Clinical and Genetic Characteristics Associated With Survival Outcome in Late-Onset Huntington's Disease in South Korea.

BACKGROUND AND PURPOSE: The onset of Huntington's disease (HD) usually occurs before the age of 50 years, and the median survival time from onset is 15 years. We investigated survival in patients with late-onset HD (LoHD) (age at onset ≥60 years) and the associations of the number of mutant CAG repeats and age at onset (AAO) with survival in patients with HD. METHODS: Patients with genetically confirmed HD at six referral centers in South Korea between 2000 and 2020 were analyzed retrospectively. Baseline demographic, clinical, and genetic characteristics and the survival status as at December 2020 were collected. RESULTS: Eighty-seven patients were included, comprising 26 with LoHD (AAO=68.77±5.91 years, mean±standard deviation; 40.54±1.53 mutant CAG repeats) and 61 with common-onset HD (CoHD) (AAO=44.12±8.61 years, 44.72±4.27 mutant CAG repeats). The ages at death were 77.78±7.46 and 53.72±10.86 years in patients with LoHD and CoHD, respectively (p<0.001). The estimated survival time was 15.21±2.49 years for all HD patients, and 10.74±1.95 and 16.15±2.82 years in patients with LoHD and CoHD, respectively. More mutant CAG repeats and higher AAO were associated with shorter survival (hazard ratio [HR]=1.05, 95% confidence interval [CI]=1.01-1.09, p=0.019; and HR=1.17, 95% CI=1.03-1.31, p=0.013; respectively) for all HD patients. The LoHD group showed no significant factors associated with survival after disease onset, whereas the number of mutant CAG repeats had a significant effect (HR=1.12, 95% CI=1.01-1.23, p=0.034) in the CoHD group. CONCLUSIONS: Survival after disease onset was shorter in patients with LoHD than in those with CoHD. More mutant CAG repeats and higher AAO were associated with shorter survival in patients with HD.

Hypointense signal lesion on susceptibility-weighted imaging as a potential indicator of vertebral artery dissection in medullary infarction.

Vertebral artery dissection (VAD) is often associated with medullary infarction; however, an underlying cause may be underestimated. This study aimed to assess the diagnostic potential of hypointense signal lesions along the arterial pathways using susceptibility-weighted imaging (SWI) as a feasible indicator of VAD in medullary infarction. A retrospective analysis was conducted using clinical data, brain magnetic resonance imaging, and angiography records of 79 patients diagnosed with medullary infarction between January 2014 and December 2021. Patients were categorized into an angiography-confirmed dissection group and a non-dissection group based on imaging findings. A new possible dissection group was identified using SWI, including cases with hypointense signals along the arteries without calcification or cardioembolism. We compared the clinical characteristics of the two groups before and after the addition of the hypointense signal as a marker of VAD. The angiography-confirmed dissection group included 12 patients (15%). Among patients lacking angiographic VAD evidence, 14 subjects displayed hypointense signals on SWI: nine patients along the vertebral artery and five subjects at the posterior inferior cerebellar artery without calcification or cardioembolism. The newly classified dissection group was younger, had a lower prevalence of diabetes mellitus and stroke history, and revealed increased headaches compared to the non-dissection group. Hypointense signal detection on SWI in medullary infarctions shows promise as a diagnostic indicator for VAD. Suspicion of VAD is needed when the hypointense signal on SWI is noted, and considering different treatment strategies with angiographic follow-up will be helpful.

Regiodivergent Ring-Expansion of Oxindoles to Quinolinones.

The development of divergent methods to expedite structure-activity relationship studies is crucial to streamline discovery processes. We developed a rare example of regiodivergent ring expansion to access two regioisomers from a common starting material. To enable this regiodivergence, we identified two distinct reaction conditions for transforming oxindoles into quinolinone isomers. The presented methods proved to be compatible with a variety of functional groups, which enabled the late-stage diversification of bioactive oxindoles as well as facilitated the synthesis of quinolinone drugs and their derivatives.

Quantitative and qualitative mutational impact of ionizing radiation on normal cells.

The comprehensive genomic impact of ionizing radiation (IR), a carcinogen, on healthy somatic cells remains unclear. Using large-scale whole-genome sequencing (WGS) of clones expanded from irradiated murine and human single cells, we revealed that IR induces a characteristic spectrum of short insertions or deletions (indels) and structural variations (SVs), including balanced inversions, translocations, composite SVs (deletion-insertion, deletion-inversion, and deletion-translocation composites), and complex genomic rearrangements (CGRs), including chromoplexy, chromothripsis, and SV by breakage-fusion-bridge cycles. Our findings suggest that 1 Gy IR exposure causes an average of 2.33 mutational events per Gb genome, comprising 2.15 indels, 0.17 SVs, and 0.01 CGRs, despite a high level of inter-cellular stochasticity. The mutational burden was dependent on total irradiation dose, regardless of dose rate or cell type. The findings were further validated in IR-induced secondary cancers and single cells without clonalization. Overall, our study highlights a comprehensive and clear picture of IR effects on normal mammalian genomes.

Acute ischemic stroke in Tsutsugamushi: understanding the underlying mechanisms and risk factors.

BACKGROUND: Tsutsugamushi (scrub typhus) is an acute infectious febrile disease common in the Asia-Pacific region. Common symptoms of tsutsugamushi include lymphadenopathy, fever, and myalgia, and it rarely causes acute ischemic stroke (AIS). However, we hypothesized that tsutsugamushi infection could trigger AIS. METHOD: We retrospectively examined patients diagnosed with AIS within 2 weeks of tsutsugamushi diagnosis at three hospitals over a 15-year period. We categorized patients who developed AIS while being treated for tsutsugamushi as the case group and those (of similar age and sex) who did not develop AIS as the control group. The case and control groups consisted of 22 and 66 participants, respectively. When a scattered pattern was observed or lesions were found in two or more vascular territories on diffusion-weighted imaging, the pattern was defined as embolic. Other patterns were defined as nonembolic. RESULTS: Among the 19 patients, excluding three with transient ischemic stroke, 15 (78.9%) showed an embolic pattern. Although fever was common in the control group, it was less common in the case group. A higher D-dimer level at the time of hospitalization was associated with the development of AIS in patients with tsutsugamushi. CONCLUSIONS: AIS in patients with tsutsugamushi showed an embolic rather than a non-embolic pattern on brain magnetic resonance imaging. It was more likely to occur in patients with risk factors for stroke. Tsutsugamushi patients with AIS were likely to have no fever or high D-dimer levels. We hypothesized that D-dimers play an important role in the pathophysiology, where tsutsugamushi infection increases the likelihood of AIS.

Headaches during pregnancy and the risk of subsequent stroke.

BACKGROUND: Primary headache disorder is a known risk factor for stroke in women and usually improves during the first trimester of pregnancy. However, despite this, some women develop headaches during pregnancy (G-HA), and the effect of this headache on subsequent stroke is unknown. In this study, we evaluated the association between G-HA and stroke after delivery in women. METHODS: Based on the Korean National Health Insurance Service database, we included women hospitalized for delivery between 2012 and 2013. G-HA was defined as a headache diagnosed during pregnancy. Primary outcome was any stroke that occurred during the observational periods from delivery to December 31, 2020. All diseases were identified based on data registered in the database using the International Classification of Disease-10th Revision-Clinical Modification codes. RESULTS: Of 906,187 pregnant women, G-HA was found in 56,813 (6.3%). During the observational periods, the G-HA ( +) group had a significantly higher risk of any stroke [adjusted hazard ratio (aHR) = 1.59, 95% confidence interval (CI): 1.30-1.95], ischemic stroke (aHR = 1.50, 95% CI: 1.12-2.01), hemorrhagic stroke (aHR = 1.63, 95% CI: 1.23-2.15), and intracerebral hemorrhage (aHR = 1.63, 95% CI: 1.19-2.23) than the G-HA (-) group. When analyzed considering the interaction with history of headache disorder, G-HA showed a significant association with hemorrhagic stroke, but lost its effect on ischemic stroke. CONCLUSIONS: We demonstrated that G-HA was associated with subsequent stroke occurrence after delivery. However, the relationship between G-HA and ischemic stroke is mitigated by a history of pre-pregnancy headache disorder.

Prediction of Amyloid ß-Positivity with both MRI Parameters and Cognitive Function Using Machine Learning.

Purpose: To investigate the MRI markers for the prediction of amyloid ß (Aß)-positivity in mild cognitive impairment (MCI) and Alzheimer's disease (AD), and to evaluate the differences in MRI markers between Aß-positive (Aß [+]) and -negative groups using the machine learning (ML) method. Materials and Methods: This study included 139 patients with MCI and AD who underwent amyloid PET-CT and brain MRI. Patients were divided into Aß (+) (n = 84) and Aß-negative (n = 55) groups. Visual analysis was performed with the Fazekas scale of white matter hyperintensity (WMH) and cerebral microbleeds (CMB) scores. The WMH volume and regional brain volume were quantitatively measured. The multivariable logistic regression and ML using support vector machine, and logistic regression were used to identify the best MRI predictors of Aß-positivity. Results: The Fazekas scale of WMH (p = 0.02) and CMB scores (p = 0.04) were higher in Aß (+). The volumes of hippocampus, entorhinal cortex, and precuneus were smaller in Aß (+) (p < 0.05). The third ventricle volume was larger in Aß (+) (p = 0.002). The logistic regression of ML showed a good accuracy (81.1%) with mini-mental state examination (MMSE) and regional brain volumes. Conclusion: The application of ML using the MMSE, third ventricle, and hippocampal volume is helpful in predicting Aß-positivity with a good accuracy.

Kv7/KCNQ potassium channels in cortical hyperexcitability and juvenile seizure-related death in Ank2-mutant mice.

Autism spectrum disorders (ASD) represent neurodevelopmental disorders characterized by social deficits, repetitive behaviors, and various comorbidities, including epilepsy. ANK2, which encodes a neuronal scaffolding protein, is frequently mutated in ASD, but its in vivo functions and disease-related mechanisms are largely unknown. Here, we report that mice with Ank2 knockout restricted to cortical and hippocampal excitatory neurons (Ank2-cKO mice) show ASD-related behavioral abnormalities and juvenile seizure-related death. Ank2-cKO cortical neurons show abnormally increased excitability and firing rate. These changes accompanied decreases in the total level and function of the Kv7.2/KCNQ2 and Kv7.3/KCNQ3 potassium channels and the density of these channels in the enlengthened axon initial segment. Importantly, the Kv7 agonist, retigabine, rescued neuronal excitability, juvenile seizure-related death, and hyperactivity in Ank2-cKO mice. These results suggest that Ank2 regulates neuronal excitability by regulating the length of and Kv7 density in the AIS and that Kv7 channelopathy is involved in Ank2-related brain dysfunctions.

Long Sleep Duration and Dissatisfaction with Sleep Quality Are Associated with Ischemic Stroke in Young Patients.

INTRODUCTION: Suboptimal sleep duration and poor sleep quality have been proposed to increase stroke risk. However, their significance in young ischemic stroke is unclear. We aimed to investigate the importance of sleep duration and quality on young ischemic stroke patients. METHODS: A multicenter matched case-control study was performed to evaluate under-recognized risk factors in young (<45 years) ischemic stroke patients in 8 tertiary hospitals in Korea. A total of 225 patients and 225 age- and sex-matched controls were enrolled in the same period. Detailed information about patients' demographics, socioeconomic state, and traditional and nontraditional risk factors including sleep-related factors were obtained using structured questionnaires. Risk of ischemic stroke was estimated using conditional logistic regression analysis. RESULTS: Although average sleep duration was similar in patients and controls, patients were more likely to have long (≥9 h) or extremely short (<5 h) sleep durations. In addition, the proportion of subjects with dissatisfaction with sleep quality was higher in patients than controls (66.2 vs. 49.3%, p < 0.001). In multivariable conditional logistic regression analysis, long sleep duration (OR: 11.076, 95% CI: 1.819-67.446, p = 0.009) and dissatisfaction with sleep quality (OR: 2.116, 95% CI: 1.168-3.833, p = 0.013) were independently associated with risk of ischemic stroke. CONCLUSIONS: Long sleep duration and dissatisfaction with sleep quality may be associated with increased risk of ischemic stroke in young adults. Improving sleep habit or quality could be important for reducing the risk of ischemic stroke.

Sex differences and risk factors in recurrent ischemic stroke.

Introduction: Recurrent ischemic stroke (RIS) is associated with increased mortality and poor outcomes. Therefore, secondary prevention is critical for reducing the risk of recurrent stroke. Previous studies have found sex differences in risk factors in patients with first-ever stroke; however, the results have been inconsistent for recurrent stroke. Therefore, this study aimed to investigate whether there are significant sex differences in the clinical characteristics and risk factors for recurrent ischemic stroke. Methods: We retrospectively studied 787 patients with recurrent ischemic stroke after first-ever stroke confirmation using magnetic resonance imaging (MRI) after visiting a regional tertiary hospital between 2014 and 2020. Demographic characteristics, laboratory findings, and risk factors were compared between the male and female patients. In addition, multivariate logistic regression was performed to identify the independent factors associated with stroke recurrence in male patients. Results: Among the 787 patients, 466 (59.2%) were males. Males were younger than females (67.6 vs. 71.9 years). Females had higher rates of hypertension, diabetes mellitus, dyslipidemia, and overweight than those of males. However, the alcohol drinking and smoking rate were significantly higher in males than that in females. There were no statistically significant sex-based differences in the laboratory findings. Among males, hypertension, alcohol drinking, smoking and dyslipidemia was a significant risk factor for ischemic stroke recurrence. Conclusion: Hypertension and dyslipidemia were significant risk factors of recurrent ischemic stroke in both genders. Smoking and alcohol drinking were significant risk factors associated with ischemic stroke recurrence in males. Therefore, smoking cessation and alcohol abstinence are recommended after the first stroke to prevent recurrent ischemic stroke especially for males. Diabetes was a significant risk factor of ischemic stroke recurrence in females. More extensive studies are needed to understand the causal relationship of each factors with ischemic stroke recurrence according to sex differences and specification of preventive management is needed.

Two cases of Ramsay-Hunt syndrome following varicella zoster viral meningitis in young immunocompetent men: case reports.

BACKGROUND: Ramsay-Hunt syndrome (RHS) due to varicella zoster virus (VZV) infection is commonly reported in individuals aged at least 50 years or immunocompromised individuals. VZV infection may invade the central nervous system (CNS) and cause meningitis or encephalitis, which are more likely to occur in patients with chronic diseases such as diabetes and chronic renal failure. However, cases with VZV-induced concurrent RHS and CNS infections are rare. CASE PRESENTATION: Two young male patients, aged 32 and 43 years, with no underlying disease developed VZV meningitis, followed by RHS involving cranial nerves VII and VIII. Both patients presented with symptoms of peripheral facial palsy, and dizziness accompanied by tinnitus and hearing loss, which appeared several days after the onset of fever and headache. These symptoms were documented as facial neuropathy and sensorineural hearing loss in the electrophysiologic studies. Lymphocyte-dominant pleocytosis and VZV positivity were confirmed from cerebrospinal fluid examination and polymerase chain reaction, respectively. The patients were treated with intravenous acyclovir and oral steroids simultaneously. Following the treatment completion, both patients were relieved of their headaches and fever; however, facial palsy, dizziness, and tinnitus persisted. They were followed up at the outpatient clinic. CONCLUSION: These cases confirmed that RHS and CNS infections can co-exist even in young adults with normal immune function and more importantly, that CNS infection can precede RHS. Since early detection and treatment of RHS improve the prognosis, it is critical to closely monitor patients with VZV meningitis or encephalitis considering the possible superimposition of RHS.

Sudden unilateral hearing loss and vertigo following isolated cerebellar hypoperfusion without infarction due to vertebral artery dissection.

BACKGROUND: The definition of sudden sensorineural hearing loss (SSNHL) is broadly accepted as acute sensorineural hearing loss of more than 30 dB over at least three consecutive frequencies in a pure-tone audiogram (PTA). Acute audiovestibular loss is common with ischaemic stroke in the territory of the anterior inferior cerebellar artery (AICA). However, cases in which SSNHL and vertigo occur with hypoperfusion alone are very rare. We describe a patient who developed unilateral SSNHL and vertigo as initial symptoms caused by cerebellar hypoperfusion by vertebral artery (VA) dissection without the occurrence of infarction. CASE PRESENTATION: A 51-year-old man suddenly developed acute hearing loss (AHL) in his left ear and vertigo. On neurological examination, he had vibration-induced right-beating nystagmus and left-beating nystagmus after a head-shaking test. Additionally, he had apogeotropic nystagmus during head turns to either side. The head impulse test (HIT) was normal. PTA showed mild unilateral SSNHL in the left ear. Diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) showed territorial perfusion deficits in the left posterior inferior cerebellar artery (PICA) and anterior inferior cerebellar artery (AICA) without infarction. Two months later, the patient had no vertigo but still had hearing impairment in his left ear. A follow-up PTA documented persistent unilateral SSNHL in the left ear. Additionally, perfusion computed tomography (CT) showed that perfusion deficits remained in the left cerebellum along the PICA and AICA territories. CONCLUSIONS: Our case highlights a case of AHL and vertigo presented by isolated cerebellar hypoperfusion without infarction. It is necessary to consider the possibility of a central cause in patients with AHL and vertigo, and it is important to confirm this possibility through brain magnetic resonance imaging (MRI), including PWI, and magnetic resonance angiography (MRA).

Chronic Headache Attributed to Vertebrobasilar Insufficiency.

Vertebrobasilar insufficiency, a condition characterized by poor blood flow to the posterior portion of the brain, can cause headaches. However, the exact underlying mechanism is not yet fully understood. The patient enrolled in our study reported experiencing intermittent headaches radiating from the left shoulder, similar to chronic tension-type headaches. His aggravated headache and severe left vertebral artery stenosis were detected by brain computed tomography angiography. Stent insertion successfully expanded the patient's narrowed left vertebral artery orifice. Subsequently, the patient's headaches improved without recurrence during the one-year follow-up period. In summary, chronic headaches attributed to vertebrobasilar insufficiency in this study, improved after stent insertion to reverse severe left vertebral artery stenosis.

Association between Early Phase Serum Lactate Levels and Occurrence of Delayed Neuropsychiatric Sequelae in Adult Patients with Acute Carbon Monoxide Poisoning: A Systematic Review and Meta-Analysis.

The primary goal of treating carbon monoxide (CO) poisoning is preventing or minimizing the development of delayed neuropsychiatric sequelae (DNS). Therefore, screening patients with a high probability for the occurrence of DNS at the earliest is essential. However, prognostic tools for predicting DNS are insufficient, and the usefulness of the lactate level as a predictor is unclear. This systematic review and meta-analysis investigated the association between early phase serum lactate levels and the occurrence of DNS in adult patients with acute CO poisoning. Observational studies that included adult patients with CO poisoning and reported initial lactate concentrations were retrieved from the Embase, MEDLINE, Google Scholar and six domestic databases (KoreaMED, KMBASE, KISS, NDSL, KISTi and RISS) in January 2022. Lactate values were collected as continuous variables and analyzed using standardized mean differences (SMD) using a random-effect model. The risk of bias was evaluated using the Quality in Prognosis Studies (QUIPS) tool, and subgroup, sensitivity and meta regression analyses were performed. Eight studies involving a total of 1350 patients were included. The early phase serum lactate concentration was significantly higher in the DNS group than in the non-DNS group in adult patients with acute CO poisoning (8 studies; SMD, 0.31; 95% CI, 0.11−0.50; I2 = 44%; p = 0.002). The heterogeneity decreased to I2 = 8% in sensitivity analysis (omitting Han2021; 7 studies; SMD, 0.38; 95% CI, 0.23−0.53; I2 = 8%; p < 0.001). The risk of bias was assessed as high in five studies. The DNS group was associated with significantly higher lactate concentration than that in the non-DNS group.

Longitudinal intravital imaging of cerebral microinfarction reveals a dynamic astrocyte reaction leading to glial scar formation.

Cerebral microinfarct increases the risk of dementia. But how microscopic cerebrovascular disruption affects the brain tissue in cellular-level are mostly unknown. Herein, with a longitudinal intravital imaging, we serially visualized in vivo dynamic cellular-level changes in astrocyte, pericyte and neuron as well as microvascular integrity after the induction of cerebral microinfarction for 1 month in mice. At day 2-3, it revealed a localized edema with acute astrocyte loss, neuronal death, impaired pericyte-vessel coverage and extravascular leakage of 3 kDa dextran (but not 2 MDa dextran) indicating microinfarction-related blood-brain barrier (BBB) dysfunction for small molecules. At day 5, the local edema disappeared with the partial restoration of microcirculation and recovery of pericyte-vessel coverage and BBB integrity. But brain tissue continued to shrink with persisted loss of astrocyte and neuron in microinfarct until 30 days, resulting in a collagen-rich fibrous scar surrounding the microinfarct. Notably, reactive astrocytes expressing glial fibrillary acidic protein (GFAP) appeared at the peri-infarct area early at day 2 and thereafter accumulated in the peri-infarct until 30 days, inducing glial scar formation in cerebral cortex. Our longitudinal intravital imaging of serial microscopic neurovascular pathophysiology in cerebral microinfarction newly revealed that astrocytes are critically susceptible to the acute microinfarction and their reactive response leads to the fibrous glial scar formation.

Arterial spin labeling signal ratio between the lesion and contralateral sides for evaluation of acute middle cerebral artery infarct.

ABSTRACT: The purpose of our study was to differentiate arterial transit artifact from post-recanalization luxury perfusion on arterial spin labeling (ASL) image, and obtain the relationship between ASL signal intensity and clinical outcomes in patients with acute ischemic stroke.Thirty-five subjects with an acute middle cerebral artery (MCA) infarct were enrolled (18 with recanalized and 17 with non-recanalized MCAs). ASL images were obtained using pseudo-continuous ASL technique with 1600 ms (millisecond) of post-label delay within 3 days from symptom onset. Signal intensities on color ASL images were classified as high, intermediate, and poor grade visually. The ratio of maximum ASL signal between the ischemic area and contralateral side was calculated and compared between patients with and without MCA recanalization. Among patients with non-recanalized MCA, ASL signal ratios were compared between patients with and without hyperintense vessel sign on fluid attenuated inversion recovery (FLAIR). Also, correlation between the ASL signal ratio and National Institutes of Health Stroke Scale (NIHSS) score was evaluated.High or intermediate grade on color ASL images were more frequently found in patients with recanalized MCA (P < .01). Patients with non-recanalized MCA had higher ASL signal ratio in overall ASL signal grade (P = .010) and intermediate grade (P = .011). Among patients with non-recanalized MCA, those with hyperintense vessel sign on FLAIR had higher ASL signal ratios (P = .049). ASL signal ratio was negatively correlated with both initial (P = .023) and final (P = .003) NIHSS scores.The ASL signal ratio could help to differentiate between the pial collaterals and post-recanalization luxury perfusion. A higher ASL ratio was related with the hyperintense vessel sign on FLAIR and lower NIHSS score.

High-fidelity optical diffraction tomography of live organisms using iodixanol refractive index matching.

Optical diffraction tomography (ODT) enables the three-dimensional (3D) refractive index (RI) reconstruction. However, when the RI difference between a sample and a medium increases, the effects of light scattering become significant, preventing the acquisition of high-quality and accurate RI reconstructions. Herein, we present a method for high-fidelity ODT by introducing non-toxic RI matching media. Optimally reducing the RI contrast enhances the fidelity and accuracy of 3D RI reconstruction, enabling visualization of the morphology and intra-organization of live biological samples without producing toxic effects. We validate our method using various biological organisms, including C. albicans and C. elegans.

Global Differences in Risk Factors, Etiology, and Outcome of Ischemic Stroke in Young Adults-A Worldwide Meta-analysis: The GOAL Initiative.

BACKGROUND AND OBJECTIVES: There is a worldwide increase in the incidence of stroke in young adults, with major regional and ethnic differences. Advancing knowledge of ethnic and regional variation in causes and outcomes will be beneficial in implementation of regional health care services. We studied the global distribution of risk factors, causes, and 3-month mortality of young patients with ischemic stroke, by performing a patient data meta-analysis from different cohorts worldwide. METHODS: We performed a pooled analysis of individual patient data from cohort studies that included consecutive patients with ischemic stroke aged 18-50 years. We studied differences in prevalence of risk factors and causes of ischemic stroke between different ethnic and racial groups, geographic regions, and countries with different income levels. We investigated differences in 3-month mortality by mixed-effects multivariable logistic regression. RESULTS: We included 17,663 patients from 32 cohorts in 29 countries. Hypertension and diabetes were most prevalent in Black (hypertension, 52.1%; diabetes, 20.7%) and Asian patients (hypertension 46.1%, diabetes, 20.9%). Large vessel atherosclerosis and small vessel disease were more often the cause of stroke in high-income countries (HICs; both p < 0.001), whereas "other determined stroke" and "undetermined stroke" were higher in low and middle-income countries (LMICs; both p < 0.001). Patients in LMICs were younger, had less vascular risk factors, and despite this, more often died within 3 months than those from HICs (odds ratio 2.49; 95% confidence interval 1.42-4.36). DISCUSSION: Ethnoracial and regional differences in risk factors and causes of stroke at young age provide an understanding of ethnic and racial and regional differences in incidence of ischemic stroke. Our results also highlight the dissimilarities in outcome after stroke in young adults that exist between LMICs and HICs, which should serve as call to action to improve health care facilities in LMICs.