New Directions in Infection-Associated Ischemic Stroke

The relationship between infections and stroke has not been fully characterized, probably delaying the development of specific treatments. This narrative review addresses mechanisms of stroke linked to infections, including hypercoagulability, endothelial dysfunction, vasculitis, and impaired thrombolysis. SARS-CoV-2, the virus that causes COVID-19, may promote the development of stroke, which may represent its most severe neurological complication. The development of specific therapies for infection-associated stroke remains a profound challenge. Perhaps the most important remaining issue is the distinction between infections that trigger a stroke versus infections that are truly incidental. This distinction likely requires the establishment of appropriate biomarkers, candidates of which are elevated levels of fibrin Ddimer and anticardiolipin/antiphospholipid antibodies. These candidate biomarkers might have potential use in identifying pathogenic infections preceding stroke, which is a precursor to establishing specific therapies for this syndrome.

A Multimodal Ensemble Deep Learning Model for Functional Outcome Prognosis of Stroke Patients / 대한뇌졸중학회지

Background@#and Purpose The accurate prediction of functional outcomes in patients with acute ischemic stroke (AIS) is crucial for informed clinical decision-making and optimal resource utilization. As such, this study aimed to construct an ensemble deep learning model that integrates multimodal imaging and clinical data to predict the 90-day functional outcomes after AIS. @*Methods@#We used data from the Korean Stroke Neuroimaging Initiative database, a prospective multicenter stroke registry to construct an ensemble model integrated individual 3D convolutional neural networks for diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR), along with a deep neural network for clinical data, to predict 90-day functional independence after AIS using a modified Rankin Scale (mRS) of 3–6. To evaluate the performance of the ensemble model, we compared the area under the curve (AUC) of the proposed method with that of individual models trained on each modality to identify patients with AIS with an mRS score of 3–6. @*Results@#Of the 2,606 patients with AIS, 993 (38.1%) achieved an mRS score of 3–6 at 90 days post-stroke. Our model achieved AUC values of 0.830 (standard cross-validation [CV]) and 0.779 (time-based CV), which significantly outperformed the other models relying on single modalities: b-value of 1,000 s/mm2 (P<0.001), apparent diffusion coefficient map (P<0.001), FLAIR (P<0.001), and clinical data (P=0.004). @*Conclusion@#The integration of multimodal imaging and clinical data resulted in superior prediction of the 90-day functional outcomes in AIS patients compared to the use of a single data modality.

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.

Moderate-Intensity Rosuvastatin Plus Ezetimibe Versus High-Intensity Rosuvastatin for Target Low-Density Lipoprotein Cholesterol Goal Achievement in Patients With Recent Ischemic Stroke: A Randomized Controlled Trial / 대한뇌졸중학회지

Background@#and Purpose Moderate-intensity statin plus ezetimibe versus high-intensity statin alone may provide a greater low-density lipoprotein cholesterol (LDL-C) reduction in patients with recent ischemic stroke. @*Methods@#This randomized, open-label, controlled trial assigned patients with recent ischemic stroke <90 days to rosuvastatin/ezetimibe 10/10 mg once daily (ROS10/EZT10) or to rosuvastatin 20 mg once daily (ROS20). The primary endpoint was LDL-C reduction ≥50% from baseline at 90 days. Key secondary endpoints were LDL-C <70 mg/dL and multiple lipid goal achievement, and composite of major vascular events. @*Results@#Of 584 randomized, 530 were included in the modified intention-to-treat analysis. The baseline LDL-C level was 130.2±34.7 mg/dL in the ROS10/EZT10 group and 131.0±33.9 mg/dL in the ROS20 group. The primary endpoint was achieved in 198 patients (72.5%) in the ROS10/EZT10 group and 148 (57.6%) in the ROS20 group (odds ratio [95% confidence interval], 1.944 [1.352–2.795]; P= 0.0003). LDL-C level <70 mg/dL was achieved in 80.2% and 65.4% in the ROS10/EZT10 and ROS20 groups (P=0.0001). Multiple lipid goal achievement rate was 71.1% and 53.7% in the ROS10/EZT10 and ROS20 groups (P<0.0001). Major vascular events occurred in 1 patient in the ROS10/EZT10 group and 9 in the ROS20 group (P=0.0091). The adverse event rates did not differ between the two groups. @*Conclusion@#Moderate-intensity rosuvastatin plus ezetimibe was superior to high-intensity rosuvastatin alone for intensive LDL-C reduction in patients with recent ischemic stroke. With the combination therapy, more than 70% of patients achieved LDL-C reduction ≥50% and 80% had an LDL-C <70 mg/dL at 90 days.

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.

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.

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.

Changes in High-Density Lipoprotein Cholesterol and Risks of Cardiovascular Events: A Post Hoc Analysis from the PICASSO Trial / 대한뇌졸중학회지

Background@#and purpose Whether pharmacologically altered high-density lipoprotein cholesterol (HDL-C) affects the risk of cardiovascular events is unknown. Recently, we have reported the Prevention of Cardiovascular Events in Asian Patients with Ischaemic Stroke at High Risk of Cerebral Haemorrhage (PICASSO) trial that demonstrated the non-inferiority of cilostazol to aspirin and superiority of probucol to non-probucol for cardiovascular prevention in ischemic stroke patients (clinicaltrials.gov: NCT01013532). We aimed to determine whether on-treatment HDL-C changes by cilostazol and probucol influence the treatment effect of each study medication during the PICASSO study. @*Methods@#Of the 1,534 randomized patients, 1,373 (89.5%) with baseline cholesterol parameters were analyzed. Efficacy endpoint was the composite of stroke, myocardial infarction, and cardiovascular death. Cox proportional hazards regression analysis examined an interaction between the treatment effect and changes in HDL-C levels from randomization to 1 month for each study arm. @*Results@#One-month post-randomization mean HDL-C level was significantly higher in the cilostazol group than in the aspirin group (1.08 mmol/L vs. 1.00 mmol/L, P<0.001). The mean HDL-C level was significantly lower in the probucol group than in the non-probucol group (0.86 mmol/L vs. 1.22 mmol/L, P<0.001). These trends persisted throughout the study. In both study arms, no significant interaction was observed between HDL-C changes and the assigned treatment regarding the risk of the efficacy endpoint. @*Conclusions@#Despite significant HDL-C changes, the effects of cilostazol and probucol treatment on the risk of cardiovascular events were insignificant. Pharmacologically altered HDL-C levels may not be reliable prognostic markers for cardiovascular risk.

Hyperintense Acute Reperfusion Marker on FLAIR in Patient with Possible Contrast-Induced Encephalopathy Following Cerebral Angiography

Contrast-induced encephalopathy (CIE) is a rare complication of angiography and endovascular intervention following administration of iodinated intravenous contrast agents. Neuroimaging findings of CIE usually show cerebral edema, leptomeningeal enhancement, and parenchymal signal abnormality on fluid-attenuated inverse recovery (FLAIR). Hyperintense acute reperfusion marker (HARM) generally implies an enhancement of the subarachnoid cerebrospinal fluid space on brain FLAIR imaging in cases of acute ischemic stroke or hyperperfusion syndrome. We report a case of possible CIE following cerebral angiography, accompanied by HARM sign.

Long-Term Outcomes of Real-World Korean Patients with Atrial-Fibrillation-Related Stroke and Severely Decreased Ejection Fraction

BACKGROUND AND PURPOSE: The clinical implications of echocardiography findings for long-term outcomes in atrial fibrillation (AF)-related stroke patients are unknown. METHODS: This was a substudy of the Korean ATrial fibrillaTion EvaluatioN regisTry in Ischemic strOke patieNts (K-ATTENTION), which is a multicenter-based cohort comprising prospective stroke registries from 11 tertiary centers. Stroke survivors who underwent two-dimensional transthoracic echocardiography during hospitalization were enrolled. Echocardiography markers included the left-ventricle (LV) ejection fraction (LVEF), the left atrium diameter, and the ratio of the peak transmitral filling velocity to the mean mitral annular velocity during early diastole (E/e′ ratio). LVEF was categorized into normal (≥55%), mildly decreased (>40% and <55%), and severely decreased (≤40%). The E/e′ ratio associated with the LV filling pressure was categorized into normal (<8), borderline (≥8 and <15), and elevated (≥15). Kaplan-Meier and Cox regression analyses were performed for recurrent stroke, major adverse cardiac events, and all-cause death. RESULTS: This study finally included 1,947 patients. Over a median follow-up of 1.65 years (interquartile range, 0.42–2.87 years), the rates of recurrent stroke, major adverse cardiac events, and all-cause death were 35.1, 10.8, and 69.6 cases per 1,000 person-years, respectively. Multivariable analyses demonstrated that severely decreased LVEF was associated with a higher risks of major adverse cardiac events [hazard ratio (HR), 3.91; 95% confidence interval (CI), 1.58–9.69] and all-cause death (HR, 1.95; 95% CI, 1.23–3.10). The multivariable fractional polynomial plot indicated that recurrent stroke might be associated with a lower LVEF. CONCLUSIONS: Severe LV systolic dysfunction could be a determinant of long-term outcomes in AF-related stroke.

Departmant of Neurology Sırnak State Hospital, Şırnak, Turkey

@#Isolated middle cerebral artery (MCA) dissection with atherosclerosis is a rare entity, and its clinical progression is not well known. We recently came across a case of isolated MCA dissection with atherosclerosis. A 62-year-old man presented to the emergency department with right-sided weakness and mild aphasia. Diffusion-weighted imaging (DWI) showed a multifocal infarction in the left MCA region, and perfusion Magnetic resonance imaging (MRI) detected a moderate time delay in the left MCA region. High-resolution MRI and transfemoral cerebral angiography revealed that the atherosclerotic plaque was accompanied by the dissecting intimal flap. Despite 40 days of antiplatelet therapy, the ischemic stroke recurred and the dissection did not heal. After stenting, the MCA and intracranial circulation revealed a widened lumen and improved flow across the dissection, and no embolic sequelae in the distal intracranial circulation. This case suggest that in MCA dissection with atherosclerosis, early stage intracranial stenting may be a better therapeutic strategy than medical treatment, to prevent recurrent cerebral infarction

Rotatory Vertebral Artery Syndrome in Foramen Magnum Stenosis / 대한평형의학회지

Rotatory vertebral artery syndrome (RVAS) is characterized by recurrent attacks of vertigo, nystagmus, and syncope induced by compression of the vertebral artery during head rotation. A 60-year-old man with atlas vertebrae fracture presented recurrent attacks of positional vertigo. Left-beat, upbeat and count clock-wise torsional nystagmus occurred after lying down and bilateral head roll (HR) showing no latency or fatigue. Magnetic resonance imaging revealed foramen magnum stenosis (FMS) and dominancy of right vertebral artery (VA). The flow of the right VA on transcranial Doppler decreased significantly during left HR. The slower the velocity was, the more the nystagmus was aggravated. RVAS can be evoked by FMS causing compression of the VA. And the nystagmus might be aggravated according to the blood flow insufficiency.

Hypointensity on Susceptibility-Weighted Images Prior to Signal Change on Diffusion-Weighted Images in a Hyperacute Ischemic Infarction: a Case Study

Susceptibility-weighted imaging (SWI) is well known for detecting the presence of hemorrhagic transformation, microbleeds and the susceptibility of vessel signs in acute ischemic stroke. But in some cases, it can provide the tissue perfusion state as well. We describe a case of a patient with hyperacute ischemic infarction that had a slightly hypodense, patchy lesion at the left thalamus on the initial SWI, with a left proximal posterior cerebral artery occlusion on a magnetic resonance (MR) angiography and delayed time-to-peak on an MR perfusion performed two hours after symptom onset. No obvious abnormal signals at any intensity were found on the initial diffusion-weighted imaging (DWI). On a follow-up MR image (MRI), an acute ischemic infarction was seen on DWI, which is the same location as the lesion on SWI. The hypointensity on the initial SWI reflects the susceptibility artifact caused by an increased deoxyhemoglobin in the affected tissue and vessels, which reflects the hypoperfusion state due to decreasing arterial flow. It precedes the signal change on DWI that reflects a cytotoxic edema. This case highlights that, in some hyperacute stages of ischemic stroke, hypointensity on an SWI may be a finding before the hyperintensity is seen on a DWI.

Reversible Cause of Rapidly Progressive Dementia as Presenting Symptom of Primary Hyperparathyroidism

Primary hyperparathyroidism (PHPT) is imbalance of calcium, phosphate, and bone metabolism attributed to an increased secretion of parathyroid hormone (PTH). Although PHPT is mainly associated with musculoskeletal and kidney dysfunction, variable symptoms can be presented in the elderly patients. A 75-year-old man presented with rapidly progressive dementia (RPD). Through etiological work-up of hypercalcemia and increased PTH, parathyroid adenoma was found. Subtotal parathyroidectomy resulted in recovery of cognitive impairment. Primary hyperparathyroidism should be considered in a differential diagnosis of RPD.

Ictal Eletroencephalographic Findings of Nonconvulsive Status Epilepticus Associated With Glufosinate Ammonium Poisoning

No abstract available.

Loneliness in Elderly Patients with Mild Cognitive Impairment: A Pilot Study

BACKGROUND AND PURPOSE: Loneliness is a significant concern among the elderly, particularly in societies with rapidly growing aging populations. While loneliness may influence neuropsychological function, the exact nature of the association between loneliness and neuropsychological function is poorly understood. METHODS: We evaluated 50 elderly patients with mild cognitive impairment (MCI) and 33 without cognitive dysfunction with respect to demographics, clinical characteristics, cognitive and functional performance, depression scale, and loneliness scale. The associations between loneliness and neuropsychological assessments were evaluated. RESULTS: Although loneliness was not associated with cognitive or functional performance, it was correlated with depression in elderly patients. For elderly patients with MCI, depressive symptoms were reported more frequently in individuals with a high degree of loneliness (p < 0.05). CONCLUSIONS: Neither cognitive performance nor functional performance is associated with loneliness; however, loneliness is associated with depressive symptoms in elderly patients with MCI.

Abnormal Head Impulse Test in a Unilateral Cerebellar Lesion

BACKGROUND: The findings of head impulse tests (HIT) are usually normal in cerebellar lesions. CASE REPORT: A 46-year-old male presented with progressive dizziness and imbalance of 3 weeks duration. The patient exhibited catch-up saccades during bedside horizontal HIT to either side, which was more evident during the rightward HIT. However, results of bithermal caloric tests and rotatory chair test were normal. MRI revealed a lesion in the inferior cerebellum near the flocculus. CONCLUSIONS: This case provides additional evidence that damage to the flocculus or its connections may impair the vestibulo-ocular reflex only during high-speed stimuli, especially when the stimuli are applied to the contralesional side. By observing accompanying cerebellar signs, the abnormal HIT findings caused by a cerebellar disorder can be distinguished from those produced by peripheral vestibular disorders.

Atypical Presentation of Cerebral Superficial Siderosis Mimicking Recurrent Sciatic Neuralgia

No abstract available.

Bilateral Mirror Movement in Hemiparkinsonism-hemiatrophy Syndrome

No abstract available.

Acute Ischemic Vestibulopathy without Hearing Loss

Acute isolated vestibulopathy could be caused by either viral inflammation or ischemia. However, diagnosing ischemic vestibulopathy is difficult due to the ambiguity of the causal relationship between ischemia and peripheral vestibulopathy. We present here a patient with acute ischemic vestibulopathy without hearing loss caused by internal auditory artery occlusion, indirectly proven by the finding of a simultaneously developed silent cerebellar infarction. The details of this case suggest that patients with acute isolated peripheral vestibulopathy should be carefully evaluated for underlying causes, including vascular risk factors.