Association Between Electronic Device Use at Bedtime and COVID-19 Vaccine-Related Adverse Events During the COVID-19 Pandemic in Korean Adults: A Nationwide Cross-Sectional Population-Based Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to heightened mood disturbances linked to increased electronic device use at bedtime (EUB). General anxiety may contribute to an increased likelihood of experiencing nocebo responses, which have been reported to be associated with COVID-19 vaccine-related adverse events (CAEs). However, no related studies have been conducted to examine this association to date. METHODS: We executed a nationwide cross-sectional study to explore these correlations during the pandemic. Using data from the 2022 National Sleep Survey of South Korea, we analyzed the sleep health of 4,000 adults aged 20-69 years between January and February 2022. Shift workers and those with severe sleep disorders were excluded. Participants with EUB more than four days a week were labeled as high frequency EUB, and those reporting CAEs after both vaccine doses were marked as having a presence of CAEs. The survey also included details about anthropometric data, socioeconomic status, and sleep status. RESULTS: Of the 3,702 participants, 92.6% had received two or more vaccine doses, with 41.2% experiencing CAEs. Furthermore, 73.7% had a high EUB frequency. Factors associated with CAE reporting included younger age, female sex, and high EUB frequency, while heavy alcohol use was found to be less likely to be associated with CAE reporting. Notably, a high EUB frequency was significantly associated with reported CAEs (odds ratio, 1.223; 95% confidence interval, 1.028-1.455; P = 0.023). CONCLUSION: A nationwide online survey conducted in South Korea during the pandemic found that individuals who engaged in the relatively frequent use of electronic devices during bedtime had worse sleep quality and increased COVID-19-related adverse events compared with those using these devices less frequently. These findings have the potential to enhance our understanding of the impact of the use of electronic devices at bedtime on health.

Older adult-onset Alexander disease with atypical clinicoradiological features: a case report.

Alexander disease (AxD) is a rare autosomal dominant astrogliopathy caused by mutations in the gene encoding for glial fibrillary acidic protein. AxD is divided into two clinical subtypes: type I and type II AxD. Type II AxD usually manifests bulbospinal symptoms and occurs in the second decade of life or later, and its radiologic features include tadpole-like appearance of the brainstem, ventricular garlands, and pial signal changes along the brainstem. Recently, eye-spot signs in the anterior medulla oblongata (MO) have been reported in patients with elderly-onset AxD. In this case, an 82-year-old woman presented with mild gait disturbance and urinary incontinence without bulbar symptoms. The patient died 3 years after symptom onset as a result of rapid neurological deterioration after a minor head injury. MRI showed signal abnormalities resembling angel wings in the middle portion of the MO along with hydromyelia of the cervicomedullary junction. Herein, we report the case of this patient with older adult-onset AxD with an atypical clinical course and distinctive MRI findings.

Clinical analysis in patients with SPG11 hereditary spastic paraplegia.

Background: To analyze the clinical phenotype of hereditary spastic paraplegia (HSP) caused by SPG11 mutations (SPG11-HSP). Methods: Among the 17 patients with sporadic HSP who performed whole exome sequencing analysis, six were diagnosed with SPG11-HSP. The clinical and radiologic findings and the results of the electrodiagnostic and neuropsychologic tests were reviewed retrospectively. Results: The median age at onset was 16.5 years (range, 13-38 years). Progressive spastic paraparesis was a core feature, and the median spastic paraplegia rating scale score was 24/52 (range, 16-31 points). Additional major symptoms were pseudobulbar dysarthria, intellectual disability, bladder dysfunction, and being overweight. Minor symptoms included upper limbs rigidity and sensory axonopathy. The median body mass index was 26.2 kg/m2 (range, 25.2-32.3 kg/m2). The thin corpus callosum (TCC) was predominant at the rostral body or anterior midbody, and the ears of the lynx sign was seen in all. The follow-up MRI showed the worsening of periventricular white matter (PVWM) signal abnormalities with ventricular widening or the extension of the TCC. Motor evoked potentials (MEP) to the lower limbs showed an absent central motor conduction time (CMCT) in all subjects. The upper limb CMCT was initially absent in three subjects, although it became abnormal in all at the follow-up. The mini-mental state examination median score was 27/30 (range, 26-28) with selective impairment of the attention/calculation domain. The median score of the full-scale intelligence quotient was 48 (range, 42-72) on the Wechsler Adult Intelligence Scale test. Conclusion: Attention/calculation deficits and being overweight as well as pseudobulbar dysarthria were common additional symptoms in patients with SPG11-HSP. The rostral body and anterior midbody of the corpus callosum were preferentially thinned, especially in the early stage of the disease. The TCC, PVWM signal changes, and MEP abnormality worsened as the disease progressed.

Multidimensional Early Prediction Score for Drug-Resistant Epilepsy.

BACKGROUND AND PURPOSE: Achieving favorable postoperative outcomes in patients with drug-resistant epilepsy (DRE) requires early referrals for preoperative examinations. The purpose of this study was to investigate the possibility of a user-friendly early DRE prediction model that is easy for nonexperts to utilize. METHODS: A two-step genotype analysis was performed, by applying 1) whole-exome sequencing (WES) to the initial test set (n=243) and 2) target sequencing to the validation set (n=311). Based on a multicenter case-control study design using the WES data set, 11 genetic and 2 clinical predictors were selected to develop the DRE risk prediction model. The early prediction scores for DRE (EPS-DRE) was calculated for each group of the selected genetic predictors (EPS-DREgen), clinical predictors (EPS-DREcln), and two types of predictor mix (EPS-DREmix) in both the initial test set and the validation set. RESULTS: The multidimensional EPS-DREmix of the predictor mix group provided a better match to the outcome data than did the unidimensional EPS-DREgen or EPS-DREcln. Unlike previous studies, the EPS-DREmix model was developed using only 11 genetic and 2 clinical predictors, but it exhibited good discrimination ability in distinguishing DRE from drug-responsive epilepsy. These results were verified using an unrelated validation set. CONCLUSIONS: Our results suggest that EPS-DREmix has good performance in early DRE prediction and is a user-friendly tool that is easy to apply in real clinical trials, especially by nonexperts who do not have detailed knowledge or equipment for assessing DRE. Further studies are needed to improve the performance of the EPS-DREmix model.

A Rapid and Noninvasive Method That Extracts Polymerase Chain Reaction-Ready Genomic DNA from Adult Zebrafish.

Genotyping usually entails analysis of the products of polymerase chain reaction (PCR) carried out with genomic DNA (gDNA) as template, and is employed for validation of mutant or transgenic organisms. For genotyping of adult zebrafish, gDNA is often extracted from clipped caudal fin or skin mucus through either alkaline lysis using NaOH or proteinase K (PK) treatment. Further purification of the gDNA using ethanol precipitation was optional. To develop a rapid and noninvasive method that extracts PCR-ready gDNA from adult zebrafish, we combined skin swabbing with PK treatment and demonstrated its efficiency. This method could be applied to a wide range of fish.

A Genotype-Phenotype Study of Multiple Hereditary Exostoses in Forty-Three Patients.

Multiple hereditary exostoses (MHE) is a rare autosomal dominant skeletal disorder with a variety of clinical manifestations. We aimed to evaluate the general clinical phenotypic severity of MHE using our own scoring system and analyzed the risk factors associated with severe clinical phenotypes. In this study, 43 patients from 30 families were analyzed. The mutations were identified by direct sequencing of polymerase chain reaction-amplified genomic DNA or by multiplex ligation-dependent probe amplification. According to a new scoring system devised by the authors, the severity of the phenotype was assessed as mild, moderate, or severe based on the deformity of each segment, number of exostoses, leg length discrepancy, and functional limitations. Of 43 patients from 30 families, 39 patients (90.7%) and 24 families (80%) presented with EXT1 or EXT2 mutations. Patients with EXT1 mutations had a significantly worse phenotype than that of patients with EXT2 mutations or without any detectable mutation. The mean clinical score of patients with an EXT1 mutation (5.76; range, 2.0-8.0; SD = 1.60) was higher than that of patients with an EXT2 mutation (4.06; range, 2.0-7.0; SD = 1.47) or of those without any detectable mutation (4.63; range, 3.0-6.0; SD = 1.44; p = 0.005). According to our classification system, more patients with EXT1 mutations had 'severe disease' than those with EXT2 mutations. Deformity scores were also higher in patients with EXT1 mutations (p = 0.018). In the multivariate analysis, the deformity score was found to be associated with the 'severe' class (p = 0.031). In conclusion, 90.7% of patients with MHE showed EXT mutations. Our scoring system showed reliable results. We suggest that the extent of deformity is an important factor in determining the phenotype of MHE and close monitoring for the development of severe disease is recommended in patients with high deformity scores.

A novel in-frame GFAP p.E138_L148del mutation in Type II Alexander disease with atypical phenotypes.

Alexander disease (AxD) is a neurodegenerative astrogliopathy caused by mutation in the glial fibrillary acidic protein (GFAP) gene. A 42-year-old Korean man presented with temporary gait disturbance and psychiatric regression after a minor head trauma in the absence of bulbar symptoms and signs. Magnetic resonance images of the brain and spinal cord showed significant atrophy of the medulla oblongata and the entire spinal cord as well as contrast-enhanced T2 hypointensity in the basal ganglia. DNA sequencing revealed a novel 33-bp in-frame deletion mutation (p.Glu138_Leu148del) within the 1B rod domain of GFAP, which was predicted to be deleterious by PROVEAN analysis. To test whether the deletion mutant is disease-causing, we performed in vitro GFAP assembly and sedimentation assays, and GFAP aggregation assays in human adrenal carcinoma SW13 (Vim-) cells and rat primary astrocytes. All the assays revealed that GFAP p.Glu138_Leu148del is aggregation prone. Based on these findings, we diagnosed the patient with Type II AxD. This is a report that demonstrates the pathogenicity of InDel mutation of GFAP through functional studies. This patient's atypical presentation as well as the discrepancy between clinical symptoms and radiologic findings may extend the scope of AxD.

Characteristics of patients with meningitis after lumbar epidural steroid injection.

To investigate the clinical, laboratory, and radiological features of meningitis after lumbar epidural steroid injection (M-ESI) without accompanying spinal infection, data of patients with meningitis admitted between January 2014 and December 2021 in a single center were retrospectively reviewed. Among them, patients with a recent history of lumbar ESI were identified, and their medical records were collected. Patients with concomitant infections other than meningitis, including spinal epidural abscess, were excluded. Seven patients with M-ESI were identified. All patients presented with headache and fever without focal neurological deficits, and headache developed shortly after a procedure (median, 4 hours). Cerebrospinal fluid (CSF) analysis showed neutrophilic pleocytosis (median, 6729/µL), elevated protein level (median, 379.1 mg/dL), decreased ratio of CSF glucose to serum glucose (median, 0.29), and elevated lactate level (median, 8.64 mmol/L). Serum level of C-reactive protein was elevated in 6, but serum procalcitonin level was within normal range. No causative pathogen was identified in the microbiological studies. The most frequent radiologic feature was sulcal hyperintensity on fluid-attenuated inversion recovery images (57%), followed by pneumocephalus (43%). Symptoms subsided in a short period (median, 1 day) after initiating treatment with antibiotics and adjuvant intravenous corticosteroids. None of the patients experienced neurological sequelae. Though the cardinal symptoms and CSF findings of M-ESI were comparable to those of bacterial meningitis, M-ESI seems to have distinctive characteristics regarding the clinical course, laboratory parameters, and pneumocephalus.

Cerebellar infarction presenting with isolated positional vertigo: differentiating factors for benign paroxysmal positional vertigo.

BACKGROUND: Isolated central positional vertigo (CPV) due to cerebellar infarction is often difficult to differentiate from benign paroxysmal positional vertigo (BPPV). Here, we aimed to evaluate whether vascular risk factors and serum vitamin D level can differentiate between positional vertigo types. METHODS: A total of 78 consecutive patients were consecutively enrolled from January 2017. All CPV patients had a National Institutes of Health Stroke Scale score of 0 and cerebellar infarctions confirmed by brain MR imaging. Vascular risk factors and serum 25-hydroxyvitamin D levels were compared between the two groups of patients. RESULTS: The proportion of men was higher in the CPV than in the BPPV group (p = 0.004). Atrial fibrillation was common in the CPV group on univariate analysis (p = 0.046). However, there were no independent differentiating factors between the two groups. The proportion of patients according to the number of risk factors was significantly different between the two groups (linear by linear association test, p = 0.02). The mean serum 25-hydroxyvitamin D level did not differ. Also, the proportions of vitamin D insufficiency and deficiency did not differ significantly between the two groups. CONCLUSIONS: Increased number of vascular risk factors including male sex suggested more CPV than BPPV. However, the serum vitamin D level was below the normal range in both groups. Our results demonstrate that serum vitamin D level has little value in the differential diagnosis of positional vertigo. Efforts to identify differentiating factors are warranted, and accumulating evidences including our research may lead to a diagnostic algorithm for isolated positional vertigo.

Fulminant Course of Neuromyelitis Optica in a Patient With Anti-MDA5 Antibody-Positive Dermatomyositis: A Case Report.

Anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody is a myositis-specific marker detected in clinically amyopathic dermatomyositis (DM). DM with anti-MDA5 antibody can be accompanied by rapidly progressive interstitial lung disease (RP-ILD) and other autoimmune disorders. Until now, only one case of neuromyelitis optica (NMO) with anti-MDA5-positive DM has been reported worldwide, in which the patient achieved a favorable outcome with intensive immunotherapy. We report a case of NMO in a patient with anti-MDA5-positive DM complicated by ILD and rheumatoid arthritis. Our patient experienced a fulminant course of NMO, rather than RP-ILD, in the presence of hyperferritinemia, which resulted in profound neurological sequelae despite immunotherapy including rituximab.

Family cohesion is differently associated with felt stigma depending on enacted stigma in adults with epilepsy.

PURPOSE: There have been little researches examining the role of family functioning on psychological outcomes in the field of adult epilepsy. We determined whether family functioning is correlated with felt stigma in adults with epilepsy. METHODS: In this cross-sectional study, adults with epilepsy and their caregivers were recruited. Data were collected using the Family Adaptability and Cohesion Evaluation Scale (FACES) III, the Family adaptation, partnership, growth, affection, and resolve (APGAR) questionnaire, the Stigma Scale for Epilepsy (SS-E), the modified questionnaire for episodes of discrimination, and the Beck Depression Inventory. Family functioning was measured by the caregivers. RESULTS: A total of 273 adult patients and their primary caregivers were included. Multivariate logistic analyses showed that family cohesion and excellent family functioning were negatively correlated with felt stigma after controlling for confounding variables. Enacted stigma, depressive symptoms, and university education were also significant. Interaction between enacted stigma and family cohesion on felt stigma was significant (p = 0.049). Family cohesion was negatively correlated with felt stigma only in the patients with enacted stigma (p = 0.011). CONCLUSIONS: Family functioning especially family cohesion may have protective effects against development of felt stigma in adults with epilepsy. Such protecting effects against felt stigma may be different according to enacted stigma. This understanding is helpful for developing effective psychosocial interventions to reduce felt stigma in patients with epilepsy.

Wnt-PLC-IP3-Connexin-Ca2+ axis maintains ependymal motile cilia in zebrafish spinal cord.

Ependymal cells (ECs) are multiciliated neuroepithelial cells that line the ventricles of the brain and the central canal of the spinal cord (SC). How ependymal motile cilia are maintained remains largely unexplored. Here we show that zebrafish embryos deficient in Wnt signaling have defective motile cilia, yet harbor intact basal bodies. With respect to maintenance of ependymal motile cilia, plcδ3a is a target gene of Wnt signaling. Lack of Connexin43 (Cx43), especially its channel function, decreases motile cilia and intercellular Ca2+ wave (ICW) propagation. Genetic ablation of cx43 in zebrafish and mice diminished motile cilia. Finally, Cx43 is also expressed in ECs of the human SC. Taken together, our findings indicate that gap junction mediated ICWs play an important role in the maintenance of ependymal motile cilia, and suggest that the enhancement of functional gap junctions by pharmacological or genetic manipulations may be adopted to ameliorate motile ciliopathy.

ACOX3 Dysfunction as a Potential Cause of Recurrent Spontaneous Vasospasm of Internal Carotid Artery.

Recurrent spontaneous vasospasm of the extracranial internal carotid artery (RSV-eICA) is a rarely recognized cause of ischemic stroke in young adults. However, its pathophysiology remains largely unknown. Through whole-exome sequencing of the ACOX3 gene of two dizygotic Korean twin brothers affected by RSV-eICA, we identified two compound heterozygous missense variants c.235 T > G (p.F79 V) and c.665G > A (p.G222E). In silico analysis indicated that both variants were classified as pathogenic. In vitro ACOX3 enzyme assay indicated practically no enzyme activity in both F79 V and G222E mutants. To determine the effect of the mutants on vasospasm, we used a collagen contraction assay on human aortic smooth muscle cells (HASMC). Carbachol, a cholinergic agonist, induces contraction of HASMC. Knockdown of ACOX3 in HASMC, using siRNA, significantly repressed HASMC contraction triggered by carbachol. The carbachol-induced HASMC contraction was restored by transfection with plasmids encoding siRNA-resistant wild-type ACOX3, but not by transfection with ACOX3 G222E or by co-transfection with ACOX3 F79 V and ACOX3 G222E, indicating that the two ACOX3 mutants suppress carbachol-induced HASMC contraction. We propose that an ACOX3 dysfunction elicits a prolonged loss of the basal aortic myogenic tone. As a result, smooth muscles of the ICA's intermediate segment, in which the sympathetic innervation is especially rich, becomes hypersensitive to sympathomimetic stimuli (e.g., heavy exercise) leading to a recurrent vasospasm. Therefore, ACOX3 dysfunction would be a causal mechanism of RSV-eICA. For the first time, we report the possible involvement of ACOX3 in maintaining the basal myogenic tone of human arterial smooth muscle.

A zebrafish model of nondystrophic myotonia with sodium channelopathy.

Nondystrophic myotonias are disorders of Na+ (Nav1.4 or SCN4A) and Cl- (CLCN1) channels in skeletal muscles, and frequently show phenotype heterogeneity. The molecular mechanism underlying their pathophysiology and phenotype heterogeneity remains unclear. As zebrafish models have been recently exploited for studies of the pathophysiology and phenotype heterogeneity of various human genetic diseases, a zebrafish model may be useful for delineating nondystrophic myotonias. Here, we generated transgenic zebrafish expressing a human mutant allele of SCN4A, referred to as Tg(mylpfa:N440K), and needle electromyography revealed increased number of myotonic discharges and positive sharp waves in the muscles of Tg(mylpfa:N440K) than in controls. In addition, forced exercise test at a water temperature of 24 °C showed a decrease in the distance moved, time spent in and number of visits to the zone with stronger swimming resistance. Finally, a forced exercise test at a water temperature of 18 °C exhibited a higher number of dive-bombing periods and drifting-down behavior than in controls. These findings indicate that Tg(mylpfa:N440K) is a good vertebrate model of exercise- and cold-induced human nondystrophic myotonias. This zebrafish model may contribute to provide insight into the pathophysiology of myotonia in sodium channelopathy and could be used to explore a new therapeutic avenue.

Genetic characteristics of non-familial epilepsy.

BACKGROUND: Knowledge of the genetic etiology of epilepsy can provide essential prognostic information and influence decisions regarding treatment and management, leading us into the era of precision medicine. However, the genetic basis underlying epileptogenesis or epilepsy pharmacoresistance is not well-understood, particularly in non-familial epilepsies with heterogeneous phenotypes that last until or start in adulthood. METHODS: We sought to determine the contribution of known epilepsy-associated genes (EAGs) to the causation of non-familial epilepsies with heterogeneous phenotypes and to the genetic basis underlying epilepsy pharmacoresistance. We performed a multi-center study for whole exome sequencing-based screening of 178 selected EAGs in 243 non-familial adult patients with primarily focal epilepsy (122 drug-resistant and 121 drug-responsive epilepsies). The pathogenicity of each variant was assessed through a customized stringent filtering process and classified according to the American College of Medical Genetics and Genomics guidelines. RESULTS: Possible causal genetic variants of epilepsy were uncovered in 13.2% of non-familial patients with primarily focal epilepsy. The diagnostic yield according to the seizure onset age was 25% (2/8) in the neonatal and infantile period, 11.1% (14/126) in childhood and 14.7% (16/109) in adulthood. The higher diagnostic yields were from ion channel-related genes and mTOR pathway-related genes, which does not significantly differ from the results of previous studies on familial or early-onset epilepsies. These potentially pathogenic variants, which were identified in genes that have been mainly associated with early-onset epilepsies with severe phenotypes, were also linked to epilepsies that start in or last until adulthood in this study. This finding suggested the presence of one or more disease-modifying factors that regulate the onset time or severity of epileptogenesis. The target hypothesis of epilepsy pharmacoresistance was not verified in our study. Instead, neurodevelopment-associated epilepsy genes, such as TSC2 or RELN, or structural brain lesions were more strongly associated with epilepsy pharmacoresistance. CONCLUSIONS: We revealed a fraction of possible causal genetic variants of non-familial epilepsies in which genetic testing is usually overlooked. In this study, we highlight the importance of earlier identification of the genetic etiology of non-familial epilepsies, which leads us to the best treatment options in terms of precision medicine and to future neurobiological research for novel drug development. This should be considered a justification for physicians determining the hidden genetics of non-familial epilepsies that last until or start in adulthood.

Optimal blood pressure after reperfusion therapy in patients with acute ischemic stroke.

We investigated the relationship between the mean blood pressure (BP) at 24-72 h and the clinical outcomes after acute ischemic stroke (AIS) in patients treated with reperfusion therapy. The primary outcome was measured using the modified Rankin Scale (mRS) at 3 months after AIS, and was based on the mean systolic BP at 24-72 h post-AIS. Favorable outcome was defined as mRS scores of 0-2. A total of 1,540 patients treated with reperfusion therapy were enrolled in the study. Favorable outcomes occurred more frequently in patients with BP ≤ 130/80 mmHg, and the risks of symptomatic intracranial hemorrhage and early neurological deterioration were lower in this optimal BP group. Multivariable analysis showed a significant association between mean BP ≤ 130/80 mmHg at 24-72 h and favorable outcomes at 3 months after AIS (odds ratio 2.95, 95% confidence interval 2.32-3.77, p < 0.001). Prespecified subgroup analyses showed that BP ≤ 130/80 mmHg had a more significant impact on clinical outcome in patients with recanalization than in those without recanalization. These data indicate that a mean BP of ≤ 130/80 mmHg at 24-72 h post-AIS is independently associated with favorable outcomes in patients treated with reperfusion therapy, particularly in those with recanalization.

Impact of Visceral Adipose Tissue on Clinical Outcomes After Acute Ischemic Stroke.

Background and Purpose- The purpose of this study was to investigate the association between adiposity using adipose tissue imaging and stroke outcomes in acute ischemic stroke patients treated with intravenous thrombolysis. Methods- A total of 127 patients with acute ischemic stroke treated with intravenous thrombolysis who underwent abdominal computed tomography on admission were enrolled in this prospective cohort study. Patients were grouped according to their visceral adipose tissue (VAT) proportion tertile. The primary outcome was measured using the modified Rankin Scale 3 months after symptom onset. Favorable and excellent outcomes were defined as modified Rankin Scale scores of 0 to 2 and 0 to 1, respectively. Results- As VAT proportion tertile increased, the number of patients exhibiting a favorable or excellent outcome decreased. In the final multivariable analysis after adjustments for confounders, patients in the highest VAT proportion tertile showed a decreased probability of a favorable and excellent outcome compared with those in the lowest tertile (odds ratio=0.18; 95% CI, 0.05-0.60; P=0.005 and odds ratio=0.13; 95% CI, 0.02-0.64; P=0.012, respectively). Obese patients (body mass index ≥25) also showed an excellent outcome compared with nonobese patients (odds ratio=4.88; 95% CI, 1.47-7.85; P=0.011). Among obese patients, those with an excellent outcome presented a significantly lower VAT proportion than those without (38.2% versus 46.1%, P=0.006). Conclusions- Results of this study indicate that low visceral abdominal fat proportion is associated with a favorable and excellent outcome in acute ischemic stroke patients treated with intravenous thrombolysis. Better clinical outcomes in obese patients were also associated with a lower proportion of VAT.

HbA1c (Glycated Hemoglobin) Levels and Clinical Outcome Post-Mechanical Thrombectomy in Patients With Large Vessel Occlusion.

Background and Purpose- We analyzed the relationship between HbA1c (glycated hemoglobin) levels and clinical outcomes in patients with large vessel occlusion treated with mechanical thrombectomy (MT). Methods- A total of 534 patients with acute ischemic stroke (AIS) treated with MT were enrolled in this prospective cohort study. The primary outcome measured was the modified Rankin Scale score at 3 months, according to HbA1c level. High HbA1c levels were defined as a plasma level of HbA1c >6.5%. Favorable outcomes were defined as functional independence, with modified Rankin Scale scores of 0 to 2. Secondary functional outcomes included mortality, early clinical outcomes, and intracranial hemorrhage. Results- The number of patients with a favorable outcome was significantly lower in patients with HbA1c >6.5% than in those with HbA1c ≤6.5% (28.8% versus 42.1%; P=0.006). In multivariate analysis, high HbA1c levels (especially >7.0% HbA1c) were significantly associated with poor functional outcomes 3 months after AIS in patients with large vessel occlusion treated with MT. High HbA1c was also significantly associated with increased mortality and worse early clinical outcomes after AIS in patients treated with MT. Subgroup analyses showed that HbA1c >6.5% was associated with significantly lower odds of functional independence at 3 months after AIS, when comparing the recanalized group with nonrecanalized patients. Conclusions- These results suggest that high HbA1c level is an independent predictor of a poor outcome at 3 months after AIS in patients with large vessel occlusion treated with MT, particularly in those with recanalization, and may augment the risk of mortality and early clinical worsening after AIS.