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Importance: A proportion of people with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) have a relapsing disease course and persistent anti-myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) seropositivity. Few studies have investigated whether treatment of the first MOGAD attack is associated with the long-term disease course and/or MOG-IgG seronegative conversion. Objective: To investigate the association of time to treat the first acute MOGAD attack with relapse risk and MOG-IgG serostatus. Design, Setting, and Participants: This was a retrospective, nationwide, multicenter cohort study involving 14 secondary or tertiary hospitals in South Korea between November 2009 and August 2023. People with adult-onset MOGAD, who either had a relapse or were followed up for more than 12 months after disease onset and had a detailed medical record of their first attack, were included. Individuals were excluded for adolescent-onset MOGAD or short disease duration. Exposures: Patients were categorized based on the time to treat the first acute MOGAD attack: early (<5 days), intermediate (5-14 days), and late (not treated within 14 days). Main Outcomes and Measures: A multivariable analysis for clinical and treatment factors associated with relapsing disease course and/or MOG-IgG seronegative conversion. Further subgroup analyses were conducted among those without long-term nonsteroidal immunosuppressant (NSIS) maintenance treatment. Results: Among the 315 individuals screened, 75 were excluded. A total of 240 patients (median [IQR] age at onset, 40.4 [28.8-56.1] years; 125 female [52.1%]) with median (IQR) disease duration of 3.07 (1.95-6.15) years were included. A total of 110 of 240 patients (45.8%) relapsed after a median (IQR) of 0.45 (0.18-1.68) years, and 29 of 116 patients (25.0%) experienced a conversion to seronegative MOG-IgG. Both the time to treatment of the first MOGAD attack (late vs early: adjusted hazard ratio [aHR], 2.64; 95% CI, 1.43-4.84; P = .002; intermediate vs early: aHR, 2.02; 95% CI, 1.10-3.74; P = .02) and NSIS maintenance treatment (aHR, 0.24; 95% CI, 0.14-0.42; P < .001) were independently associated with the risk of relapse. In a subgroup without NSIS maintenance, the time to treat of the first MOGAD attack was still associated with higher risk of relapse (late vs early: aHR, 3.51; 95% CI, 1.64-7.50; P = .001; intermediate vs early: aHR, 2.68; 95% CI, 1.23-5.85; P = .01). Lastly, the time to treat of the first MOGAD attack was also associated with MOG-IgG seronegative conversion (early vs late: adjusted odds ratio, 7.04; 95% CI, 1.58-31.41; P = .01), whereas NSIS maintenance treatment was not. Conclusions and Relevance: Results of this cohort study suggest that early treatment of the first acute MOGAD attack was associated with a reduction in the proportion of relapsing disease course and an increase in the likelihood of MOG-IgG seronegative conversion. These data suggest that timing of acute phase treatment for the first MOGAD attack can be associated with the long-term prognosis and autoimmune status of patients.
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BACKGROUND AND PURPOSE: Visual perceptual learning (VPL) may improve visual field defects (VFDs) after chronic stroke, but the optimal training duration and location remain unknown. This prospective study aimed to determine the efficacy of 8 weeks of VFD-customized visual discrimination training in improving poststroke VFDs. METHODS: Prospectively enrolled patients with poststroke VFDs initially received no training for 8 weeks (no-training phase). They subsequently underwent our customized VPL program that included orientation-discrimination tasks in individualized blind fields and central letter-discrimination tasks three times per week for 8 weeks (training phase). We analyzed the luminance detection sensitivity and deviation as measured using Humphrey visual field tests before and after the no-training and training phases. The vision-related quality of life was assessed at baseline and at a 16-week follow-up using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25). RESULTS: Changes in mean total deviation (MTD) scores were greater during the training phase than during the no-training phase (defective hemifield, p=0.002; whole field, p=0.004). The MTD scores improved during the training phase (defective hemifield, p=0.004; whole field, p=0.016), but not during the no-training phase (defective hemifield, p=0.178; whole field, p=0.178). The difference between the improved and worsened areas (≥6 dB changes in luminance detection sensitivity) was greater during the training phase than during the no-training phase (p=0.009). The vision-specific social functioning subscore of the NEI-VFQ-25 improved after the 16-week study period (p=0.040). CONCLUSIONS: Our 8-week VFD-customized visual discrimination training protocol may effectively improve VFDs and vision-specific social functioning in chronic stroke patients.
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Cognitive impairment (CI) is prevalent in central nervous system demyelinating diseases, such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). We developed a novel tablet-based modified digital Symbol Digit Modalities Test (MD-SDMT) with adjustable protocols that feature alternating symbol-digit combinations in each trial, lasting one or two minutes. We assessed 144 patients (99 with MS and 45 with NMOSD) using both MD-SDMT protocols and the traditional paper-based SDMT. We also gathered participants' feedback through a questionnaire regarding their preferences and perceived reliability. The results showed strong correlations between MD-SDMT and paper-based SDMT scores (Pearsons correlation: 0.88 for 2 min; 0.85 for 1 min, both p < 0.001). Among the 120 respondents, the majority preferred the digitalized SDMT (55% for the 2 min, 39% for the 1 min) over the paper-based version (6%), with the 2 min MD-SDMT reported as the most reliable test. Notably, patients with NMOSD and older individuals exhibited a preference for the paper-based test, as compared to those with MS and younger patients. In summary, even with short test durations, the digitalized SDMT effectively evaluates cognitive function in MS and NMOSD patients, and is generally preferred over the paper-based method, although preferences may vary with patient characteristics.
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Esclerosis Múltiple , Neuromielitis Óptica , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Esclerosis Múltiple/psicología , Esclerosis Múltiple/fisiopatología , Neuromielitis Óptica/fisiopatología , Pruebas Neuropsicológicas , Disfunción Cognitiva/diagnóstico , Reproducibilidad de los Resultados , Anciano , Enfermedades Desmielinizantes , Encuestas y Cuestionarios , Adulto Joven , Computadoras de ManoRESUMEN
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.
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BACKGROUND: We determined whether the severity of sleep apnea increases the risk of mortality in patients with multiple system atrophy (MSA) with and without stridor. MethodsThis retrospective study included patients who underwent polysomnography within one year after diagnosis of probable MSA. Stridor, sleep apnea, and arousal from sleep were determined using full-night polysomnography. Disease severity was measured using the Unified MSA Rating Scale (UMSARS). Survival data were collected and analyzed using Cox regression analysis. RESULTS: Sixty-four patients with MSA were included. During a median follow-up of 34.5 months, 49 (76.6 %) patients died. Stridor was present in 56.3 % of patients. Patients with stridor had more severe sleep apnea and shorter sleep time than those without, but the hazard ratio (HR) for death did not differ between patients with and without stridor. Among patients without stridor, apnea-hypopnea index ≥30/h (HR, 6.850; 95 % confidence interval [CI], 1.983-23.664; p = 0.002) and a score of UMSARS I + II (HR, 1.080; 95 % CI, 1.040-1.121; p < 0.001) were independently associated with death. In contrast, among patients with stridor, frequent arousals from sleep (HR, 0.254; 95 % CI, 0.089-0.729; p = 0.011) were a significant factor associated with longer survival, while MSA-cerebellar type tended to be associated with poor survival (HR, 2.195; 95 % CI, 0.941-5.120; p = 0.069). CONCLUSION: The severity of sleep apnea might be a significant predictor of shorter survival in MSA patients without stridor, whereas frequent arousals from sleep might be a significant predictor for longer survival in MSA patients with stridor.
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Atrofia de Múltiples Sistemas , Polisomnografía , Índice de Severidad de la Enfermedad , Síndromes de la Apnea del Sueño , Humanos , Atrofia de Múltiples Sistemas/mortalidad , Atrofia de Múltiples Sistemas/complicaciones , Atrofia de Múltiples Sistemas/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Síndromes de la Apnea del Sueño/mortalidad , Síndromes de la Apnea del Sueño/complicaciones , Pronóstico , Ruidos Respiratorios/etiología , Ruidos Respiratorios/fisiopatología , Estudios de SeguimientoRESUMEN
BACKGROUND: Brain-derived exosomes circulate in the bloodstream and other bodily fluids, serving as potential indicators of neurological disease progression. These exosomes present a promising avenue for the early and precise diagnosis of neurodegenerative conditions. Notably, miRNAs found in plasma extracellular vesicles (EVs) offer distinct diagnostic benefits due to their stability, abundance, and resistance to breakdown. RESULTS: In this study, we introduce a method using transferrin conjugated magnetic nanoparticles (TMNs) to isolate these exosomes from the plasma of patients with neurological disorders. This TMNs technique is both quick (<35 min) and cost-effective, requiring no high-priced ingredients or elaborate equipment for EV extraction. Our method successfully isolated EVs from 33 human plasma samples, including those from patients with Parkinson's disease (PD), Multiple Sclerosis (MS), and Dementia. Using quantitative polymerase chain reaction (PCR) analysis, we evaluated the potential of 8 exosomal miRNA profiles as biomarker candidates. Six exosomal miRNA biomarkers (miR-195-5p, miR-495-3p, miR-23b-3P, miR-30c-2-3p, miR-323a-3p, and miR-27a-3p) were consistently linked with all stages of PD. SIGNIFICANCE: The TMNs method provides a practical, cost-efficient way to isolate EVs from biological samples, paving the way for non-invasive neurological diagnoses. Furthermore, the identified miRNA biomarkers in these exosomes may emerge as innovative tools for precise diagnosis in neurological disorders including PD.
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Exosomas , Nanopartículas de Magnetita , MicroARNs , Enfermedad de Parkinson , Transferrina , Humanos , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/sangre , Exosomas/química , MicroARNs/sangre , Nanopartículas de Magnetita/química , Transferrina/química , Encéfalo/metabolismo , Biomarcadores/sangre , Masculino , FemeninoRESUMEN
BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, patients with myasthenia gravis (MG) were more susceptible to poor outcomes owing to respiratory muscle weakness and immunotherapy. Several studies conducted in the early stages of the COVID-19 pandemic reported higher mortality in patients with MG compared to the general population. This study aimed to investigate the clinical course and prognosis of COVID-19 in patients with MG and to compare these parameters between vaccinated and unvaccinated patients in South Korea. METHODS: This multicenter, retrospective study, which was conducted at 14 tertiary hospitals in South Korea, reviewed the medical records and identified MG patients who contracted COVID-19 between February 2022 and April 2022. The demographic and clinical characteristics associated with MG and vaccination status were collected. The clinical outcomes of COVID-19 infection and MG were investigated and compared between the vaccinated and unvaccinated patients. RESULTS: Ninety-two patients with MG contracted COVID-19 during the study. Nine (9.8%) patients required hospitalization, 4 (4.3%) of whom were admitted to the intensive care unit. Seventy-five of 92 patients were vaccinated before contracting COVID-19 infection, and 17 were not. During the COVID-19 infection, 6 of 17 (35.3%) unvaccinated patients were hospitalized, whereas 3 of 75 (4.0%) vaccinated patients were hospitalized (P < 0.001). The frequencies of ICU admission and mechanical ventilation were significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.019 and P = 0.032, respectively). The rate of MG deterioration was significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.041). Logistic regression after weighting revealed that the risk of hospitalization and MG deterioration after COVID-19 infection was significantly lower in the vaccinated patients than in the unvaccinated patients. CONCLUSION: This study suggests that the clinical course and prognosis of patients with MG who contracted COVID-19 during the dominance of the omicron variant of COVID-19 may be milder than those at the early phase of the COVID-19 pandemic when vaccination was unavailable. Vaccination may reduce the morbidity of COVID-19 in patients with MG and effectively prevent MG deterioration induced by COVID-19 infection.
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Vacunas contra la COVID-19 , COVID-19 , Hospitalización , Miastenia Gravis , SARS-CoV-2 , Vacunación , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , COVID-19/complicaciones , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , República de Corea/epidemiología , Anciano , SARS-CoV-2/aislamiento & purificación , Adulto , Pronóstico , Unidades de Cuidados Intensivos , Respiración ArtificialRESUMEN
BACKGROUND: The risk-benefit relationship of immunosuppressive therapies (ISTs) for elderly patients with neuromyelitis optica spectrum disorder (NMOSD) is not well established. This study aimed to investigate the safety and efficacy of IST in elderly patients with NMOSD. METHODS: This retrospective study analysed IST efficacy and safety in 101 patients with aquaporin-4 antibody-positive NMOSD aged over 65 years, treated for at least 6 months at five Korean referral centres, focusing on relapse rates, infection events and discontinuation due to adverse outcomes. RESULTS: The mean age at disease onset was 59.8 years, and female-to-male ratio was 4:1. Concomitant comorbidities at NMOSD diagnosis were found in 87 patients (86%). The median Expanded Disability Status Scale score at the initiation of IST was 3.5. The administered ISTs included azathioprine (n=61, 60%), mycophenolate mofetil (MMF) (n=48, 48%) and rituximab (n=41, 41%). Over a median of 5.8 years of IST, 58% of patients were relapse-free. The median annualised relapse rate decreased from 0.76 to 0 (p<0.001), and 81% experienced improved or stabilised disability. Patients treated with rituximab had a higher relapse-free rate than those treated with azathioprine or MMF (p=0.022). During IST, 21 patients experienced 25 severe infection events (SIEs) over the age of 65 years, and 3 died from pneumonia. 14 patients (14%) experienced 17 adverse events that led to switching or discontinuation of IST. When comparing the incidence rates of SIEs and adverse events, no differences were observed among patients receiving azathioprine, MMF and rituximab. CONCLUSION: In elderly patients with NMOSD, IST offers potential benefits in reducing relapse rates alongside a tolerable risk of adverse events.
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BACKGROUND: Sphingolipids are signaling molecules and structural components of the axolemma and myelin sheath. Plasma sphingolipid levels may reflect disease status of neuromyelitis optica spectrum disorder (NMOSD). We aimed to examine plasma sphingolipids as disease severity biomarkers for NMOSD and compare their characteristics with those of serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP). METHODS: We measured plasma sphingolipids, sNfL, and sGFAP levels in NMOSD cases with anti-aquaporin-4-antibody. An unbiased approach, partial least square discriminant analysis (PLS-DA), was utilized to determine whether sphingolipid profiles differ according to the disease state of NMOSD (presence, moderate-to-severe disability [Expanded Disease Severity Scale, (EDSS) > 3.0], and relapses). RESULTS: We investigated 81 patients and 10 controls. PLS-DA models utilizing sphingolipids successfully differentiated patients with EDSS > 3.0, but failed to identify the presence of disease and relapses. Ceramide-C14-a significant contributor to differentiating EDSS > 3.0-positively correlated with EDSS, while its levels were independent of age and the presence of relapses. This characteristic was unique from those of sNfL and sGFAP, which were affected by age and relapses as well as EDSS. CONCLUSION: Plasma sphingolipids may be useful NMOSD biomarkers for disability with distinct characteristics compared to sNfL and sGFAP.
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Biomarcadores , Proteínas de Neurofilamentos , Neuromielitis Óptica , Esfingolípidos , Humanos , Neuromielitis Óptica/sangre , Neuromielitis Óptica/diagnóstico , Biomarcadores/sangre , Femenino , Esfingolípidos/sangre , Adulto , Masculino , Persona de Mediana Edad , Proteínas de Neurofilamentos/sangre , Proteína Ácida Fibrilar de la Glía/sangre , Índice de Severidad de la Enfermedad , Acuaporina 4/sangre , Acuaporina 4/inmunologíaRESUMEN
A reciprocal relationship between perceptual learning and functional brain changes towards perceptual learning effectiveness has been demonstrated previously; however, the underlying neural correlates remain unclear. Further, visual perceptual learning (VPL) is implicated in visual field defect (VFD) recovery following chronic stroke. We investigated resting-state functional connectivity (RSFC) in the visual cortices associated with mean total deviation (MTD) scores for VPL-induced VFD recovery in chronic stroke. Patients with VFD due to chronic ischemic stroke in the visual cortex received 24 VPL training sessions over 2 months, which is a dual discrimination task of orientation and letters. At baseline and two months later, the RSFC in the ipsilesional, interhemispheric, and contralesional visual cortices and MTD scores in the affected hemi-field were assessed. Interhemispheric visual RSFC at baseline showed the strongest correlation with MTD scores post-2-month VPL training. Notably, only the subgroup with high baseline interhemispheric visual RSFC showed significant VFD improvement following the VPL training. The interactions between the interhemispheric visual RSFC at baseline and VPL led to improvement in MTD scores and largely influenced the degree of VFD recovery. The interhemispheric visual RSFC at baseline could be a promising brain biomarker for the effectiveness of VPL-induced VFD recovery.
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Accidente Cerebrovascular , Corteza Visual , Humanos , Campos Visuales , Aprendizaje Espacial , Encéfalo , Corteza Visual/diagnóstico por imagen , Daño Encefálico Crónico , Imagen por Resonancia MagnéticaRESUMEN
Alzheimer's disease (AD) is a neurodegenerative disease accompanied by neuroimmune inflammation in the frontal cortex and hippocampus. Recently, the presence of bacteria in AD-affected brains has been documented, prompting speculation about their potential role in AD-associated neuroinflammation. However, the characterization of bacteriota in human brains affected by AD remains inconclusive. This study aimed to investigate potential associations between specific bacteria and AD pathology by examining brain tissues from AD-associated neurodegenerative regions (frontal cortex and hippocampus) and the non-AD-associated hypothalamus. Employing 16S rRNA gene sequencing, 30 postmortem brain tissue samples from four individuals with normal brain histology (N) and four AD patients were analyzed, along with three blank controls. A remarkably low biomass characterized the brain bacteriota, with their overall structures delineated primarily by brain regions rather than the presence of AD. While most analyzed parameters exhibited no significant distinction in the brain bacteriota between the N and AD groups, the unique detection of Cloacibacterium normanense in the AD-associated neurodegenerative regions stood out. Additionally, infection-associated bacteria, as opposed to periodontal pathogens, were notably enriched in AD brains. This study's findings provide valuable insights into potential link between bacterial infection and neuroinflammation in AD.
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Enfermedad de Alzheimer , Enfermedades Neurodegenerativas , Humanos , Enfermedad de Alzheimer/patología , Enfermedades Neurodegenerativas/patología , Enfermedades Neuroinflamatorias , Biomasa , ARN Ribosómico 16S/genética , Encéfalo/patología , Bacterias/genéticaRESUMEN
BACKGROUND: Air pollutant concentrations in South Korea vary greatly by region and time. To assess temporal and spatial associations of stroke subtypes with long-term air pollution effects on stroke mortality, we studied ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). METHODS: This was an observational study conducted in South Korea from 2001-2018. Concentrations of carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), and particulate matter ≤10 µm in diameter (PM10) were determined from 332 stations. Average air pollutant concentrations in each district were determined by distance-weighted linear interpolation. The nationwide stroke mortality rates in 249 districts were obtained from the Korean Statistical Information Service. Time intervals were divided into three consecutive 6-year periods: 2001-2006, 2007-2012, and 2013-2018. RESULTS: The concentrations of air pollutants gradually decreased from 2001-2018, along with decreases in IS and ICH mortality rates. However, mortality rates associated with SAH remained constant. From 2001-2006, NO2 (adjusted odds ratio [aOR]:1.13, 95% confidence interval: 1.08-1.19), SO2 (aOR: 1.10, 1.07-1.13), and PM10 (aOR: 1.12, 1.06-1.18) concentrations were associated with IS mortality, and SO2 (aOR: 1.07, 1.02-1.13) and PM10 (aOR:1.11,1.06-1.22) concentrations were associated with SAH-associated mortality. Air pollution was no longer associated with stroke mortality from 2007 onward, as the air pollution concentration continued to decline. Throughout the entire 18-year period, ICH-associated mortality was not associated with air pollution. CONCLUSIONS: Considering temporal and spatial trends, high concentrations of air pollutants were most likely to be associated with IS mortality. Our results strengthen the existing evidence of the deleterious effects of air pollution on IS mortality.
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Contaminantes Atmosféricos , Contaminación del Aire , Accidente Cerebrovascular , Humanos , Dióxido de Nitrógeno/efectos adversos , Contaminación del Aire/efectos adversos , Contaminantes Atmosféricos/efectos adversos , República de Corea/epidemiología , Accidente Cerebrovascular/diagnósticoRESUMEN
BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) stands out among CNS inflammatory demyelinating diseases (CIDDs) due to its unique disease characteristics, including severe clinical attacks with extensive lesions and its association with systemic autoimmune diseases. We aimed to investigate whether characteristics of B cell receptors (BCRs) differ between NMOSD and other CIDDs using high-throughput sequencing. METHODS: From a prospective cohort, we recruited patients with CIDDs and categorized them based on the presence and type of autoantibodies: NMOSD with anti-aquaporin-4 antibodies, myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) with anti-myelin oligodendrocyte glycoprotein antibodies, double-seronegative demyelinating disease (DSN), and healthy controls (HCs). The BCR features, including isotype class, clonality, somatic hypermutation (SHM), and the third complementarity-determining region (CDR3) length, were analyzed and compared among the different disease groups. RESULTS: Blood samples from 33 patients with CIDDs (13 NMOSD, 12 MOGAD, and 8 DSN) and 34 HCs were investigated for BCR sequencing. Patients with NMOSD tended to have more activated BCR features compare to the other disease groups. They showed a lower proportion of unswitched isotypes (IgM and IgD) and a higher proportion of switched isotypes (IgG), increased clonality of BCRs, higher rates of SHM, and shorter lengths of CDR3. Notably, advanced age was identified as a clinical factor associated with these activated BCR features, including increased levels of clonality and SHM rates in the NMOSD group. Conversely, no such clinical factors were found to be associated with activated BCR features in the other CIDD groups. CONCLUSIONS: NMOSD patients, among those with CIDDs, displayed the most pronounced B cell activation, characterized by higher levels of isotype class switching, clonality, SHM rates, and shorter CDR3 lengths. These findings suggest that B cell-mediated humoral immune responses and characteristics in NMOSD patients are distinct from those observed in the other CIDDs, including MOGAD. Age was identified as a clinical factor associated with BCR activation specifically in NMOSD, implying the significance of persistent B cell activation attributed to anti-aquaporin-4 antibodies, even in the absence of clinical relapses throughout an individual's lifetime.
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Neuromielitis Óptica , Humanos , Acuaporina 4 , Estudios Prospectivos , Glicoproteína Mielina-Oligodendrócito , Autoanticuerpos , Receptores de Antígenos de Linfocitos BRESUMEN
Background: Video head impulse tests (vHITs), assessing the vestibulo-ocular reflex (VOR), may be helpful in the differential diagnosis of acute dizziness. We aimed to investigate vHITs in patients with acute posterior circulation stroke (PCS) to examine whether these findings could exhibit significant abnormalities based on lesion locations, and to evaluate diagnostic value of vHIT in differentiating dizziness between PCS and vestibular neuritis (VN). Methods: We prospectively recruited consecutive 80 patients with acute PCS and analyzed vHIT findings according to the presence of dorsal brainstem stroke (DBS). We also compared vHIT findings between PCS patients with dizziness and a previously studied VN group (n = 29). Receiver operating characteristic (ROC) analysis was performed to assess the performance of VOR gain and its asymmetry in distinguishing dizziness between PCS and VN. Results: Patients with PCS underwent vHIT within a median of 2 days from stroke onset. Mean horizontal VOR gain was 0.97, and there was no significant difference between PCS patients with DBS (n = 15) and without (n = 65). None exhibited pathologic overt corrective saccades. When comparing the PCS group with dizziness (n = 40) to the VN group (n = 29), patients with VN demonstrated significantly lower mean VOR gains in the ipsilesional horizontal canals (1.00 vs. 0.57, p < 0.001). VOR gain and their asymmetry effectively differentiated dizziness in the PCS from VN groups, with an area under the ROC curve of 0.86 (95% CI 0.74-0.98) and 0.91 (95% CI 0.83-0.99, p < 0.001), respectively. Conclusion: Significantly abnormal vHIT results were rare in patients with acute PCS, even in the presence of DBS. Moreover, vHIT effectively differentiated dizziness between PCS and VN, highlighting its potential for aiding differential diagnosis of acute dizziness.
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The endoplasmic reticulum (ER) is selectively degraded by ER-phagy to maintain cell homeostasis. α-synuclein accumulates in the ER, causing ER stress that contributes to neurodegeneration in Parkinson's disease (PD), but the role of ER-phagy in α-synuclein modulation is largely unknown. Here, we investigated the mechanisms by which ER-phagy selectively recognizes α-synuclein for degradation in the ER. We found that ER-phagy played an important role in the degradation of α-synuclein and recovery of ER function through interaction with FAM134B, where calnexin is required for the selective FAM134B-mediated α-synuclein clearance via ER-phagy. Overexpression of α-synuclein in the ER of the substantia nigra (SN) resulted in marked loss of dopaminergic neurons and motor deficits, mimicking PD characteristics. However, enhancement of ER-phagy using FAM134B overexpression in the SN exerted neuroprotective effects on dopaminergic neurons and recovered motor performance. These data suggest that ER-phagy represents a specific ER clearance mechanism for the degradation of α-synuclein.
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Fármacos Neuroprotectores , Enfermedad de Parkinson , Humanos , alfa-Sinucleína , Retículo Endoplásmico , AutofagiaRESUMEN
BACKGROUND: There are limited data on the impact of routine use of brain magnetic resonance imaging (MRI) on the prognosis of neurologically asymptomatic patients with left-sided infective endocarditis (IE). METHODS: Among patients diagnosed with possible or definite IE in two tertiary referral centers between January 2005 and March 2019, we identified 527 left-sided IE patients without neurological symptoms or signs at the time of diagnosis. Patients who underwent brain MRI within 1 week after the IE diagnosis were classified as the routine brain imaging group (n = 216), and the rest were categorized as the control group (n = 311). All-cause mortality at 3 months, attributable mortality (defined as death directly related to IE), and fatal neurological events compared after adjustment using inverse probability of treatment weighting (IPTW). RESULTS: During a median follow-up of 57 months, the routine brain imaging group had a similar risk of 3-month all-cause mortality to the control group in the multivariate analysis (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.24-1.14) and IPTW-adjusted cohort (HR, 0.59; 95% CI, 0.25-1.42). The risks of attributable mortality and fatal neurological events were also similar between the two groups in the multivariable analysis and IPTW-adjusted cohort. In the subgroup analysis, the routine brain imaging group showed more favorable outcomes in cases of large vegetation (> 10 mm) or acute-onset microorganisms. CONCLUSIONS: Routine use of brain MRI in left-sided IE patients without neurological manifestations is not associated with improved clinical outcomes. However, routine brain imaging in appropriate clinical settings could improve clinical outcomes.
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Endocarditis Bacteriana , Endocarditis , Humanos , Endocarditis Bacteriana/diagnóstico , Endocarditis/diagnóstico por imagen , Pronóstico , Encéfalo/diagnóstico por imagen , Neuroimagen , Estudios RetrospectivosRESUMEN
Several epidemiological studies have demonstrated that genetic and environmental factors contribute to the development of allergic diseases. However, there is limited information on these factors in the Korean population. This study investigated the importance of genetic and environmental factors in allergic diseases, such as allergic rhinitis, asthma, allergic conjunctivitis, or atopic dermatitis, by comparing the disease incidence in Korean adult monozygotic and dizygotic twins. This cross-sectional study utilized data from 1296 twin pairs, including 1052 monozygotic and 244 dizygotic twins, aged over 20 years, from the Korean Genome and Epidemiology Study (2005-2014). The study utilized binomial and multinomial logistic regression models to compute odds ratios of disease concordance. The concordance rate (92%) of the presence or absence of atopic dermatitis in monozygotic twins was slightly higher than that in dizygotic twins (90.2%), which only had a borderline significance (p = 0.090). The concordance rates of other allergic diseases within monozygotic twins were lower compared to dizygotic twins (asthma, 94.3% vs. 95.1%; allergic rhinitis, 77.5% vs. 78.7%; allergic conjunctivitis, 90.6% vs. 91.8%), of which the differences were not statistically significant. Monozygotic twins had a higher proportion of cases in which both siblings had allergic diseases than dizygotic twins (asthma, 1.1% vs. 0.0%; allergic rhinitis, 6.7% vs. 3.3%; atopic dermatitis, 2.9% vs. 0.0%; allergic conjunctivitis, 1.5% vs. 0.0%), of which the differences were also not statistically significant. In conclusion, our results appear to indicate the relative importance of environmental factors over genetic factor in the development of allergic diseases in Korean adult monozygotic twins.