients, but they were more likely to be excluded in RCTs.

Predicting Collateral Status With Magnetic Resonance Perfusion Parameters: Probabilistic Approach With a Tmax-Derived Prediction Model.

Background and Purpose— Good collateral flow is an important predictor for favorable responses to recanalization therapy and successful outcomes after acute ischemic stroke. Magnetic resonance perfusion–weighted imaging (MRP) is widely used in patients with stroke. However, it is unclear whether the perfusion parameters and thresholds would predict collateral status. The present study evaluated the relationship between hypoperfusion severity and collateral status to develop a predictive model for good collaterals using MRP parameters. Methods— Patients who were eligible for recanalization therapy that underwent both serial diffusion-weighted imaging and serial MRP were enrolled into the study. A collateral flow map derived from MRP source data was generated through automatic postprocessing. Hypoperfusion severity, presented as proportions of every 2-s Tmax strata to the entire hypoperfusion volume (Tmax≥2 s), was compared between patients with good and poor collaterals. Prediction models for good collaterals were developed with each Tmax strata proportion and cerebral blood volumes. Results— Among 66 patients, 53 showed good collaterals based on MRP-based collateral grading. Although no difference was noted in delays within 16 s, more severe Tmax delays (Tmax16–18 s, Tmax18–22 s, Tmax22–24 s, and Tmax>24 s) were associated with poor collaterals. The probability equation model using Tmax strata proportion demonstrated high predictive power in a receiver operating characteristic analysis (area under the curve=0.9303; 95% confidence interval, 0.8682–0.9924). The probability score was negatively correlated with the volume of infarct growth (P=0.030). Conclusions— Collateral status is associated with more severe Tmax delays than previously defined. The present Tmax severity–weighted model can determine good collaterals and subsequent infarct growth.

Dual Therapy with Cidofovir and Mirtazapine for Progressive Multifocal Leukoencephalopathy in a Sarcoidosis Patient

Background: Progressive multifocal leukoencephalopathy (PML) is a demyelinating central nervous system disease caused by JC virus (JCV) reactivation in immunocompromised patients. The disease course of PML is often progressive, fatal and at present, there are few reports on successful treatment outcomes. Case Report: A 45-year-old man with systemic sarcoidosis presented with rapidly progressive dementia and right hemiparesis. The patient was diagnosed with PML as confirmed via brain biopsy and JCV PCR. With a combination treatment of cidofovir and mirtazapine, there was significant improvement of neurological symptoms without measurable functional deficit. Conclusion: This case suggests that dual therapy with cidofovir and mirtazapine might be an effective treatment option in PML patients with sarcoidosis.

Sulcal Effacement on Fluid Attenuation Inversion Recovery Magnetic Resonance Imaging in Hyperacute Stroke Association With Collateral Flow and Clinical Outcomes

Background and Purpose— The clinical significance of sulcal effacement has been widely investigated in CT studies, but the results are controversial. In this study, we evaluated the presence of perisylvian sulcal effacement (PSE) on fluid attenuation inversion recovery MRI and hypothesized that PSE may be related to collateral flow status together with hyperintense vessels on fluid attenuation inversion recovery in hyperacute stroke. In addition, we investigated whether an association between PSE and clinical outcome could be found in these patients. Methods— Consecutive patients with acute middle cerebral artery infarcts within 6 hours of symptom onset were included. All patients had internal carotid artery or middle cerebral artery occlusion and underwent MRI including FLAIR. The presence of PSE and hyperintense vessels on fluid attenuation inversion recovery and the collateral status and occurrence of early recanalization (ER) on conventional angiography were evaluated. Results— Of 139 patients, 79 (56.8%) had PSE. Multivariate testing revealed PSE was independently associated with collateral status. The association between hyperintense vessels and collaterals was different depending on PSE. Compared to PSE-positive and ER-negative patients, PSE-negative and ER-negative patients (odds ratio, 4.11; 95% confidence interval, 1.12–15.17) and PSE-negative and ER-positive patients (odds ratio, 34.62; 95% confidence interval, 5.75–208.60), but not PSE-positive and ER-positive patients, were more likely to experience favorable clinical outcomes (modified Rankin Scale score ⩽2 at 3 months). Conclusions— PSE is independently associated with collateral status in patients with acute middle cerebral artery stroke. Moreover, PSE in conjunction with recanalization status can predict clinical outcomes in these patients.