RESUMO
Differential diagnosis of acute loss of consciousness (LOC) is crucial due to the need for different therapeutic strategies despite similar clinical presentations among etiologies such as nonconvulsive status epilepticus, metabolic encephalopathy, and benzodiazepine intoxication. While altered functional connectivity (FC) plays a pivotal role in the pathophysiology of LOC, there has been a lack of efforts to develop differential diagnosis artificial intelligence (AI) models that feature the distinctive FC change patterns specific to each LOC cause. Three approaches were applied for extracting features for the AI models: three-dimensional FC adjacency matrices, vectorized FC values, and graph theoretical measurements. Deep learning using convolutional neural networks (CNN) and various machine learning algorithms were implemented to compare classification accuracy using electroencephalography (EEG) data with different epoch sizes. The CNN model using FC adjacency matrices achieved the highest accuracy with an AUC of 0.905, with 20-s epoch data being optimal for classifying the different LOC causes. The high accuracy of the CNN model was maintained in a prospective cohort. Key distinguishing features among the LOC causes were found in the delta and theta brain wave bands. This research advances the understanding of LOC's underlying mechanisms and shows promise for enhancing diagnosis and treatment selection. Moreover, the AI models can provide accurate LOC differentiation with a relatively small amount of EEG data in 20-s epochs, which may be clinically useful.
Assuntos
Inteligência Artificial , Eletroencefalografia , Inconsciência , Humanos , Eletroencefalografia/métodos , Inconsciência/fisiopatologia , Feminino , Diagnóstico Diferencial , Masculino , Pessoa de Meia-Idade , Adulto , Redes Neurais de Computação , Aprendizado Profundo , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Idoso , Aprendizado de MáquinaRESUMO
We aimed to identify structural and functional changes in healthy adults with catch-up sleep (CUS), we applied seed-based functional connectivity (FC) analysis using resting-state functional magnetic resonance imaging (MRI). We hypothesized that deficits in reward processing could be a fundamental mechanism underlying the motivation of taking CUS. Then, 55 healthy adults voluntarily (34 with CUS and 21 without CUS) participated in this study. Voxel-based morphometry was performed to explore region of gray matter volume (GMV) difference between CUS and non-CUS groups. Between-group comparison of FC was then carried out using resting-state functional MRI analysis seeding at the region of volume difference. Moreover, the region of volume difference and the strength of FC were correlated with scores of questionnaires for reward-seeking behavior and clinical variables. CUS group had a higher reward-seeking tendency, and increased GMV in the bilateral nucleus accumbens and right superior frontal gyrus relative to non-CUS group. FC analysis seeding at the bilateral accumbens revealed increases of FC in the bilateral medial prefrontal cortex in CUS group compared to non-CUS group. The questionnaire scores reflecting the reward-seeking tendency were correlated with the FC strength between bilateral accumbens and medial prefrontal cortex. Our results indicate that CUS is associated with reward-seeking tendency and increased GMV and FC in regions responsible for reward network. Our findings suggest that enhanced reward network could be the crucial mechanism underlying taking CUS and might be implicated in the detrimental effects of circadian misalignment.
Assuntos
Mapeamento Encefálico , Substância Cinzenta , Humanos , Adulto , Mapeamento Encefálico/métodos , Substância Cinzenta/diagnóstico por imagem , Córtex Cerebral , Recompensa , Sono , Imageamento por Ressonância Magnética/métodosRESUMO
PURPOSE: To delineate the association between otolith function and changes in mean orthostatic blood pressure (BP) and heart rate (HR) in patients with postural orthostatic tachycardia syndrome (POTS). METHODS: Forty-nine patients with POTS were prospectively recruited. We analyzed the results of ocular vestibular-evoked myogenic potentials (oVEMPs) and cervical vestibular-evoked myogenic potentials (cVEMPs), as well as head-up tilt table tests using a Finometer. The oVEMP and cVEMP responses were obtained using tapping stimuli and 110 dB tone-burst sounds, respectively. We measured maximal changes in 5-s averaged systolic BP (SBP), diastolic BP (DBP), and heart rate (HR) within 15 s and during 10 min after tilting. We compared the results with those of 20 age- and sex-matched healthy participants. RESULTS: The n1-p1 amplitude of oVEMPs was larger in patients with POTS than in healthy participants (p = 0.001), whereas the n1 latency (p = 0.280) and interaural difference (p = 0.199) did not differ between the two. The n1-p1 amplitude was a positive predictor for POTS (odds ratio 1.07, 95% confidence interval 1.01-1.13, p = 0.025). Body weight (p = 0.007) and n1-p1 amplitude of oVEMP (p = 0.019) were positive predictors for ΔSBP15s in POTS, whereas aging was a negative predictor (p = 0.005). These findings were not observed in healthy participants. CONCLUSIONS: Augmented utricular inputs may be associated with a relative predominance of sympathetic over vagal control of BP and HR, especially for an early response during orthostasis in patients with POTS. Overt sympathoexcitation due to exaggerated utricular input and lack of readaptation may be associated with the pathomechanism of POTS.
Assuntos
Síndrome da Taquicardia Postural Ortostática , Potenciais Evocados Miogênicos Vestibulares , Humanos , Síndrome da Taquicardia Postural Ortostática/diagnóstico , Potenciais Evocados Miogênicos Vestibulares/fisiologia , Frequência Cardíaca , Envelhecimento , Pressão SanguíneaRESUMO
PURPOSE: We investigated sex differences in the effect of seizures on social anxiety in persons with epilepsy. METHOD: In this cross-sectional multicenter study, social anxiety was measured using the short forms of the Social Phobia Scale (SPS-6) and Social Interaction Anxiety Scale (SIAS-6). SPS-6 scoresâ¯≥â¯9 and SIAS-6 scoresâ¯≥â¯12 were considered to indicate social phobia and social interaction anxiety, respectively. The Patient Health Questionnaire-9, Stigma Scale-Revised, and Family Adaptation-Partnership-Growth-Affection-Resolve scale were also completed. A logistic regression analysis with an interaction term was used to analyze the data. RESULTS: Out of 285 participants, a SPS-6 scoreâ¯≥â¯9 and a SIAS-6 scoreâ¯≥â¯12 were noted in 62 (21.8%) and 36 (12.6%) of participants, respectively. There was no difference in the prevalence of social anxiety between men and women. Intractable seizures and lack of seizure freedom were associated with a SPS-6 scoreâ¯≥â¯9 and a SIAS-6 scoreâ¯≥â¯12, but statistical significance was lost in the adjusted models. However, intractable seizures and lack of seizure freedom significantly interacted with sex for a SPS-6 scoreâ¯≥â¯9 (pâ¯=â¯0.018) and a SIAS-6 scoreâ¯≥â¯12 (pâ¯=â¯0.048) in both the separate and adjusted models. Specifically, intractable seizures tended to be positively associated with SPS-6 scoresâ¯≥â¯9 than non-intractable seizures in men only (odds ratioâ¯=â¯2.602, pâ¯=â¯0.068), whereas lack of seizure freedom tended to be negatively associated with SIAS-6 scoresâ¯≥â¯12 than seizure freedom in women only (odds ratioâ¯=â¯4.804, pâ¯=â¯0.053). CONCLUSION: We found significant sex differences in seizure effects on social anxiety. Intractable seizures were associated with social phobia in men, whereas lack of seizure freedom in the last year was associated with social interaction anxiety in women.
RESUMO
OBJECTIVE: Scarce data are available regarding the proportion of drugs that have provoked new-onset seizures. The aim of this study was to investigate the types of causative drugs of drug-induced new-onset seizures in a relatively large population of patients who were admitted to our epilepsy monitoring unit. METHODS: Using a hospital-based database, patients with new-onset seizures were selected and the underlying etiology of new-onset seizures was reviewed. Based on the etiologic conditions, acute symptomatic seizure was classified into 7 groups of provocation factors: drug, alcohol, encephalitis, stroke, hypoxic injury, metabolic, and unclassified. Causative drugs for new-onset seizures were further investigated. RESULTS: Altogether, 363 patients with new-onset seizures were reviewed in this study. The most common cause of new-onset seizures was epilepsy, followed by syncope, acute symptomatic seizure, and others. Drugs were found to be the most common provocation factor for acute symptomatic seizures. The most common causative drug was antihistamine, followed by stimulants, antibiotics, and other drugs. Most patients with antihistamine-induced seizures had normal renal function and were under treatment at the therapeutic dose. CONCLUSION: In our population, antihistamine accounted for the highest proportion of drug-induced seizures. Considering that antihistamines are widely used as over-the-counter drugs around the world, they should be considered a possible cause of new-onset seizures.
Assuntos
Epilepsias Parciais , Epilepsia Generalizada , Epilepsia Tônico-Clônica , Anticonvulsivantes/efeitos adversos , Carbamazepina/uso terapêutico , Epilepsias Parciais/tratamento farmacológico , Epilepsia Generalizada/tratamento farmacológico , Epilepsia Tônico-Clônica/tratamento farmacológico , Antagonistas dos Receptores Histamínicos/uso terapêutico , Humanos , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Convulsões/epidemiologiaRESUMO
PURPOSE: Obsessive-compulsive disorder (OCD) is a common but underrecognized psychiatric condition comorbid with epilepsy. We thus investigated clinical factors associated with obsessive-compulsive symptoms (OCS) in adults with epilepsy. METHODS: This was a cross-sectional multicenter study in Republic of Korea. Obsessive-compulsive symptoms were assessed using the Obsessive-Compulsive Inventory-Revised (OCI-R). Clinical factors that were assessed included age, sex, seizure-related variables, and the number and use of antiepileptic drugs (AEDs) prescribed. Data were analyzed by stepwise linear regression and adjusted according to anxiety and depressive symptoms as assessed by Hospital Anxiety Depression Scale (HADS). RESULTS: The study population comprised 221 adults with epilepsy (42.1% male, 39.7⯱â¯11.9â¯years of age). The mean OCI-R score was 18.0 (standard deviation, 12.7), and an OCI-R score of ≥21 was obtained for 40.3% of the study sample. On a stepwise linear regression analysis, epilepsy severity, temporal lobe seizures, the use of topiramate, and the use of lamotrigine were identified as independent factors associated with OCI-R score after adjusting for anxiety according to the HADS. All factors except topiramate usage were positively associated with OCS. The total explained variance was 37.3%. CONCLUSIONS: Obsessive-compulsive symptoms are common in persons with epilepsy and are associated with severe epilepsy, temporal lobe seizures, and the use of topiramate and lamotrigine. Specifically, the use of lamotrigine may aggravate OCS, whereas the use of topiramate may have beneficial effects on OCS.
Assuntos
Anticonvulsivantes/farmacologia , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Transtorno Obsessivo-Compulsivo/induzido quimicamente , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Transtorno Obsessivo-Compulsivo/epidemiologia , Adulto , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologiaRESUMO
PURPOSE: The purpose of this study was to evaluate differences in stigma, disclosure management of epilepsy, and knowledge about epilepsy between patients with epilepsy who recognized and did not recognize the new Korean term for epilepsy. METHODS: This was a cross-sectional, multicenter study. The Stigma Scale-Revised, the Disclosure Management Scale, the Patient Health Questionnaire-9, and a questionnaire assessing knowledge about epilepsy were used. The set of questionnaires had two versions, using either the old or new name for epilepsy. Multivariate logistic regression analyses were used. RESULTS: A total of 341 patients with epilepsy and 509 family members were recruited. Approximately 62% of patients felt some degree of epilepsy-related stigma. Mild stigma, severe concealment of epilepsy diagnosis, and increased knowledge about epilepsy were independently identified as factors associated with recognition of the new term in patients. Recognition of the new term was more prevalent in patients and family members with higher education, female family members, and family members having patients with younger age at seizure onset and shorter duration of epilepsy. There were no significant differences between the two types of questionnaires. About 81% of patients and 93% of family members had a positive attitude about renaming epilepsy. CONCLUSION: The use of the new Korean term for epilepsy (cerebroelectric disorder) increased knowledge about epilepsy but did not reduce stigma and concealment of epilepsy diagnosis in Korean adults with epilepsy. Higher education may be an important factor for knowing the new term in patients and family members.
Assuntos
Epilepsia , Conhecimentos, Atitudes e Prática em Saúde/etnologia , Estigma Social , Terminologia como Assunto , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia/etnologiaRESUMO
PURPOSE: Literature regarding family stigma related to epilepsy is scarce. This study investigated the prevalence of family stigma and depressive symptoms and the associated factors among the family members of patients with epilepsy. METHODS: In a cross-sectional study, Stigma Scale-Revised scoreâ¯≥â¯4 and Patient Health Questionnaire-9 scoreâ¯≥â¯10 were considered indicative of moderate-to-severe stigma and depressive symptoms, respectively. Stepwise logistic regression analyses were performed. RESULTS: Of the 482 family members, a mean age was 47.1⯱â¯9.4â¯years, and 73.4% were female. Of the patients, a mean age was 25.5⯱â¯16.7â¯years, and 45.0% were female. Idiopathic generalized epilepsy and focal epilepsy were noted in 22.4% and 65.6% of patients, respectively. Family stigma and depressive symptoms were noted in 10.0% and 11.2% of family members, respectively. Family stigma was significantly associated with high seizure frequency and being a sibling or offspring of a patient independent of their depressive symptoms. By contrast, depressive symptoms in family members were significantly associated with polytherapy, being parents of a patient, and neurological comorbidities independent of family stigma. In a subset of patients and their family, patients had higher proportion of stigma and depressive symptoms than their family. Depressive symptoms and stigma among patients were significantly correlated with those among parents, but not spouse. CONCLUSION: Family stigma is common in families with epilepsy and is closely related to depressive symptoms. Frequent seizures, polytherapy, neurological comorbidities, and the relationship to a patient may be factors that are independently associated with family stigma and depressive symptoms in family members.
Assuntos
Depressão/epidemiologia , Depressão/psicologia , Epilepsia/epidemiologia , Epilepsia/psicologia , Família/psicologia , Estigma Social , Adolescente , Adulto , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autorrelato , Adulto JovemRESUMO
OBJECTIVE: Altered thalamocortical network has been proposed to play a pivotal role in the principal pathophysiology underlying juvenile myoclonic epilepsy (JME). Recently, resting-state fMRI studies have provided converging evidence for thalamocortical dysconnectivity in patients with JME. Herein, we investigated the amplitude and spatial distribution of spontaneous low-frequency oscillations using analysis of fractional amplitude of low-frequency fluctuation (fALFF) in a large group of JME patients in comparison with controls. METHODS: Volumetric MRI and resting-state fMRI were acquired in 75 patients with JME and 62 matched controls. After preprocessing of MRI data, fALFF was computed and then Z-transformed for standardization. fALFF was compared between controls and patients, and correlation analysis between regional fALFF and clinical parameters were performed in patients. RESULTS: Compared with controls, JME patients revealed significant fALFF increases in the bilateral medial thalamus, insular cortex/inferior frontal gyrus, and cerebellum vermis (false discovery rate-corrected P < 0.05). There was no region of fALFF reduction in JME patients relative to controls. No significant correlation was observed between regional fALFF and disease duration or cumulative number of generalized tonic-clonic seizures. CONCLUSIONS: We have shown alterations of low-frequency oscillations in the thalamus, insular cortex/inferior frontal gyrus, and cerebellum in patients with JME, implicating cerebello-thalamocortical network abnormality in the pathophysiology underlying JME. Our results could further support the recent concept that JME is a network epilepsy involving specific cortical and subcortical structures, especially the cerebello-thalamocortical network.
Assuntos
Cerebelo/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Epilepsia Mioclônica Juvenil/diagnóstico por imagem , Tálamo/diagnóstico por imagem , Adolescente , Adulto , Cerebelo/fisiopatologia , Córtex Cerebral/fisiopatologia , Estudos Transversais , Feminino , Humanos , Masculino , Epilepsia Mioclônica Juvenil/fisiopatologia , Estudos Prospectivos , Tálamo/fisiopatologia , Adulto JovemRESUMO
PURPOSE: The aim of this study was to examine social anxiety in South Korean adults with epilepsy and to identify associated factors. METHOD: This was a cross-sectional, multicenter study in South Korea. Social anxiety was assessed using short forms of the Social Phobia Scale (SPS-6) and Social Interaction Anxiety Scale (SIAS-6). The SPS-6 scores ≥9 and SIAS-6 scores ≥12 were considered indicative of social phobia and social interaction anxiety, respectively. The Patient Health Questionnaire-9 (PHQ-9); Stigma Scale-Revised (SS-R); Disclosure Management Scale; Family Adaptation, Partnership, Growth, Affection, Resolve (F-APGAR) scale; and a questionnaire assessing knowledge about epilepsy were also used. RESULTS: Of a total of 219 patients with epilepsy, 21% and 11% had SPS-6 scores ≥9 and SIAS-6 scores ≥12, respectively. In logistic regression analysis, SPS-6 scores ≥9 were independently associated with SS-R scores of 4-9 (odds ratio [OR]: 8.626, 95% confidence interval [CI]: 2.515-29.587, pâ¯=â¯.001), SS-R scores 1-3 (OR: 5.496, 95% CI: 1.757-17.197, pâ¯=â¯.003), and PHQ-9 scores ≥10 (OR: 4.092, 95% CI: 1.823-9.185, pâ¯=â¯.001). In contrast, SIAS-6 scores ≥12 were related only to PHQ-9 scores ≥10 (OR: 8.740, 95% CI: 3.237-23.599, pâ¯<â¯.001). Belonging to a dysfunctional family and lack of knowledge about epilepsy tended to be associated with social phobia (pâ¯=â¯.071) and social interaction anxiety (pâ¯=â¯.090), respectively. Epilepsy-related variables were not related to social anxiety. CONCLUSION: Social anxiety is not rare in patients with epilepsy. In this study, social phobia was associated with perceived stigma and depressive symptoms, whereas social interaction anxiety was related only to depressive symptoms in patients with epilepsy.
Assuntos
Epilepsia/epidemiologia , Epilepsia/psicologia , Fobia Social/epidemiologia , Fobia Social/psicologia , Estigma Social , Adulto , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Ansiedade/psicologia , Estudos Transversais , Epilepsia/diagnóstico , Feminino , Humanos , Relações Interpessoais , Masculino , Pessoa de Meia-Idade , Fobia Social/diagnóstico , Escalas de Graduação Psiquiátrica , República da Coreia/epidemiologia , Inquéritos e QuestionáriosRESUMO
[Purpose] This study was to compare the shoulder and trunk muscle activity according to the various resistance condition during knee push-up-plus. [Subjects and Methods] Twenty healthy adults participated in this study (9 males and 11 females). The subjects performed dominant-leg-extended knee push-up-plus apply to resistance in the direction of abduction, adduction, extension and the flexion. The surface Electromyography activities of the upper trapezius, serratus anterior, homolateral external oblique and the heterolateral internal oblique were measured. The Electromyography activities of each muscle were compared using a one-way repeated analysis of variance. [Results] The Electromyography activities of serratus anterior and external oblique muscles between the resistance directions were significantly increased extension. The Electromyography activities of heterolateral internal oblique muscle between the resistance directions were significantly increased adduction. [Conclusion] To suggest use of the decision exercise tolerance orientation when muscle strengthening exercises for shoulder and trunk according to variation resistance in lower extremity during Push-up-plus.
RESUMO
BACKGROUND AND PURPOSE: We investigated clinical and radiological characteristics of ischemic stroke patients with Takotsubo-like myocardial dysfunction. METHODS: From multicenter stroke registry database, ischemic stroke patients who underwent transthoracic echocardiography were found. Among these, patients were classified if they had specific ventricular regional wall motion abnormalities discording with coronary artery distribution, such as apical (typical pattern) or nonapical ballooning (atypical pattern), considered as echocardiographic findings of Takotsubo cardiomyopathy. Patients with ischemic heart disease history, myocarditis, or pheochromocytoma were excluded. We compared patients with Takotsubo-like myocardial dysfunction with those without and further performed systematic literature review on those with Takotsubo cardiomyopathy. RESULTS: This study included 23 patients (0.42%). The mean age was 70.7±13.9 years, with predominance of women (73.9%) and typical pattern of Takotsubo-like myocardial dysfunction (91.3%). They were associated with short-term poor functional outcomes, including high mortality, neurological deterioration, and functional status at discharge, compared with those without (39.1% versus 2.4%, 47.8% versus 7.4%; and median [interquartile range], 5 [5-6] versus 3 [2-4]; all P<0.001). They had a higher inflammatory marker level and lower triglyceride level. Ischemic lesions were more commonly found in the right anterior circulation with specific dominant regions being the insula and peri-insular areas. In addition, a trend toward a remarkable mortality rate and higher prevalence of insular involvement was observed in the propensity-score matching, subgroup fulfilling the strict Takotsubo cardiomyopath criteria, and was as reported in literature review. CONCLUSION: Stroke patients with Takotsubo-like myocardial dysfunction may differ from those without in clinical outcomes, laboratory findings, and radiological features.
Assuntos
Isquemia Encefálica/diagnóstico por imagem , Sistema de Registros , Acidente Vascular Cerebral/diagnóstico por imagem , Cardiomiopatia de Takotsubo/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/epidemiologia , Comorbidade , Feminino , Hospitais/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologia , Cardiomiopatia de Takotsubo/epidemiologiaRESUMO
Alteration of basal ganglia-thalamocortical circuit has been hypothesized to play a role in the pathophysiology underlying paroxysmal kinesigenic dyskinesia (PKD). We investigated macrostructural and microstructural changes in PKD patients using structural and diffusion tensor magnetic resonance imaging (MRI) analyses. Twenty-five patients with idiopathic PKD and 25 control subjects were prospectively studied on a 3T magnetic resonance (MR) scanner. Cortical thickness analysis was used to evaluate cortical gray matter (GM) changes, and automated volumetry and shape analysis were used to assess volume changes and shape deformation of the subcortical GM structures, respectively. Tract-based spatial statistics (TBSS) was used to evaluate white matter integrity changes in a whole-brain manner, and region-of-interest (ROI) analysis of diffusion tensor metrics was performed in subcortical GM structures. Compared to controls, PKD patients exhibited a reduction in volume of bilateral thalami and regional shape deformation mainly localized to the anterior and medial aspects of bilateral thalami. TBSS revealed an increase in fractional anisotropy (FA) of bilateral thalami and right anterior thalamic radiation in patients relative to controls. ROI analysis also showed an increase in FA of bilateral thalami in patients compared to controls. We have shown evidence for thalamic abnormalities of volume reduction, regional shape deformation, and increased FA in patients with PKD. Our novel findings of concomitant macrostructural and microstructural abnormalities in the thalamus lend further support to previous observations indicating causal relationship between a preferential lesion in the thalamus and development of PKD, thus providing neuroanatomical basis for the involvement of thalamus within the basal ganglia-thalamocortical pathway in PKD.
Assuntos
Distonia/patologia , Tálamo/patologia , Adolescente , Adulto , Anisotropia , Córtex Cerebral/patologia , Imagem de Tensor de Difusão , Feminino , Lateralidade Funcional , Substância Cinzenta/patologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Tamanho do Órgão , Reconhecimento Automatizado de Padrão , Estudos Prospectivos , Adulto JovemRESUMO
Identification of new anti-apoptotic genes is important for understanding the molecular mechanisms underlying apoptosis and tumorigenesis. The present study identified a novel anti-apoptotic gene named AREL1, which encodes a HECT (homologous to E6-AP carboxyl terminus) family E3 ubiquitin ligase. AREL1 interacted with and ubiquitinated IAP antagonists such as SMAC, HtrA2, and ARTS. However, AREL1 was cytosolic and did not localize to nuclei or mitochondria. The interactions between AREL1 and the IAP antagonists were specific for apoptosis-stimulated cells, in which the IAP antagonists were released into the cytosol from mitochondria. Furthermore, the ubiquitination and degradation of SMAC, HtrA2, and ARTS were significantly enhanced in AREL1-expressing cells following apoptotic stimulation, indicating that AREL1 binds to and ubiquitinates cytosolic but not mitochondria-associated forms of IAP antagonists. Furthermore, the anti-apoptotic role of AREL1-mediated degradation of SMAC, HtrA2, and ARTS was shown by simultaneous knockdown of three IAP antagonists, which caused the inhibition of caspase-3 cleavage, XIAP degradation, and induction of apoptosis. Therefore, the present study suggests that AREL1-mediated ubiquitination and degradation of cytosolic forms of three IAP antagonists plays an important role in the regulation of apoptosis.
Assuntos
Apoptose/fisiologia , Proteínas de Transporte/metabolismo , Proteínas Inibidoras de Apoptose/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Mitocondriais/metabolismo , Proteólise , Septinas/metabolismo , Serina Endopeptidases/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação/fisiologia , Sequência de Aminoácidos , Animais , Proteínas Reguladoras de Apoptose , Proteínas de Transporte/genética , Linhagem Celular Tumoral , Serina Peptidase 2 de Requerimento de Alta Temperatura A , Humanos , Proteínas Inibidoras de Apoptose/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Camundongos , Proteínas Mitocondriais/genética , Dados de Sequência Molecular , Septinas/genética , Serina Endopeptidases/genética , Ubiquitina-Proteína Ligases/genéticaRESUMO
OBJECTIVE: Aberrant thalamocortical network has been hypothesized to play a crucial role in the fundamental pathogenesis underlying idiopathic generalized epilepsy (IGE). We aimed to investigate alterations of thalamocortical functional network in patients with IGE using thalamic seed-based functional connectivity (FC) analysis, and their relationships with frontal cognitive functions and clinical characteristics. METHODS: Forty-nine IGE patients (31 with juvenile myoclonic epilepsy, 17 with IGE with generalized tonic-clonic seizures only, one with juvenile absence epilepsy) and 42 control subjects were prospectively recruited. Voxel-based morphometry (VBM) was first performed to detect thalamic region of gray matter (GM) reduction in patients compared to controls. Between-group comparison of thalamocortical FC was then carried out using resting-state functional magnetic resonance imaging (MRI) analysis seeding at thalamic region of volume difference. In addition, thalamocortical FC was correlated with frontal cognitive performance and clinical variables. RESULTS: Neuropsychological assessment revealed that patients with IGE had poorer performance than controls on most of the frontal cognitive functions. VBM detected a reduction in GM in the anteromedial thalamus in patients relative to controls. FC analysis seeding at the anteromedial thalamus revealed a reduction of thalamocortical FC in the bilateral medial prefrontal cortex and precuneus/posterior cingulate cortex in patients with IGE compared to controls. Thalamocortical FC strength of bilateral medial prefrontal cortex correlated negatively with disease duration, but did not correlate with seizure frequency or frontal cognitive functions in patients with IGE. SIGNIFICANCE: Our results indicate that IGE is associated with decreased thalamocortical FC between anteromedial thalamus and medial prefrontal cortex and precuneus/posterior cingulate cortex. Our finding of greater reduction of medial prefrontal FC in relation to increasing disease duration suggests that thalamoprefrontal network abnormality, the proposed pathophysiologic mechanism underlying IGE, may be the consequence of the long-standing burden of the disease.
Assuntos
Epilepsia Generalizada/diagnóstico , Epilepsia Generalizada/fisiopatologia , Tálamo/patologia , Tálamo/fisiologia , Adolescente , Adulto , Estudos Transversais , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Vias Neurais/patologia , Vias Neurais/fisiologia , Estudos Prospectivos , Adulto JovemRESUMO
OBJECTIVE: We aimed to explore cortical thickness abnormalities in a homogeneous group of patients with migraine without aura and to delineate possible relationships between cortical thickness changes and clinical variables. METHODS: Fifty-six female migraine patients without aura and T2-visible white matter hyperintensities and 34 female controls were scanned on a 3T magnetic resonance imager. Cortical thickness was estimated and compared between patients and controls using a whole-brain vertex-by-vertex analysis. Correlation analysis was conducted between cortical thickness of significant clusters and clinical variables. RESULTS: Compared to controls, migraine patients had cortical thickening in left rostral middle frontal gyrus and bilateral post-central gyri. Region-of-interest analysis revealed cortical thickening of bilateral post-central gyri in migraine patients relative to controls. The average thickness of bilateral post-central gyri positively correlated with disease duration as well as estimated lifetime headache frequency. CONCLUSIONS: We have provided evidence for interictal cortical abnormalities of thickened prefrontal cortex and somatosensory cortex in female migraine patients without aura. Our findings of greater thickening of the somatosensory cortex in relation to increasing disease duration and increasing headache frequency suggest that repeated migraine attacks over time may lead to structural changes of the somatosensory cortex through increased noxious afferent input within the trigemino-thalamo-cortical pathway in migraine.
Assuntos
Enxaqueca sem Aura/patologia , Córtex Somatossensorial/patologia , Adolescente , Adulto , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Adulto JovemRESUMO
Determining the laterality of the seizure onset zone is challenging in frontal lobe epilepsy (FLE) due to the rapid propagation of epileptic discharges to the contralateral hemisphere. There is hemispheric lateralization of autonomic control, and heart rate is modulated by interactions between the sympathetic and parasympathetic nervous systems. Based on this notion, the laterality of seizure foci in FLE might be determined using heart rate variability (HRV) parameters. We explored preictal markers for differentiating the laterality of seizure foci in FLE using HRV parameters. Twelve patients with FLE (6 right FLE and 6 left FLE) were included in the analyzes. A total of 551 (460 left FLE and 91 right FLE) 1-min epoch electrocardiography data were used for HRV analysis. We found that most HRV parameters differed between the left and right FLE groups. Among the machine learning algorithms applied in this study, the light gradient boosting machine was the most accurate, with an AUC value of 0.983 and a classification accuracy of 0.961. Our findings suggest that HRV parameter-based laterality determination models can be convenient and effective tools in clinical settings. Considering that heart rate can be easily measured in real time with a wearable device, our proposed method can be applied to a closed-loop device as a real-time monitoring tool for determining the side of stimulation.
RESUMO
Alzheimer's disease (AD) is a progressive disease leading to cognitive decline, and to prevent it, researchers seek to diagnose mild cognitive impairment (MCI) early. Particularly, non-amnestic MCI (naMCI) is often mistaken for normal aging as the representative symptom of AD, memory decline, is absent. Subjective cognitive decline (SCD), an intermediate step between normal aging and MCI, is crucial for prediction or early detection of MCI, which determines the presence of AD spectrum pathology. We developed a computer-based cognitive task to classify the presence or absence of AD pathology and stage within the AD spectrum, and attempted to perform multi-stage classification through electroencephalography (EEG) during resting and memory encoding state. The resting and memory-encoding states of 58 patients (20 with SCD, 10 with naMCI, 18 with aMCI, and 10 with AD) were measured and classified into four groups. We extracted features that could reflect the phase, spectral, and temporal characteristics of the resting and memory-encoding states. For the classification, we compared nine machine learning models and three deep learning models using Leave-one-subject-out strategy. Significant correlations were found between the existing neurophysiological test scores and performance of our computer-based cognitive task for all cognitive domains. In all models used, the memory-encoding states realized a higher classification performance than resting states. The best model for the 4-class classification was cKNN. The highest accuracy using resting state data was 67.24%, while it was 93.10% using memory encoding state data. This study involving participants with SCD, naMCI, aMCI, and AD focused on early Alzheimer's diagnosis. The research used EEG data during resting and memory encoding states to classify these groups, demonstrating the significance of cognitive process-related brain waves for diagnosis. The computer-based cognitive task introduced in the study offers a time-efficient alternative to traditional neuropsychological tests, showing a strong correlation with their results and serving as a valuable tool to assess cognitive impairment with reduced bias.
Assuntos
Doença de Alzheimer , Ondas Encefálicas , Humanos , Doença de Alzheimer/diagnóstico , Eletroencefalografia , Computadores , Testes NeuropsicológicosRESUMO
Neurological disorders such as Parkinson's disease (PD) often adversely affect the vascular system, leading to alterations in blood flow patterns. Functional near-infrared spectroscopy (fNIRS) is used to monitor hemodynamic changes via signal measurement. This study investigated the potential of using resting-state fNIRS data through a convolutional neural network (CNN) to evaluate PD with orthostatic hypotension. The CNN demonstrated significant efficacy in analyzing fNIRS data, and it outperformed the other machine learning methods. The results indicate that judicious input data selection can enhance accuracy by over 85%, while including the correlation matrix as an input further improves the accuracy to more than 90%. This study underscores the promising role of CNN-based fNIRS data analysis in the diagnosis and management of the PD. This approach enhances diagnostic accuracy, particularly in resting-state conditions, and can reduce the discomfort and risks associated with current diagnostic methods, such as the head-up tilt test.
Assuntos
Hipotensão Ortostática , Redes Neurais de Computação , Doença de Parkinson , Espectroscopia de Luz Próxima ao Infravermelho , Humanos , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/fisiopatologia , Hipotensão Ortostática/fisiopatologia , Hipotensão Ortostática/diagnóstico por imagem , Masculino , Feminino , Descanso , Idoso , Pessoa de Meia-IdadeRESUMO
PURPOSE: It has been reported that restless legs syndrome (RLS) might be associated with multiple psychosomatic symptoms. We aimed to identify which psychosomatic symptom is the most related in RLS patients compared to healthy controls. We also attempted to determine the relation between psychosomatic comorbidity and RLS severity regardless of sleep-related symptoms. METHODS: One hundred two newly diagnosed patients with RLS and 37 healthy control subjects participated in the present study. The RLS patients were categorized as mild and severe based on the International RLS Study Group rating scale. Data on demographics were collected. All participants completed the Pittsburgh Sleep Quality Index, Athens Insomnia Scale, and Epworth Sleepiness Scale as sleep-related questionnaires. All participants completed the Symptom Checklist-90-Revision (SCL-90-R). RESULTS: RLS patients were found to have pervasive comorbid psychosomatic symptoms. Somatization was found to be the most significant contributing factor (OR 1.145, 95 % CI 1.061-1.234, p < 0.001) for psychosomatic comorbidity in RLS. Severe RLS patients were found to have poorer sleep quality than mild RLS patients. Furthermore, severe RLS patients had higher scores for most psychosomatic symptom domains in SCL-90-R. Anxiety was found to be the most independent contributing factor for psychosomatic comorbidity according to RLS severity (OR 1.145, 95 % CI 1.043-1.257, p = 0.005). CONCLUSIONS: Our study demonstrates that comorbid psychosomatic distress is considerable in patients with RLS. Furthermore, most psychosomatic comorbidity is increased with the RLS severity in association with poorer sleep quality.