A Case of Anterior Communicating Artery Aneurysm Impending Rupture Presenting with Isolated Painful Adduction Palsy Mimicking Ischemic Internuclear Ophthalmoplegia

Anterior communicating artery (ACoA) aneurysms may rarely lead to oculomotor nerve palsy. We present here interesting cases in which isolated unilateral adduction paresis mimicking internuclear ophthalmoplegia (INO) was one of the symptoms of suspicious impending ruptured aneurysm of the ACoA. Careful neurologic examination is crucial for early discrimination with INO and oculomotor palsy.

Update on the Epidemiology, Pathogenesis, and Biomarkers of Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic disorder of the cerebral small blood vessels. It is caused by mutations in the NOTCH3 gene on chromosome 19, and more than 280 distinct pathogenic mutations have been reported to date. CADASIL was once considered a very rare disease with an estimated prevalence of 1.3–4.1 per 100,000 adults. However, recent large-scale genomic studies have revealed a high prevalence of pathogenic NOTCH3 variants among the general population, with the highest risk being among Asians. The disease severity and age at onset vary significantly even among individuals who carry the same NOTCH3 mutations. It is still unclear whether a significant genotype–phenotype correlation is present in CADASIL. The accumulation of granular osmiophilic material in the vasculature is a characteristic feature of CADASIL. However, the exact pathogenesis of CADASIL remains largely unclear despite various laboratory and clinical observations being made. Major hypotheses proposed so far have included aberrant NOTCH3 signaling, toxic aggregation, and abnormal matrisomes. Several characteristic features have been observed in the brain magnetic resonance images of patients with CADASIL, including subcortical lacunar lesions and white matter hyperintensities in the anterior temporal lobe or external capsule, which were useful in differentiating CADASIL from sporadic stroke in patients. The number of lacunes and the degree of brain atrophy were useful in predicting the clinical outcomes of patients with CADASIL. Several promising blood biomarkers have also recently been discovered for CADASIL, which require further research for validation.

Stroke-Specific Predictors of Major Bleeding in Anticoagulated Patients With Stroke and Atrial Fibrillation: A Nationwide Multicenter Registry-Based Study

Background@#and Purpose The congestive heart failure, hypertension, age, diabetes, previous stroke/transient ischemic attack (CHA2DS2-VASc) and hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol (HAS-BLED) scores have been validated in estimating the risks of ischemic stroke and major bleeding, respectively, in patients with atrial fibrillation (AF). This study investigated stroke-specific predictors of major bleeding in patients with stroke and AF who were taking oral anticoagulants (OACs). @*Methods@#Subjects were selected from patients enrolled in the Korean ATrial fibrillaTion EvaluatioN regisTry in Ischemic strOke patieNts (K-ATTENTION) nationwide multicenter registry between 2013 and 2015. Patients were excluded if they were not taking OACs, had no brain imaging data, or had intracranial bleeding directly related to the index stroke. Major bleeding was defined according to International Society of Thrombosis and Haemostasis criteria. Cox regression analyses were performed to assess the associations between clinical variables and major bleeding and Kaplan-Meier estimates were performed to analyze event-free survival. @*Results@#Of a total of 3,213 patients, 1,414 subjects (mean age of 72.6 years, 52.5% males) were enrolled in this study. Major bleeding was reported in 34 patients during the median follow-up period of 1.73 years. Multivariable analysis demonstrated that initial National Institutes of Health Stroke Scale scores (hazard ratio [HR] 1.07, p=0.006), hypertension (HR 3.18, p=0.030), persistent AF type (HR 2.51, p=0.016), and initial hemoglobin level (HR 0.74, p=0.001) were independently associated with major bleeding risk. Except for hypertension, these associations remained significant after adjusting for the HAS-BLED score. Intracranial atherosclerosis presented a trend of association without statistical significance (HR 2.21, p=0.050). @*Conclusions@#This study found that major bleeding risk was independently associated with stroke-specific factors in anticoagulated patients with stroke and AF. This has the clinical implication that baseline characteristics of patients with stroke and AF should be considered in secondary prevention, which would bring the net clinical benefit of balancing recurrent stroke prevention with minimal bleeding complications.

Safety and Efficacy of Intravenous Thrombolysis in the 3- to 4.5-hour Window in Acute Ischemic Stroke Patients Who Have Both Diabetes Mellitus and History of Prior Stroke

Background@#For acute ischemic stroke (AIS) patients with history of prior stroke (PS) and diabetes mellitus (DM), intravenous recombinant tissue plasminogen activator (IV-tPA) therapy in the 3- to 4.5-hour window is off-label in Korea. This study aimed to assess the safety and efficacy of IV-tPA in these patients. @*Methods@#Using data from a prospective multicenter stroke registry between January 2009 and March 2021, we identified AIS patients who received IV-tPA in the 3- to 4.5-hour window, and compared the outcomes of symptomatic intracranial hemorrhage (SICH), 3-month mortality, 3-month modified Rankin Scale (mRS) score 0-1 and 3-month mRS distribution between patients with both PS and DM (PS/DM, n=56) versus those with neither PS nor DM, or with only one (non-PS/DM, n=927). @*Results@#The PS/DM group versus the non-PS/DM group was more likely to have a prior disability, hypertension, hyperlipidemia, coronary heart disease and less likely to have atrial fibrillation. The PS/DM and the non-PS/DM groups had comparable rates of SICH (0% vs. 1.7%; p>0.999) and 3-month mortality (10.7% vs. 10.2%; p=0.9112). The rate of 3-month mRS 0-1 was non-significantly lower in the PS/DM group than in the non-PS/DM group (30.4% vs. 40.7%; adjusted odds ratio [95% confidence interval], 0.81 [0.41-1.59]). @*Conclusions@#In the 3- to 4.5-hour window, AIS patients with PS/DM, as compared to those with non-PS/DM, might benefit less from IV-tPA. However, given the similar risks of SICH and mortality, IV-tPA in the late time window could be considered in patients with both PS and DM.

Impact of Brain MRI Markers on Major and Mild Vascular Cognitive Impairment in CADASIL

Background@#Cognitive impairment is the second most common clinical manifestation in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, understanding of cognitive impairment in CADASIL has been hampered by lack of consensus on diagnosis of vascular cognitive impairment (VCI). We used vascular impairment of cognition classification consensus study principles (VICCCS-1) and protocols (VICCCS-2) to assess the cognitive impairment in CADASIL. We also evaluated the impact of MRI markers on major and mild VCI in CADASIL. @*Methods@#We prospectively recruited 64 patients who underwent standardized brain MRI and detailed neuropsychological test. MRI analysis included number of lacunes, number of cerebral microbleeds (CMB), normalized volume of white-matter hyperintensities (nWMH), and brain parenchymal fraction (BPF). BPF has been used to measure brain atrophy. The patients were divided into three groups: those with normal cognition (CADASIL-NC, n=14), those with mild VCI (CADASIL-mild VCI, n=38), and those with major VCI (CADASIL-major VCI, n=11). @*Results@#The three groups differed according to age, with the major VCI group being older. The major VCI group had more lacunes, more CMB, more extensive white matter lesions and lower BPF than NC group. There were no significant differences between NC and mild VCI groups in BPF. BPF and age were the independent predictors of major VCI. There was a tendency that women were at higher risk for mild VCI, though it did not reach statistical significance. Women were older than men, but had lower number of lacunes in mild VCI. @*Conclusions@#These findings suggest that brain atrophy and age are the main predictors of major VCI in CADASIL.

Delayed Development of Symptomatic Arterial Stenosis after a Mechanical Thrombectomy for an Acute Embolic Occlusion of the Middle Cerebral Artery

Delayed stenosis of the treated artery following mechanical thrombectomy is known to occur in approximately 10% of the patients after the procedure. It is usually asymptomatic, and was frequently found within 1 year after the procedure. Here we report a 58-year-old stroke patient who suffered from recurrent transient ischemic attacks due to a delayed stenosis of the middle cerebral artery 2 years after the mechanical thrombectomy for an abrupt embolic occlusion of the vessel.

Reversal of Diffusion-Weighted Imaging Hyperintensities of the Pons after Endovascular Reperfusion for Proximal Extracranial Vertebral Artery Occlusion

Diffusion-weighted imaging (DWI) hyperintensities corresponding to ischemic areas have been regarded as an ischemic core. However, several studies have demonstrated the reversibility of DWI hyperintense signals in hyperacute stroke patients. We experienced the DWI reversibility of posterior circulation ischemia after revascularization of the proximal extracranial vertebral artery. The perfusion of the posterior circulation might be significantly reduced due to bilateral vertebral art ery occlusion. Considering this case, early improvement of the perfusion of the ischemic area might key role of DWI reversibility.

2022 Update of the Korean Clinical Practice Guidelines for Stroke: Antithrombotic Therapy for Patients with Acute Ischemic Stroke or Transient Ischemic Attack / 대한뇌졸중학회지

Antithrombotic therapy is a cornerstone of acute ischemic stroke (AIS) management and secondary stroke prevention. Since the first version of the Korean Clinical Practice Guideline (CPG) for stroke was issued in 2009, significant progress has been made in antithrombotic therapy for patients with AIS, including dual antiplatelet therapy in acute minor ischemic stroke or high-risk transient ischemic stroke and early oral anticoagulation in AIS with atrial fibrillation. The evidence is widely accepted by stroke experts and has changed clinical practice. Accordingly, the CPG Committee of the Korean Stroke Society (KSS) decided to update the Korean Stroke CPG for antithrombotic therapy for AIS. The writing members of the CPG committee of the KSS reviewed recent evidence, including clinical trials and relevant literature, and revised recommendations. A total of 35 experts were invited from the KSS to reach a consensus on the revised recommendations. The current guideline update aims to assist healthcare providers in making well-informed decisions and improving the quality of acute stroke care. However, the ultimate treatment decision should be made using a holistic approach, considering the specific medical conditions of individual patients.

Risk of Subsequent Events in Patients With Minor Ischemic Stroke or HighRisk Transient Ischemic Attack

This study aimed to present the prognosis after minor acute ischemic stroke (AIS) or transient ischemic attack (TIA), using a definition of subsequent stroke in accordance with recent clinical trials. In total, 9,506 patients with minor AIS (National Institutes of Health Stroke Scale ≤ 5) or high-risk TIA (acute lesions or ≥ 50% cerebral artery steno-occlusion) admitted between November 2010 and October 2013 were included. The primary outcome was the composite of stroke (progression of initial event or a subsequent event) and all-cause mortality. The cumulative incidence of stroke or death was 11.2% at 1 month, 13.3% at 3 months and 16.7% at 1 year. Incidence rate of stroke or death in the first month was 12.5 per 100 person-months: highest in patients with large artery atherosclerosis (17.0). The risk of subsequent events shortly after a minor AIS or high-risk TIA was substantial, particularly in patients with large artery atherosclerosis.

Unrecognized Ruptured Intracranial Aneurysm Presenting as Cerebral Vasospasm-Induced Ischemic Stroke: A Case Report / 신경중재치료의학

A 44-year-old woman presented with acute confusion, apparently due to a clinically silent subarachnoid hemorrhage followed by vasospasm, which in turn led to an ischemic stroke. During the initial evaluation, an acute ischemic stroke in the left middle cerebral artery territory was observed. Magnetic resonance imaging revealed a late subacute hemorrhage in the left basal cistern. Digital subtraction angiography indicated the presence of a small saccular aneurysm that had recently ruptured, as well as vasospasm in the left circle of Willis. Balloon angioplasty and balloon-assisted coil embolization were performed for the vasospasm and saccular aneurysm, respectively. This case demonstrates that clinically silent subarachnoid hemorrhages resulting in ipsilateral vasospasm and infarction can occur as complications of a ruptured aneurysm.

Initiation of Guideline-Matched Oral Anticoagulant in Atrial Fibrillation-Related Stroke / 대한뇌졸중학회지

Background@#and Purpose To evaluate the outcome events and bleeding complications of the European Society of Cardiology (ESC) guideline-matched oral anticoagulant therapy for patients with acute ischemic stroke and atrial fibrillation (AF). @*Methods@#Patients with acute ischemic stroke and AF from a nationwide multicenter registry (Korean ATrial fibrillaTion EvaluatioN regisTry in Ischemic strOke patieNts [K-ATTENTION]) between January 2013 and December 2015 were included in the study. Patients were divided into the ESC guideline-matched and the non-matched groups. The primary outcome was recurrence of any stroke during the 90-day follow-up period. Secondary outcomes were major adverse cerebrovascular and cardiovascular events, ischemic stroke, intracranial hemorrhage, acute coronary syndrome, allcause mortality, and major hemorrhage. Propensity score matching and logistic regression analyses were performed to assess the effect of the treatments administered. @*Results@#Among 2,321 eligible patients, 1,126 patients were 1:1 matched to the ESC guidelinematched and the non-matched groups. As compared with the non-matched group, the ESC guideline-matched group had a lower risk of any recurrent stroke (1.4% vs. 3.4%; odds ratio [OR], 0.41; 95% confidence interval [CI], 0.18 to 0.95). The risk of recurrent ischemic stroke was lower in the ESC guideline-matched group than in the non-matched group (0.9% vs. 2.7%; OR, 0.32; 95% CI, 0.11 to 0.88). There was no significant difference in the other secondary outcomes between the two groups. @*Conclusions@#ESC guideline-matched oral anticoagulant therapy was associated with reduced risks of any stroke and ischemic stroke as compared with the non-matched therapy.

Isolated Intraventricular Hemorrhage after Carotid Artery Stenting

Cerebral intraventricular hemorrhage (IVH) is an extremely rare complication of carotid artery stenting (CAS). Fully dilated terminal arteries of a chronic, severely stenosed proximal artery could be ruptured by impaired autoregulation of cerebral blood flow. Hyperperfusion syndrome can occur even if there is no blood pressure fluctuation during the CAS. We report a case of an isolated IVH that occurred hours after CAS.

Effect of Transport Time on the Use of Reperfusion Therapy for Patients with Acute Ischemic Stroke in Korea

Background@#We investigated the association between geographic proximity to hospitals and the administration rate of reperfusion therapy for acute ischemic stroke. @*Methods@#We identified patients with acute ischemic stroke who visited the hospital within 12 hours of symptom onset from a prospective nationwide multicenter stroke registry. Reperfusion therapy was classified as intravenous thrombolysis (IVT), endovascular therapy (EVT), or combined therapy. The association between the proportion of patients who were treated with reperfusion therapy and the ground transport time was evaluated using a spline regression analysis adjusted for patient-level characteristics. We also estimated the proportion of Korean population that lived within each 30-minute incremental service area from 67 stroke centers accredited by the Korean Stroke Society. @*Results@#Of 12,172 patients (mean age, 68 ± 13 years; men, 59.7%) who met the eligibility criteria, 96.5% lived within 90 minutes of ground transport time from the admitting hospital. The proportion of patients treated with IVT decreased significantly when stroke patients lived beyond 90 minutes of the transport time (P = 0.006). The proportion treated with EVT also showed a similar trend with the transport time. Based on the residential area, 98.4% of Korean population was accessible to 67 stroke centers within 90 minutes. @*Conclusion@#The use of reperfusion therapy for acute stroke decreased when patients lived beyond 90 minutes of the ground transport time from the hospital. More than 95% of the South Korean population was accessible to 67 stroke centers within 90 minutes of the ground transport time.

Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia: The Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia Study

Background@#and Purpose: Blood pressure (BP) control is strongly recommended, but BP control rate has not been well studied in patients with stroke. We evaluated the BP control rate with fimasartan-based antihypertensive therapy initiated in patients with recent cerebral ischemia. @*Methods@#This multicenter, prospective, single-arm trial involved 27 centers in South Korea. Key inclusion criteria were recent cerebral ischemia within 90 days and high BP [systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg]. BP lowering was initiated with fimasartan. BP management during the follow-up was at the discretion of the responsible investigators. The primary endpoint was the target BP goal achievement rate (<140/90 mm Hg) at 24 weeks. Key secondary endpoints included achieved BP and BP changes at each visit, and clinical events (ClinicalTrials.gov Identifier: NCT03231293). @*Results@#Of 1,035 patients enrolled, 1,026 were included in the safety analysis, and 951 in the efficacy analysis. Their mean age was 64.1 years, 33% were female, the median time interval from onset to enrollment was 10 days, and the baseline SBP and DBP were 162.3±16.0 and 92.2±12.4 mm Hg (mean±SD). During the study period, 55.5% of patients were maintained on fimasartan monotherapy, and 44.5% received antihypertensive therapies other than fimasartan monotherapy at at least one visit. The target BP goal achievement rate at 24-week was 67.3% (48.6% at 4-week and 61.4% at 12-week). The mean BP was 139.0/81.8±18.3/11.7, 133.8/79.2±16.4/11.0, and 132.8/78.5±15.6/10.9 mm Hg at 4-, 12-, and 24-week. The treatment-emergent adverse event rate was 5.4%, including one serious adverse event. @*Conclusions@#Fimasartan-based BP lowering achieved the target BP in two-thirds of patients at 24 weeks, and was generally well tolerated.

Unrecognized Ruptured Intracranial Aneurysm Presenting as Cerebral Vasospasm-Induced Ischemic Stroke: A Case Report / 신경중재치료의학

A 44-year-old woman presented with acute confusion, apparently due to a clinically silent subarachnoid hemorrhage followed by vasospasm, which in turn led to an ischemic stroke. During the initial evaluation, an acute ischemic stroke in the left middle cerebral artery territory was observed. Magnetic resonance imaging revealed a late subacute hemorrhage in the left basal cistern. Digital subtraction angiography indicated the presence of a small saccular aneurysm that had recently ruptured, as well as vasospasm in the left circle of Willis. Balloon angioplasty and balloon-assisted coil embolization were performed for the vasospasm and saccular aneurysm, respectively. This case demonstrates that clinically silent subarachnoid hemorrhages resulting in ipsilateral vasospasm and infarction can occur as complications of a ruptured aneurysm.

Isolated Intraventricular Hemorrhage after Carotid Artery Stenting

Cerebral intraventricular hemorrhage (IVH) is an extremely rare complication of carotid artery stenting (CAS). Fully dilated terminal arteries of a chronic, severely stenosed proximal artery could be ruptured by impaired autoregulation of cerebral blood flow. Hyperperfusion syndrome can occur even if there is no blood pressure fluctuation during the CAS. We report a case of an isolated IVH that occurred hours after CAS.

Effect of Transport Time on the Use of Reperfusion Therapy for Patients with Acute Ischemic Stroke in Korea

Background@#We investigated the association between geographic proximity to hospitals and the administration rate of reperfusion therapy for acute ischemic stroke. @*Methods@#We identified patients with acute ischemic stroke who visited the hospital within 12 hours of symptom onset from a prospective nationwide multicenter stroke registry. Reperfusion therapy was classified as intravenous thrombolysis (IVT), endovascular therapy (EVT), or combined therapy. The association between the proportion of patients who were treated with reperfusion therapy and the ground transport time was evaluated using a spline regression analysis adjusted for patient-level characteristics. We also estimated the proportion of Korean population that lived within each 30-minute incremental service area from 67 stroke centers accredited by the Korean Stroke Society. @*Results@#Of 12,172 patients (mean age, 68 ± 13 years; men, 59.7%) who met the eligibility criteria, 96.5% lived within 90 minutes of ground transport time from the admitting hospital. The proportion of patients treated with IVT decreased significantly when stroke patients lived beyond 90 minutes of the transport time (P = 0.006). The proportion treated with EVT also showed a similar trend with the transport time. Based on the residential area, 98.4% of Korean population was accessible to 67 stroke centers within 90 minutes. @*Conclusion@#The use of reperfusion therapy for acute stroke decreased when patients lived beyond 90 minutes of the ground transport time from the hospital. More than 95% of the South Korean population was accessible to 67 stroke centers within 90 minutes of the ground transport time.

Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia: The Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia Study

Background@#and Purpose: Blood pressure (BP) control is strongly recommended, but BP control rate has not been well studied in patients with stroke. We evaluated the BP control rate with fimasartan-based antihypertensive therapy initiated in patients with recent cerebral ischemia. @*Methods@#This multicenter, prospective, single-arm trial involved 27 centers in South Korea. Key inclusion criteria were recent cerebral ischemia within 90 days and high BP [systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg]. BP lowering was initiated with fimasartan. BP management during the follow-up was at the discretion of the responsible investigators. The primary endpoint was the target BP goal achievement rate (<140/90 mm Hg) at 24 weeks. Key secondary endpoints included achieved BP and BP changes at each visit, and clinical events (ClinicalTrials.gov Identifier: NCT03231293). @*Results@#Of 1,035 patients enrolled, 1,026 were included in the safety analysis, and 951 in the efficacy analysis. Their mean age was 64.1 years, 33% were female, the median time interval from onset to enrollment was 10 days, and the baseline SBP and DBP were 162.3±16.0 and 92.2±12.4 mm Hg (mean±SD). During the study period, 55.5% of patients were maintained on fimasartan monotherapy, and 44.5% received antihypertensive therapies other than fimasartan monotherapy at at least one visit. The target BP goal achievement rate at 24-week was 67.3% (48.6% at 4-week and 61.4% at 12-week). The mean BP was 139.0/81.8±18.3/11.7, 133.8/79.2±16.4/11.0, and 132.8/78.5±15.6/10.9 mm Hg at 4-, 12-, and 24-week. The treatment-emergent adverse event rate was 5.4%, including one serious adverse event. @*Conclusions@#Fimasartan-based BP lowering achieved the target BP in two-thirds of patients at 24 weeks, and was generally well tolerated.

Status Epilepticus as the Initial Manifestation of Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-Like Episodes Syndrome

Mitochondrial encephalomyopathy with lactic acid and stroke-like episodes (MELAS) is a multisystem mitochondrial disorder that is rarely observed in adulthood. We report a case of MELAS syndrome diagnosed in a 22-year-old man presented with status epilepticus (SE) without a preceding stroke-like episode. Genetic testing revealed a mutation of heteroplasmic m.3243A>G. MELAS should be suspected in patients with recurrent, uncontrolled SE with unexplained severe lactic acidosis.

Oculomotor Nerve Palsy that Developed after Endovascular Treatment in an Acute Stroke Patient with a Dissecting Occlusion of the Extracranial Internal Carotid Artery

Oculomotor nerve palsy is underrecognized clinical manifestation of extracranial internal carotid artery (ICA) dissection. Herein we report a case of complete oculomotor nerve palsy following endovascular revascularization, which developed in a patient with acute stroke due to extracranial ICA dissecting occlusion. We also discuss about the development mechanism of oculomotor nerve palsy, considering the vascular anatomy and the possibility of periprocedural complications during endovascular treatment.