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1.
Epilepsy Behav ; 145: 109291, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37336136

RESUMO

OBJECTIVE: To assess the effectiveness and tolerability of perampanel monotherapy following conversion from adjunctive therapy. METHODS: This was a multicenter, retrospective, non-interventional study of Korean patients aged ≥12 years with focal-onset seizures (FOS) with or without focal to bilateral tonic-clonic seizures. Data were extracted from electronic medical records of perampanel-treated patients from 1 February 2016 to 31 October 2020. Kaplan-Meier estimated retention rates, effectiveness, and safety were recorded. RESULTS: Subjects (n = 66, mean age 46.2 years) were mostly male (68.2%) with focal to bilateral tonic-clonic seizure (71.2%). Mean duration of illness was 86.3 months. Retention rates after conversion to perampanel monotherapy at 3, 6, and 12 months (primary outcome) were 96.0%, 96.0%, and 75.6%, respectively. Overall retention rates in patients receiving perampanel as adjunctive or monotherapy at 3, 6, 12, 18, and 24 months after perampanel add-on were 100%, 98.3%, 95.9%, 92.6%, and 92.6%, respectively. Mean retention duration was 41.2 months (overall perampanel administration) and 21.4 months (monotherapy). Mean seizure frequency/28 days in the Full Analysis Set (n = 61) was comparable for adjunctive and monotherapy (0.2 ± 0.79 vs 0.2 ± 0.64; change between adjunctive and monotherapy periods: 0.0 ± 0.59; p = 0.498). Perampanel was well tolerated and no new safety signals were identified. Dizziness (4.6%), only reported during adjunctive therapy, was the most common treatment-emergent adverse event. CONCLUSIONS: Conversion to perampanel monotherapy from adjunctive therapy showed promising results in subjects with FOS with/without focal to bilateral tonic-clonic seizures; further studies in a larger population are needed to confirm these encouraging data.


Assuntos
Anticonvulsivantes , Convulsões , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Anticonvulsivantes/efeitos adversos , Resultado do Tratamento , Convulsões/epidemiologia , Piridonas/efeitos adversos , Quimioterapia Combinada , República da Coreia
2.
Epilepsy Behav ; 112: 107446, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32919205

RESUMO

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.


Assuntos
Epilepsia , Estigma Social , Adulto , Estudos Transversais , Emoções , Relações Familiares , Humanos
3.
J Korean Med Sci ; 35(24): e207, 2020 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-32567259

RESUMO

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a potentially life-threatening but reversible autoimmune disorder characterized by psychiatric symptoms, cognitive dysfunction, speech dysfunction, seizures, movement disorder, decreased level of consciousness, and autonomic dysfunction or central hypoventilation. It occurs predominantly in young women and approximately half of them have underlying tumors, mainly ovarian teratoma. A 24-year old woman was admitted because of fever, headache, abnormal movement and decreased mental status. Five cycles of plasmapheresis improved her neurological and mental status. Anti-NMDAR antibodies in her CSF and serum were positive, and computed tomography revealed a 1-cm sized mass suggestive of mature cystic teratoma arising from the right ovary. We promptly performed laparoscopic right ovarian cystectomy. She was discharged after 2 weeks with mild memory deficit. Prompt removal of ovarian teratoma and multidisciplinary care are particularly important for good outcome.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Neoplasias Ovarianas/diagnóstico , Teratoma/diagnóstico , Abdome/diagnóstico por imagem , Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Encefalite Antirreceptor de N-Metil-D-Aspartato/patologia , Feminino , Humanos , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/patologia , Pelve/diagnóstico por imagem , Plasmaferese , Teratoma/complicações , Teratoma/patologia , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto Jovem
4.
Crit Care ; 20: 25, 2016 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-26812954

RESUMO

BACKGROUND: Two clinical scoring systems, the status epilepticus severity score (STESS) and the epidemiology-based mortality score in status epilepticus (EMSE), are used to predict mortality in patients with status epilepticus (SE). The aim of this study was to compare the outcome-prediction function of the two scoring systems regarding in-hospital mortality using a multicenter large cohort of adult patients with SE. Moreover, we studied the potential role of these two scoring systems in predicting the functional outcome in patients with SE. METHODS: The SE cohort consisted of patients from the epilepsy centers of eight academic tertiary medical centers in South Korea. The clinical and electroencephalography data for all adult patients with SE from January 2013 to December 2014 were derived from a prospective SE database. The primary outcome variable was defined as in-hospital death. The secondary outcome variable was defined as a poor functional outcome, i.e., a score of 1-3 on the Glasgow Outcome Scale, at discharge. RESULTS: Among the 120 non-hypoxic patients with SE recruited into the study, 16 (13.3%) died in the hospital and 64 (53.3%) were discharged with a poor functional outcome. The receiver-operating characteristic (ROC) curve for prediction of in-hospital death based on the STESS had an area under the curve of 0.673 with an optimal cutoff value for discrimination (best match for both sensitivity (0.56) and specificity (0.70)) that was ≥ 4 points. The two combinations of elements of the EMSE system (EMSE-ALDEg and EMSE-ECLEg) predicted not only in-hospital mortality with the best match for sensitivity (more than 0.6) and specificity (more than 0.6), but also a poor functional outcome with the best match for both sensitivity (>0.7) and specificity (>0.6). STESS did not predict a poor functional outcome (area under the ROC, 0.581; P = 0.23). CONCLUSION: Although the EMSE is a clinical scoring system that focuses on individual mortality, we did not find differences between the EMSE and STESS in the prediction of in-hospital death. The EMSE was useful in predicting poor functional outcome, as it was significantly better than STESS.


Assuntos
Avaliação de Resultados da Assistência ao Paciente , Valor Preditivo dos Testes , Estado Epiléptico/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Escala de Resultado de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , República da Coreia
5.
Am J Emerg Med ; 33(5): 701-4, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25745798

RESUMO

BACKGROUND: Delirium tremens (DT) is the severest form of alcohol withdrawal syndrome, frequently after alcohol withdrawal seizures. Delirium tremens occurs in a small proportion of patients with alcohol withdrawal seizures; nevertheless, early identification of high-risk patients is important for intensive preventive management of unexpected episodes due to agitation and its associated increased mortality. However, there are limited studies on clinical predictors of the development of DT in patients with alcohol withdrawal seizures. METHODS: Patients who visited the emergency department with acute seizures were included in the study when alcohol withdrawal was the only or the strongest precipitating factor for seizures. All patients were carefully observed for at least 48 hours in the intensive care unit after the initial assessment to closely monitor vital signs and development of DT. Clinical and laboratory findings were analyzed for predicting the development of DT. RESULTS: Of the 97 patients (82 males; mean age, 48.6 ± 13.3 years) with alcohol withdrawal seizures, 34 (35.1%) developed DT. Low platelet count, high blood level of homocysteine, and low blood level of pyridoxine were associated with the subsequent development of DT. Low platelet count and high blood level of homocysteine were independent risk factors with high diagnostic sensitivity and specificity for the development of DT. CONCLUSIONS: The study indicated that some easily determined parameters are potential clinical predictors for the development of DT in patients with alcohol withdrawal seizures. These findings would be helpful in clinical identification and management patients at high risk for DT.


Assuntos
Delirium por Abstinência Alcoólica/diagnóstico , Convulsões por Abstinência de Álcool/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Delirium por Abstinência Alcoólica/sangue , Biomarcadores/sangue , Serviço Hospitalar de Emergência , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco
6.
Sci Rep ; 14(1): 7228, 2024 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-38538679

RESUMO

Loss of myelin in the brain may lead to cognitive decline in Alzheimer's disease (AD). The ratio of T1 weighted/T2 weighted (T1w/T2w) on magnetic resonance imaging has been used as a proxy for myelin content in the brain. Using this approach, we investigated the correlation between the white matter (WM) T1w/T2w ratio and both cognitive scores and disease progression in AD. A total of 93 participants who were cognitively unimpaired or diagnosed with mild cognitive impairment or AD dementia were recruited between March 2021 and November 2022. All participants were assessed using neuropsychological tests, and a subset of the participants was assessed every 1 year to monitor disease progression. We observed significant positive associations between the WM T1w/T2w ratio and executive function within the fornix, sagittal stratum, anterior internal capsule, and body of the corpus callosum (False discovery rate [FDR]-corrected P-value < 0.05). There was a marginal interaction between the WM T1w/T2w ratio of the left anterior internal capsule and the longitudinal change in sum of boxes of the Clinical Dementia Rating Scale (FDR-corrected P-value = 0.05). The present study demonstrated that the WM T1w/T2w ratio was associated with executive function and disease progression, suggesting that it may be a novel neuroimaging marker for AD.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Substância Branca , Humanos , Substância Branca/diagnóstico por imagem , Doença de Alzheimer/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Cognição , Disfunção Cognitiva/diagnóstico por imagem , Bainha de Mielina , Progressão da Doença
7.
Encephalitis ; 4(2): 35-39, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38589019

RESUMO

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an autoimmune disorder with diverse clinical manifestations including myelitis, meningitis, encephalitis, and optic neuritis. MOGAD rarely presents with unilateral cerebral cortical encephalitis (CCE), rendering the diagnosis difficult in these cases. Furthermore, MOGAD is frequently accompanied by other autoimmune diseases such as thyroid disease or inflammatory bowel disease. Herein, we report a case of unilateral CCE with positive anti-myelin oligodendrocyte glycoprotein (MOG) antibodies. In addition, our patient presented with systemic symptoms as well as neurologic symptoms and was finally diagnosed with ulcerative colitis (UC). A 60-year-old female was admitted to the hospital with an acute onset of headache and fever. Neurological examination revealed left-sided homonymous hemianopsia with intermittent visual hallucinations as flickering red-circular spots in the left visual field. Brain magnetic resonance imaging showed focal hyperintensities and enhancement in the right temporo-parieto-occipital cortex. Electroencephalography indicated a focal seizure in the right occipital cortex. After the administration of an antiepileptic drug, the patient showed clinical and radiological improvements. She tested positive for serum anti-MOG antibodies and was diagnosed with anti-MOG-associated unilateral CCE. However, the gastrointestinal symptoms persisted, thus, a sigmoidoscopy was performed. The patient was diagnosed with comorbid UC. Steroids were administered to treat the UC and the gastrointestinal symptoms improved. To the best of our knowledge, this is the first case of MOGAD presenting as a unilateral CCE in Korea. This case highlights the clinical phenotypes of MOGAD and the need to assess comorbid autoimmune diseases in patients with MOGAD.

8.
J Ethnopharmacol ; 319(Pt 3): 117359, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-37924999

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Woohwangchungsimwon (WCW) is a traditional medicine used in East Asian countries to treat central nervous system disorders. Reported pharmacological properties include antioxidant effects, enhanced learning and memory, and protection against ischemic neuronal cell death, supporting its use in treating neurodegenerative diseases like Alzheimer's disease (AD). AIM OF THE STUDY: The study aims to assess the effects of co-treatment with WCW and donepezil on cognitive functions and serum metabolic profiles in a scopolamine-induced AD model. MATERIALS AND METHODS: Cell viability and reactive oxygen species (ROS) levels were measured in amyloid ß-peptide25-35 (Aß25-35)-induced SH-SY5Y cells. An AD model was established in ICR mice by intraperitoneal scopolamine administration. Animals underwent the step-through passive avoidance test (PAT) and Morris water maze (MWM) test. Hippocampal tissues were collected to examine specific protein expression. Serum metabolic profiles were analyzed using nuclear magnetic resonance (NMR) spectroscopy. RESULTS: Co-treatment with WCW and donepezil increased cell viability and reduced ROS production in Aß25-35-induced SH-SY5Y cells compared to that with donepezil treatment alone. Co-treatment improved cognitive functions and was comparable to donepezil treatment alone in the PAT and MWM tests. Pathways related to tyrosine, phenylalanine, and tryptophan biosynthesis, phenylalanine metabolism, and cysteine and methionine metabolism were altered by co-treatment. Levels of tyrosine and methionine, major serum metabolites in these pathways, were significantly reduced after co-treatment. CONCLUSIONS: Co-treatment with WCW and donepezil shows promise as a therapeutic strategy for AD and is comparable to donepezil alone in improving cognitive function. Reduced tyrosine and methionine levels after co-treatment may enhance cognitive function by mitigating hypertyrosinemia and hyperhomocysteinemia, known risk factors for AD. The serum metabolic profiles obtained in this study can serve as a foundation for developing other bioactive compounds using a scopolamine-induced mouse model.


Assuntos
Doença de Alzheimer , Neuroblastoma , Humanos , Camundongos , Animais , Camundongos Endogâmicos ICR , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/tratamento farmacológico , Donepezila , Peptídeos beta-Amiloides , Espécies Reativas de Oxigênio , Cognição , Metaboloma , Metionina , Fenilalanina , Tirosina , Derivados da Escopolamina
9.
Encephalitis ; 3(4): 109-113, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37621190

RESUMO

The global severe acute respiratory syndrome coronavirus 2 pandemic contributed to the development of a large variety of vaccines, of which postvaccinal hyperacute encephalopathy is a very rare complication. Despite its rarity, if diagnosed properly, appropriate treatment can be rapidly applied. A healthy 53-year-old woman was admitted for a seizure on the day she received the second dose of the BNT 162b2 nCoV-19 vaccine. She subsequently developed irritability, which gradually worsened over several days. Cerebrospinal fluid analysis revealed mild pleocytosis and normal protein levels. Brain magnetic resonance imaging (MRI) revealed diffuse sulcal hyperintensity on the entire brain surface on fluid-attenuated inversion recovery images with meningeal enhancement. The patient was diagnosed with hyperacute postvaccinal encephalopathy and received immunosuppressive therapy with corticosteroids and therapeutic plasmapheresis. Fortunately, the patient responded to therapy, achieving almost complete recovery from the neurological symptoms, with only mild memory impairment remaining after 3 weeks. Based on the clinical presentation, electroencephalogram findings, and MRI, our patient developed hyperacute encephalopathy within 24 hours of vaccine administration, which we surmised from the temporal course of symptoms and brain imaging findings. Further studies are required to elucidate the pathogenesis of coronavirus disease 2019 vaccination-related encephalopathy.

10.
Dement Neurocogn Disord ; 22(4): 148-157, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38025407

RESUMO

Background and Purpose: Episodic memory is a system that receives and stores information about temporally dated episodes and their interrelations. Our study aimed to investigate the relevance of episodic memory to time perception, with a specific focus on simultaneity/order judgment. Methods: Experiment 1 employed the simultaneity judgment task to discern differences in time perception between patients with mild cognitive impairment or dementia, and age-matched normals. A mathematical analysis capable of estimating subjects' time processing was utilized to identify the sensory and decisional components of temporal order and simultaneity judgment. Experiment 2 examined how differences in temporal perception relate to performance in temporal order memory, in which time delays play a critical role. Results: The temporal decision windows for both temporal order and simultaneity judgments exhibited marginal differences between patients with episodic memory impairment, and their healthy counterparts (p = 0.15, t(22) = 1.34). These temporal decision windows may be linked to the temporal separation of events in episodic memory (Pearson's ρ = -0.53, p = 0.05). Conclusions: Based on our findings, the frequency of visual events accumulated and encoded in the working memory system in the patients' and normal group appears to be approximately (5.7 and 11.2) Hz, respectively. According to the internal clock model, a lower frequency of event pulses tends to result in underestimation of event duration, which phenomenon might be linked to the observed time distortions in patients with dementia.

11.
Healthcare (Basel) ; 11(14)2023 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-37510478

RESUMO

Behavioral and psychological symptoms of dementia are a major factor in the burden of care and medical expenses. Conventional pharmacological treatments do not exert a distinct effect on the benefits versus the risks. The herbal medicine woohwangchungsimwon is frequently prescribed for neuropsychiatric disorders. An effect of woohwangchungsimwon on behavioral and psychological symptoms of dementia has been previously reported; however, no clinical studies have been conducted. We aim to evaluate the efficacy and safety of woohwangchungsimwon combined with donepezil for alleviating these symptoms in probable Alzheimer's disease. In this randomized, assessor-blinded, parallel-group clinical trial, 74 participants with probable Alzheimer's disease will be divided via block randomization into a woohwangchungsimwon + donepezil combination group (n = 37) or a donepezil single group (n = 37). Participants will include patients under donepezil treatment for at least a month. We will perform the study for 24 weeks. The Neuro-Psychiatric Inventory subscale scores will be the primary outcome. Secondary outcomes will include cognitive function, dementia severity, physical function, quality of life, depression, anxiety, and insomnia. For safety evaluation, we will assess adverse reactions, measure vital signs, and conduct laboratory tests. This is the first trial aiming to confirm the efficacy and safety of woohwangchungsimwon combined with donepezil for alleviating behavioral and psychological symptoms of dementia. Its findings could provide a basis for their co-administration to control these symptoms in probable Alzheimer's disease.

12.
J Korean Soc Radiol ; 83(4): 945-950, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36238909

RESUMO

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a common autoimmune encephalitis that is noted to be a severe but treatable disease entity. Patients with anti-NMDAR encephalitis often develop psychotic symptoms, including delusions, hallucinations, and paranoia, as well as memory impairment and persistent loss of attention. However, MRI findings in such patients show no abnormalities in most cases. Although typical brain abnormality features, known as T2 hyperintensities, involve the brain parenchyma and contrast enhancement at the cerebral cortex or overlying meninges, isolated leptomeningeal enhancement has been rarely reported in anti-NMDAR encephalitis. Herein, we report a patient with anti-NMDAR encephalitis who presented with isolated leptomeningeal enhancement, additionally showing the diagnostic value of contrast-enhanced fluid-attenuated inversion recovery imaging.

13.
Medicine (Baltimore) ; 101(38): e30301, 2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36197176

RESUMO

Despite the urgent need to control dementia, an effective treatment has yet to be developed. Along with the Korean government's policy of cooperation between conventional medicine (CM) and Korean medicine (KM), integrative medical services for dementia patients are being provided. This study aimed to compare the integrative medical clinic (IMC) for dementia used by Dongguk University Hospitals (DUH) with other service models and to review the characteristics and treatment outcomes of patients who had visited DUH over the past 5 years. Patients' electronic medical records from May 2015 to June 2020 were searched and their data were analyzed to evaluate the IMC's service model. Patient demographic and clinical characteristics, diagnostic tests, and treatment patterns for CM and KM were collected. The proportion of patients who did not show worsening cognitive function was described in detail. A strength of the DUH integrative medicine clinic is its ability to manage both KM and CM patients in the same space at the same time. Among the 82 patients who visited the clinic during our study period, 56 remained for data analysis after we excluded patients who met the exclusion criteria; nineteen patients had diagnoses of mild cognitive impairment. Among collaboration patterns, the first visit to the IMC had the highest proportion (55.4%). Among diagnosed tests in CM, laboratory tests and neuropsychological tests were used the most. In KM, a heart rate variability test was frequently used. The most common CM treatment prescribed was anticonvulsants, with 22 patients (39.2%) receiving donepezil, whereas the most frequent KM treatments were acupuncture (82.1%) and herbal medicine (78.6%). Twelve patients were followed up with the Mini-Mental State Examination, and 8 demonstrated either no worsening or improved cognition (baseline Mini-Mental State Examination range: 21-26). All 8 patients had mild cognitive impairment including 6 with amnestic, multidomain impairment. This study searched for a way to improve cognitive dysfunction and dementia using an integrative approach, and it shows promising results for mild cognitive impairment. However, more precisely designed follow-up studies are needed to address the present work's limitations of a retrospective study design and a small sample size.


Assuntos
Disfunção Cognitiva , Demência , Medicina Integrativa , Anticonvulsivantes , Cognição , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/terapia , Demência/complicações , Demência/diagnóstico , Demência/terapia , Donepezila/uso terapêutico , Humanos , Testes Neuropsicológicos , Estudos Retrospectivos
14.
Curr Alzheimer Res ; 19(3): 246-263, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35422218

RESUMO

BACKGROUND: Alzheimer's disease (AD) is a lethal, progressive neurodegenerative disorder that has been linked to a deficiency of the neurotransmitter acetylcholine. Currently, many acetylcholinesterase inhibitors, such as donepezil, are widely used for the treatment of AD. On the other hand, the efficacy of long-term donepezil use is limited. SIP3, a mixture of three herbal extracts from Santalum album, Illicium verum, and Polygala tenuifolia, is a new formula derived from traditional Korean herbal medicine. OBJECTIVE: We assessed the synergistic effect of SIP3 and donepezil co-treatment on symptoms of AD using APP/PS1 transgenic mice. METHODS: In this study, a Drosophila AD model and SH-SY5Y clles were used to assess the toxicity of SIP3, and APPswe/PS1dE9 (APP/PS1) transgenic mice were used to evaluate the cognitive-behavioral and depression-like behavior effect of SIP3 and donepezil co-treatment on symptoms of AD. The cerebral cortex or hippocampus transcriptomes were analyzed by RNA sequencing and miRNA to investigate the molecular and cellular mechanisms underlying the positive effects of SIP3 on AD. RESULTS: In the passive avoidance test (PAT) and Morris water maze (MWM) test, the combination of SIP3 and donepezil improved the learning capabilities and memory of APP/PS1 mice in the mid-stage of AD compared to the group treated with donepezil only. In addition, co-administration of SIP3 and donepezil effectively reduced the depression-like behavior in the forced swimming and tail suspension tests. Furthermore, RNA sequencing of the cerebral cortex transcriptome and miRNA of the hippocampus showed that the gene expression profiles after a low dose SIP3 co-treatment were more similar to those of the normal phenotype mice than those obtained after the donepezil treatment alone. The Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, showed that differentially expressed genes were involved in the locomotor behavior and neuroactive ligand-receptor interactions. These results suggest that a co-treatment of low dose SIP3 and donepezil improves impaired learning, memory, and depression in the mid-stage of AD in mice. CONCLUSION: Co-treatment of low dose SIP3 and donepezil improves impaired learning, memory, and depression in the mid-stage of AD in mice.


Assuntos
Doença de Alzheimer , MicroRNAs , Neuroblastoma , Acetilcolinesterase/metabolismo , Doença de Alzheimer/complicações , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Depressão , Modelos Animais de Doenças , Donepezila/farmacologia , Medicina Herbária , Hipocampo/metabolismo , Humanos , Aprendizagem em Labirinto , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos
15.
Epilepsy Behav ; 20(4): 623-32, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21273134

RESUMO

Chronic and progressive brain injury, as seen in epilepsy, may alter brain networks that underlie cognitive functions. To evaluate the effect of epilepsy on language functions we investigated the neuroanatomical basis of semantic processing in patients with left (LHE) or right (RHE) hemispheric onset epilepsy using semantic decision fMRI paradigm and group independent component analysis (ICA); we then compared the results of our investigations with language networks in healthy subjects examined with the same language task (Kim K, Karunanayaka P, Privitera M, Holland S, Szaflarski J. Semantic association investigated with fMRI and independent component analysis. In press). Group ICA is a data-driven technique capable of revealing the functional organization of the human brain based on fMRI data. In addition to providing functional connectivity information, ICA can also provide information about the temporal dynamics of underlying networks subserving specific cognitive functions. In this study, we implemented two complementary analyses to investigate group differences in underlying network dynamics based on associated independent component (IC) time courses (a priori defined criterion or a posteriori identified maximum likelihood descriptor). We detected several differences between healthy controls and patients with epilepsy not previously observed with standard fMRI analysis methods. Our analyses confirmed the presence of different effects of LHE or RHE on the behavior of the language network. In particular, a major difference was noted in the nodes subserving verbal encoding and retrieval in the bilateral medial temporal regions. These effects were dependent on the side of the epilepsy onset; that is, effects were different with left or right hemispheric epilepsy. These findings may explain the differences in verbal and nonverbal memory abilities between patients with left and those with right hemispheric epilepsy. Further, although the effects on other nodes of the network were more subtle, several deviations from normal network function were observed in patients with LHE (e.g., alterations in the functions of the primarily left frontotemporal network module) or in patients with RHE (e.g., differences in the medial retrosplenial module responsible for mental imagery or in the anterior cingulate module subserving attention control). These findings not only highlight the negative effects of epilepsy on the main left hemispheric language network nodes in patients with LHE, but also document the effects of epilepsy on other language network nodes whether exerted by LHE or RHE. Further, these results document the advantages of using group ICA for investigating the effects of disease state (e.g., epilepsy) on the network subserving cognitive processing and provide an interesting avenue for further exploration.


Assuntos
Encéfalo/irrigação sanguínea , Tomada de Decisões/fisiologia , Epilepsia/fisiopatologia , Lateralidade Funcional/fisiologia , Imageamento por Ressonância Magnética , Semântica , Adulto , Encéfalo/fisiopatologia , Mapeamento Encefálico , Processamento Eletrônico de Dados/métodos , Epilepsia/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Testes Neuropsicológicos
16.
Epilepsy Behav ; 20(4): 613-22, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21296027

RESUMO

Semantic association, an essential element of human language, enables discourse and inference. Neuroimaging studies have revealed localization and lateralization of semantic circuitry, making substantial contributions to cognitive neuroscience. However, because of methodological limitations, these investigations have only identified individual functional components rather than capturing the behavior of the entire network. To overcome these limitations, we have implemented group independent component analysis (ICA) to investigate the cognitive modules used by healthy adults performing the fMRI semantic decision task. When compared with the results of a standard general linear modeling (GLM) analysis, ICA detected several additional brain regions subserving semantic decision. Eight task-related group ICA maps were identified, including left inferior frontal gyrus (BA44/45), middle posterior temporal gyrus (BA39/22), angular gyrus/inferior parietal lobule (BA39/40), posterior cingulate (BA30), bilateral lingual gyrus (BA18/23), inferior frontal gyrus (L>R, BA47), hippocampus with parahippocampal gyrus (L>R, BA35/36), and anterior cingulate (BA32/24). Although most of the components were represented bilaterally, we found a single, highly left-lateralized component that included the inferior frontal gyrus and the medial and superior temporal gyri, the angular and supramarginal gyri, and the inferior parietal cortex. The presence of these spatially independent ICA components implies functional connectivity and can be equated with their modularity. These results are analyzed and presented in the framework of a biologically plausible theoretical model in preparation for similar analyses in patients with right- or left-hemispheric epilepsies.


Assuntos
Mapeamento Encefálico , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/fisiologia , Imageamento por Ressonância Magnética , Semântica , Adulto , Feminino , Lateralidade Funcional/fisiologia , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Oxigênio/sangue , Estatística como Assunto , Fatores de Tempo , Adulto Jovem
17.
Epileptic Disord ; 13(4): 368-74, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22258040

RESUMO

Electrocortical mapping (ECM) is recognised as an established method for localisation of eloquent cortex in patients undergoing resective surgery for epilepsy management. Functional MRI (fMRI) has been utilised for language and other cortical function localisation. We describe language localisation in two patients using both ECM and fMRI. Co-registration of fMRI and ECM revealed that although two fMRI tasks localised multiple language areas, the verb generation task had an advantage over the semantic decision/tone decision task in that there was a clear overlap between the language areas identified by the verb generation task and ECM. In addition to the language areas detected by ECM, fMRI showed other language-related areas that may be important for post-operative language outcome. Therefore, fMRI may provide additional and complementary information to ECM in presurgical evaluation of patients with epilepsy. The correlation between fMRI and ECM may depend on the language testing methods utilised during the procedures.


Assuntos
Eletroencefalografia , Epilepsia/patologia , Epilepsia/psicologia , Idioma , Imageamento por Ressonância Magnética , Neocórtex/patologia , Adulto , Mapeamento Encefálico , Tomada de Decisões , Epilepsia/cirurgia , Epilepsia Parcial Complexa/patologia , Epilepsia Parcial Complexa/psicologia , Epilepsia Parcial Complexa/cirurgia , Feminino , Humanos , Pressão Intracraniana/fisiologia , Testes de Linguagem , Procedimentos Neurocirúrgicos , Semântica , Tomografia Computadorizada por Raios X , Resultado do Tratamento
18.
Int J Neurosci ; 121(11): 637-9, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21815874

RESUMO

Cardiac involvement, such as conduction defects, is common in myotonic dystrophy type 1 (DM1), but congestive heart failure (CHF) is rare in young patients. A 21-year-old recruit was admitted in the department of cardiology with acute CHF after daily physical exercise for about one week in the boot camp. After recovery, neurologic consultation was requested for his general weakness and lean body mass. He was diagnosed as DM1. He denied any prior cardiac symptoms. We cautiously postulated that excessive physical activity might contribute to develop CHF in DM1 patients. Other possible mechanisms will be discussed. Comprehensive cardiac evaluation might be helpful to identifying high-risk patients early to prevent cardiac complications, even without cardiac symptoms.


Assuntos
Tolerância ao Exercício/genética , Exercício Físico/fisiologia , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Distrofia Miotônica/complicações , Distrofia Miotônica/fisiopatologia , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/etiologia , Fibrilação Atrial/fisiopatologia , Terapia por Exercício/efeitos adversos , Insuficiência Cardíaca/diagnóstico , Humanos , Masculino , Distrofia Miotônica/diagnóstico , Aptidão Física/fisiologia , Adulto Jovem
19.
Epilepsy Behav ; 19(2): 140-5, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20696620

RESUMO

Language function in the postictal state can be successfully assessed and provides valuable information on seizure localization and spread. Several studies have shown that postictal paraphasic errors and ictal speech have value for seizure localization. The Cincinnati method is a simple, repeatable test that involves presenting a single test sentence on a card and asking the patient to read the sentence repeatedly until it is read correctly. It increases the yield of detecting paraphasic errors and ictal speech, and provides a quantitative measure of language recovery known as the postictal language delay, defined as the time from the end of the EEG ictal discharge until the test sentence is read correctly. This language testing method has been used for all patients admitted to the epilepsy monitoring unit at the Cincinnati Epilepsy Center for more than 20 years and has been shown to: (1) lateralize temporal lobe complex partial seizures; (2) identify when temporal lobe complex partial seizures spread to the dominant hemisphere; (3) identify patients with atypical language lateralization; (4) distinguish between temporal and frontal complex partial seizures; and (5) provide some insight into speech prosody changes in nondominant temporal lobe complex partial seizures. The method has some limitations because it requires vigilance of the patient and direct interaction by the technologist, and may be incomplete as a result of patient agitation, but has been successfully completed in more than 80% of patients admitted to the epilepsy monitoring unit. This highly cost-effective test provides important information on seizure localization and spread; is easily taught to technologists, nurses, and family members; and should be added to testing procedures in all epilepsy monitoring units.


Assuntos
Afasia/etiologia , Afasia/fisiopatologia , Idioma , Convulsões/complicações , Afasia/diagnóstico , Eletroencefalografia , Humanos , Testes de Linguagem , Convulsões/fisiopatologia
20.
Technol Health Care ; 28(4): 439-446, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32444584

RESUMO

BACKGROUND: Sleep monitoring is essential to maintain a healthy life, especially for the elderly who want to age well. Among various forms of sleep devices, the non-wearable and home-adapted device might be preferred because it can be easily used. OBJECTIVE: In this study, we evaluated the performance of a non-contact home-adapted device compared to polysomnography (PSG), a gold standard method. METHODS: As a preliminary study, eight subjects were recorded over fourteen nights through PSG. The non-contact home-adapted device comprised a microwave sensor, passive infrared sensor, and smartphone application. Through the device, heart rate, respiratory rate, and body movement were collected and used to estimate sleep stages. Sleep structure was labeled in four classes: wake, REM, light, and deep sleep, and were classified using a weighted k-nearest neighbor algorithm. RESULTS: The device correctly estimated sleep structures with an overall epoch-by-epoch accuracy of 98.65% ± 0.05% based on leave-one-out cross-validation. The device showed significantly positive correlations with PSG in sleep indices including total sleep time, sleep efficiency, and wake after sleep onset. CONCLUSIONS: Our findings demonstrate a good performance of this non-contact and home-adapted device and suggest its suitability for sleep monitoring.


Assuntos
Fases do Sono , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Movimento , Polissonografia
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