RESUMEN
To date, there is no curable treatment option for non-hereditary degenerative cerebellar ataxia. Here we report the case of a patient with sporadic adult-onset ataxia (SAOA) who underwent allogeneic bone marrow-derived mesenchymal stem cell (MSC) therapy via the intrathecal route. A 60-year-old male patient visited our clinic complaining of progressive gait disturbance that commenced two years ago. Upon neurologic examination, the patient exhibited limb dysmetria and gait ataxia. Brain magnetic resonance imaging (MRI) revealed cerebellar atrophy whereas the autonomic function test was normal. The patient was diagnosed with SAOA. The medications that were initially prescribed had no significant effects on the course of this disease and the symptoms deteriorated progressively. At the age of 64, the patient was treated with allogeneic bone marrow-derived MSC therapy. The subsequent K-SARA (Korean version of the Scale for the Assessment and Rating of Ataxia) scores demonstrated a distinct improvement up until 10 months post-administration. No adverse events were reported. The improved post-treatment K-SARA scores may suggest that the MSC therapy can have a neuroprotective effect and that stem cell therapy may serve as a potential therapeutic option for degenerative cerebellar ataxia.
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Ataxia Cerebelosa , Trasplante de Células Madre Hematopoyéticas , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Adulto , Médula Ósea , Ataxia Cerebelosa/terapia , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE AND BACKGROUND: Post-dural puncture headache is the most common significant adverse event following lumbar puncture. In this study, we investigated the possible systemic factors associated with risk for post-dural puncture headache (PDPH). METHODS: We performed a retrospective cohort study in 969 patients who underwent diagnostic lumbar puncture following a standardized protocol. We compared the clinical and laboratory profiles of the post-dural puncture headache group and non-headache group. We also identified independent factors associated with the incidence of post-dural puncture headache. RESULTS: A total of 48 patients (5%) reported headache; 12 of these patients (25%) received a therapeutic epidural blood patch and the remaining 36 patients improved with conservative treatment. After adjusting for other variables that could be related to PDPH, we found that the development of post lumbar puncture headache was independently associated with age (OR: 0.97, 95% CI: 0.95-0.99, P = .001) and serum glucose levels (OR: 0.98, 95% CI: 0.97-0.99, P = .008).When the patients were classified by age, serum glucose levels were persistently lower in patients with PDPH vs those patients without PDPH in all age groups, with more clearly significant differences observed in the elderly (age <30 years, 103.4 mg/dL vs 106.3 mg/dL, P = .716; >60 years, 111.8 mg/dL vs 137.3 mg/dL, P = .023). CONCLUSIONS: Low glucose levels were inversely associated with risk for post-dural puncture headache. Patients with low serum glucose should be carefully monitored for headache after lumbar puncture.
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Glucemia , Parche de Sangre Epidural , Cefalea Pospunción de la Duramadre/diagnóstico , Cefalea Pospunción de la Duramadre/terapia , Sistema de Registros , Adulto , Factores de Edad , Anciano , Parche de Sangre Epidural/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cefalea Pospunción de la Duramadre/epidemiología , Estudios Prospectivos , RiesgoRESUMEN
BACKGROUND: The first aim of our study was to determine whether cortical 18F-florbetaben retention was different between healthy controls and idiopathic normal-pressure hydrocephalus (INPH) patients. Our second aim was to investigate whether there were any relationships between 18F-florbetaben retention and either hippocampal volume or clinical symptoms in INPH patients. METHODS: Seventeen patients diagnosed with INPH and 8 healthy controls underwent studies with magnetic resonance imaging and 18F-florbetaben positron emission tomography imaging. RESULTS: Automated region-of-interest analysis showed significant increases in 18F-florbetaben uptake in several brain regions in INPH patients compared to control subjects, with especially remarkable increases in the frontal (bilateral), parietal (bilateral), and occipital (bilateral) cortices. In the INPH group, right hippocampal volume was found to be negatively correlated with right frontal 18F-florbetaben retention. Korean-Mini Mental State Examination scores negatively correlated with right occipital 18F-florbetaben retention. Higher 18F-florbetaben retention correlated significantly with a higher Clinical Dementia Rating Scale score in the right occipital cortex. CONCLUSIONS: Our results indicate that INPH might be a disease exhibiting a characteristic pattern of cortical 18F-florbetaben retention. 18F-florbetaben retention in the frontal cortex may be related to hippocampal neuronal degeneration. Our findings may also help us understand the potential pathophysiology of cognitive impairments associated with INPH.
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Encéfalo/diagnóstico por imagen , Hidrocéfalo Normotenso/diagnóstico por imagen , Hidrocéfalo Normotenso/patología , Placa Amiloide/diagnóstico por imagen , Anciano , Compuestos de Anilina , Encéfalo/patología , Femenino , Radioisótopos de Flúor , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Placa Amiloide/patología , Tomografía de Emisión de Positrones/métodos , EstilbenosRESUMEN
Lipocalin-2 (LCN2) has diverse functions in multiple pathophysiological conditions; however, its pathogenic role in vascular dementia (VaD) is unknown. Here, we investigated the role of LCN2 in VaD using rodent models of global cerebral ischemia and hypoperfusion with cognitive impairment and neuroinflammation. Mice subjected to transient bilateral common carotid artery occlusion (tBCCAo) for 50 min showed neuronal death and gliosis in the hippocampus at 7 days post-tBCCAo. LCN2 expression was observed predominantly in the hippocampal astrocytes, whereas its receptor was mainly detected in neurons, microglia, and astrocytes. Furthermore, Lcn2-deficient mice, compared with wild-type animals, showed significantly weaker CA1 neuronal loss, cognitive decline, white matter damage, blood-brain barrier permeability, glial activation, and proinflammatory cytokine production in the hippocampus after tBCCAo. Lcn2 deficiency also attenuated hippocampal neuronal death and cognitive decline at 30 days after unilateral common carotid artery occlusion (UCCAo). Furthermore, intracerebroventricular (i.c.v) injection of recombinant LCN2 protein elicited CA1-neuronal death and a cognitive deficit. Our studies using cultured glia and hippocampal neurons supported the decisive role of LCN2 in hippocampal neurotoxicity and microglial activation, and the role of the HIF-1α-LCN2-VEGFA axis of astrocytes in vascular injury. Additionally, plasma levels of LCN2 were significantly higher in patients with VaD than in the healthy control subjects. These results indicate that hippocampal damage and cognitive impairment are mediated by LCN2 secreted from reactive astrocytes in VaD.
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Astrocitos/metabolismo , Disfunción Cognitiva/metabolismo , Demencia Vascular/metabolismo , Hipocampo/metabolismo , Lipocalina 2/metabolismo , Animales , Astrocitos/patología , Biomarcadores/sangre , Células Cultivadas , Cognición/fisiología , Disfunción Cognitiva/patología , Demencia Vascular/patología , Modelos Animales de Enfermedad , Hipocampo/irrigación sanguínea , Hipocampo/patología , Humanos , Lipocalina 2/administración & dosificación , Lipocalina 2/genética , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Microglía/metabolismo , Microglía/patología , Microvasos/metabolismo , Microvasos/patología , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Recent studies have shown a relatively higher prevalence of peripheral neuropathy in idiopathic Parkinson's disease (IPD). The hypothesis is that prolonged levodopa exposure causes vitamin B12 deficiency, which leads to peripheral neuropathy. The aim of our study was to find the relationship between vitamin B12 and its precursor methylmalonic acid (MMA) in IPD patients with neuropathic pain. We performed a cross-sectional study by enrolling consecutive 43 patients who were clinically tested positive for F-18 FP-CIT PET and 15 patients were diagnosed with peripheral neuropathy according to the Toronto clinical scoring system (TCSS). The severity of neuropathic pain was evaluated using total neuropathy scale, revised (TNSr), and Korean Neuropathic Pain Questionnaire (KNPQ). The correlations between age, IPD duration, levodopa equivalent dose (LED), UPDRS III, vitamin B12, MMA, and homocysteine levels were assessed. The prevalence rate of peripheral neuropathy in IPD patients was 35%. Among the serums assessed, MMA levels showed a positive correlation to TNSr and KNPQ in the IPD patients with peripheral neuropathy (TNSr r = 0.882, p < 0.001, KNPQ r = 0.710, p = 0.004), while Vitamin B12 and homocysteine showed no statistically significant correlation. Our study showed a prevalence of peripheral neuropathy in 35% of Korean IPD patients. The serum MMA positively correlated with the severity of neuropathic pain and this can be used as a useful marker in assessment of peripheral neuropathy in Parkinson's disease.
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Ácido Metilmalónico/sangre , Neuralgia/sangre , Neuralgia/complicaciones , Enfermedad de Parkinson/sangre , Enfermedad de Parkinson/complicaciones , Anciano , Antiparkinsonianos/uso terapéutico , Biomarcadores/sangre , Estudios Transversales , Femenino , Homocisteína/sangre , Humanos , Levodopa/uso terapéutico , Masculino , Persona de Mediana Edad , Conducción Nerviosa , Neuralgia/diagnóstico por imagen , Neuralgia/epidemiología , Dimensión del Dolor , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/epidemiología , Prevalencia , Índice de Severidad de la Enfermedad , Vitamina B 12/sangreRESUMEN
BACKGROUND AND PURPOSE: Our aim in this study was to assess whether the frontal assessment battery (FAB) could contribute to the differential diagnosis of cerebrospinal fluid tap test (CSFTT) responders and nonresponders with the hypothesis that CSFTT nonresponders had greater frontal lobe dysfunction. We also explored whether a relationship exists between FAB scores and gait disturbance in idiopathic normal-pressure hydrocephalus (INPH) patients. METHODS: INPH subjects were selected in a consecutive order from a prospectively enrolled INPH registry. Fifty-one INPH patients constituted the final sample for analysis. RESULTS: Logistic regression analysis using the FAB score as independent variable showed a significant influence of the FAB on the differential diagnosis of CSFTT responders and nonresponders (p = 0.025; OR 1.186; 95% CI 1.022-1.377). The FAB scores were negatively correlated with the Timed Up and Go test score (r = -0.382; p = 0.007), 10-meter walking test score (r = -0.351; p = 0.014), Gait Status Scale score (r = -0.382; p = 0.007), and INPH Grading Scale gait score (r = -0.370; p = 0.009). CONCLUSIONS: Our ï¬ndings may indicate a possibility for considering FAB scores in patients with ventriculomegaly as potential cognitive markers for the prediction of CSFTT response. Association between gait function and FAB scores suggests the involvement of similar circuits producing gait symptom and frontal lobe functions in INPH.
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Lóbulo Frontal/fisiopatología , Hidrocéfalo Normotenso/diagnóstico , Pruebas Neuropsicológicas , Punción Espinal , Anciano , Femenino , Lóbulo Frontal/patología , Humanos , Hidrocéfalo Normotenso/complicaciones , Masculino , Persona de Mediana EdadRESUMEN
The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) was developed as a screening instrument for rapid detection of major depression in people with epilepsy (PWE). We evaluated the reliability and validity of the Korean version of the NDDI-E (K-NDDI-E) in Korean PWE. This study applied to 121 outpatients who underwent psychometric tests including the Mini International Neuropsychiatric Interview-Plus Version 5.0.0, Beck Depression Inventory-II (BDI-II), and K-NDDI-E. The K-NDDI-E was easily comprehended and quickly completed by the patients. Cronbach's α coefficient was 0.898. At a cut off score of 11, the K-NDDI-E had a sensitivity of 84.6%, a specificity of 85.3%, a positive predictive value of 61.1%, and a negative predictive value of 95.3%. The scores of the K-NDDI-E had a positive correlation with those of the BDI-II (p<0.001). In conclusion, the K-NDDI-E is a reliable and valid screening tool to detect major depression in Korean PWE.
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Trastorno Depresivo Mayor/diagnóstico , Epilepsia/psicología , Escalas de Valoración Psiquiátrica/normas , Adulto , Trastorno Depresivo Mayor/complicaciones , Epilepsia/complicaciones , Femenino , Humanos , Entrevista Psicológica , Masculino , Psicometría , Reproducibilidad de los Resultados , República de Corea , TraducciónRESUMEN
Idiopathic normal-pressure hydrocephalus (iNPH) is an uncommon neurological disorder with no known pathological hallmarks. INPH may share common degenerative pathways with other neurological diseases, such as Alzheimer's disease (AD). However, the reversible properties of iNPH may share differing pathophysiological mechanisms with other diseases. This study aimed at assessing the diagnostic value of plasma chitinase 3-like 1 (CHI3L1) protein levels as a disease-specific biomarker for iNPH. We selected both iNPH and AD patients as well as normal and disease control subjects from an enrolled dementia registry. A total of 121 AD, 80 iNPH, 13 idiopathic Parkinson's disease, and 23 mild cognitive impairment patients with 83 healthy controls were included in the final analysis. The Aß42, total tau, and phosphorylated tau levels within the cerebrospinal fluid, as well as plasma levels of CHI3L1, were measured using commercially available enzyme-linked immunosorbent assay kits. CHI3L1 levels for iNPH patients were higher than those of the other groups. Analysis of covariance adjusting for age showed significantly increased plasma CHI3L1 levels in iNPH patients than in the controls (p < 0.001). CHI3L1 plasma levels may be useful in differentiating iNPH patients from healthy individuals.
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Proteína 1 Similar a Quitinasa-3/sangre , Hidrocéfalo Normotenso , Biomarcadores/sangre , HumanosRESUMEN
The present study reports two novel genome-wide significant loci for late-onset Alzheimer's disease (LOAD) identified from APOE ε4 non-carrier subjects of East Asian origin. A genome-wide association study of Alzheimer's disease was performed in 2,291 Korean seniors in the discovery phase, from the Gwangju Alzheimer' and Related Dementias (GARD) cohort study. The study was replicated in a Japanese cohort of 1,956 subjects that suggested two novel susceptible SNPs in two genes: LRIG1 and CACNA1A. This study demonstrates that the discovery of AD-associated variants is feasible in non-European ethnic groups using samples comprising fewer subjects from the more homogeneous genetic background.
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Enfermedad de Alzheimer/genética , Apolipoproteínas E/genética , Pueblo Asiatico/genética , Estudio de Asociación del Genoma Completo , Anciano , Canales de Calcio/genética , Estudios de Cohortes , Femenino , Humanos , Japón , Estudios Longitudinales , Masculino , Glicoproteínas de Membrana/genética , Polimorfismo de Nucleótido Simple , República de CoreaRESUMEN
Glial cells are phenotypically heterogeneous non-neuronal components of the central and peripheral nervous systems. These cells are endowed with diverse functions and molecular machineries to detect and regulate neuronal or their own activities by various secreted mediators, such as proteinaceous factors. In particular, glia-secreted proteins form a basis of a complex network of glia-neuron or glia-glia interactions in health and diseases. In recent years, the analysis and profiling of glial secretomes have raised new expectations for the diagnosis and treatment of neurological disorders due to the vital role of glia in numerous physiological or pathological processes of the nervous system. However, there is no online database of glia-secreted proteins available to facilitate glial research. Here, we developed a user-friendly 'Gliome' database (available at www.gliome.org), a web-based tool to access and analyze glia-secreted proteins. The database provides a vast collection of information on 3293 proteins that are released from glia of multiple species and have been reported to have differential functions under diverse experimental conditions. It contains a web-based interface with the following four key features regarding glia-secreted proteins: (i) fundamental information, such as signal peptide, SecretomeP value, functions and Gene Ontology category; (ii) differential expression patterns under distinct experimental conditions; (iii) disease association; and (iv) interacting proteins. In conclusion, the Gliome database is a comprehensive web-based tool to access and analyze glia-secretome data obtained from diverse experimental settings, whereby it may facilitate the integration of bioinformatics into glial research.
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Bases de Datos de Proteínas , Neuroglía/metabolismo , Proteínas , Animales , Humanos , Internet , Proteínas/análisis , Proteínas/química , Proteínas/metabolismo , Programas InformáticosRESUMEN
PURPOSE: Based on the possibility that early-phase florbetaben (E-FBB) brain PET can be a surrogate for brain perfusion imaging, we conducted this study to investigate the clinical utility of E-FBB PET instead of F-FDG brain PET. MATERIALS AND METHODS: This prospective study included 35 patients with clinical suspicion of cognitive decline or dementia and 5 healthy controls. Brain MRI, E-FBB PET, late-phase FBB PET, and FDG PET were acquired. The regional SUV ratios (SUVRs) were calculated by cortical surface region of interest analysis using individual MRI, and relationship between E-FBB and FDG PET was analyzed. All PET scans were scored and analyzed as per visual scoring system, which represent tracer uptake abnormality. Moreover, uptake patterns were analyzed to determine the disease. RESULTS: Among the 40 subjects, 19 were amyloid-positive and 21 were amyloid-negative on late-phase FBB PET. Cortical surface region of interest analysis conducted for comparing between E-FBB and FDG PET revealed significant correlations (P < 0.0001) for regional SUVR among all brain regions; however, the SUVR values of FDG PET were statistically higher than those of E-FBB PET. Similarly, although the visually rated scores for E-FBB and FDG PET showed significant correlation (P < 0.0001), it was considered that the tracer uptake was more severely decreased for FDG PET. The disease types, specified by E-FBB and FDG PET, were statistically correlated. CONCLUSIONS: E-FBB PET could potentially be a useful biomarker for the diagnosis of dementia in place of FDG PET. Nevertheless, the severity of the disease was more accurately determined by FDG PET.
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Compuestos de Anilina , Fluorodesoxiglucosa F18 , Tomografía de Emisión de Positrones/métodos , Estilbenos , Anciano , Amiloide/metabolismo , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Estudios de Casos y Controles , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/metabolismo , Demencia/diagnóstico por imagen , Demencia/metabolismo , Femenino , Humanos , Masculino , Neuroimagen , Estudios Prospectivos , Factores de TiempoRESUMEN
Most cerebellar ataxias (CAs) are incurable neurological disorders, resulting in a lack of voluntary control by inflamed or damaged cerebellum. Although CA can be either directly or indirectly related to cerebellar inflammation, there is no suitable animal model of CA with neuroinflammation. In this study, we evaluated the utility of an intracerebellar injection of lipopolysaccharide (LPS) to generate an animal model of inflammatory CA. We observed that LPS administration induced the expression of pro-inflammatory molecules following activation of glial cells. In addition, the administration of LPS resulted in apoptotic Purkinje cell death and induced abnormal locomotor activities, such as impaired motor coordination and abnormal hindlimb clasping posture. Our results suggest that intracerebellar LPS administration in experimental animals may be useful for studying the inflammatory component of CA.
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Ataxia Cerebelosa/inducido químicamente , Inflamación/inducido químicamente , Lipopolisacáridos/administración & dosificación , Animales , Células Cultivadas , Cerebelo/efectos de los fármacos , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos C57BL , Neuroglía/efectos de los fármacos , Células de Purkinje/efectos de los fármacosRESUMEN
Mesenchymal stem cell (MSC) therapy is a promising alternative approach for the treatment of neurodegenerative diseases, according to its neuroprotective and immunomodulatory potential. Despite numerous clinical trials involving autologous MSCs, their outcomes have often been unsuccessful. Several reports have indicated that MSCs from patients have low capacities in terms of the secretion of neurotrophic or anti-inflammatory factors, which might be associated with cell senescence or disease severity. Therefore, a new strategy to improve their capacities is required for optimal efficacy of autologous MSC therapy. In this study, we compared the secretory potential of MSCs among cerebellar ataxia patients (CA-MSCs) and healthy individuals (H-MSCs). Our results, including secretome analysis findings, revealed that CA-MSCs have lower capacities in terms of proliferation, oxidative stress response, motility, and immunomodulatory functions when compared with H-MSCs. The functional differences were validated in a scratch wound healing assay and neuron-glia co-cultures. In addition, the neuroprotective and immunoregulatory protein follistatin-like 1 (FSTL1) was identified as one of the downregulated proteins in the CA-MSC secretome, with suppressive effects on proinflammatory microglial activation. Our study findings suggest that targeting aspects of the downregulated anti-inflammatory secretome, such as FSTL1, might improve the efficacy of autologous MSC therapy for CA.
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Ataxia Cerebelosa/metabolismo , Regulación hacia Abajo , Proteínas Relacionadas con la Folistatina/metabolismo , Células Madre Mesenquimatosas/metabolismo , Animales , Proliferación Celular , Células Cultivadas , Ataxia Cerebelosa/patología , Humanos , Células Madre Mesenquimatosas/patología , Ratones , Ratones Endogámicos C57BL , Estrés OxidativoRESUMEN
BACKGROUND: Recently, several studies suggested potential involvements of α-synuclein in Alzheimer's disease (AD) pathophysiology. Higher concentrations of α-synuclein were reported in cerebrospinal fluid (CSF) of AD patients with a positive correlation towards CSF tau, indicating its possible role in AD. We analyzed the CSF biomarkers to verify whether α-synuclein could be an additional supported biomarker in AD diagnosis. METHODS: In this cross-sectional study, CSF samples of 71 early-onset AD, 34 late-onset AD, 11 mild cognitive impairment, 17 subjective cognitive decline, 45 Parkinson's disease, and 32 healthy control (HC) were collected. CSF amyloid-ß1-42 (A), total tau (N), and phosphorylated tau181 (T) were measured by commercial ELISA kits, and in-house ELISA kit was developed to quantify α-synuclein. The cognitive assessments and amyloid-PET imaging were also performed. RESULTS: CSF α-synuclein manifested a tendency to increase in AD and to decreased in Parkinson's disease compared to HC. The equilibrium states of total tau and α-synuclein concentrations were changed significantly in AD, and the ratio of total tau/α-synuclein (N/αS) was dramatically increased in AD than HC. Remarkably, N/αS revealed a strong positive correlation with tau phosphorylation rate. Also, the combination of N/αS with amyloid-ß1-42/phosphorylated tau181 ratio had the best diagnosis performance (AUC = 0.956, sensitivity = 96%, specificity = 87%). In concordance analysis, N/αS showed the higher diagnostic agreement with amyloid-ß1-42 and amyloid-PET. Analysis of biomarker profiling with N/αS had distinctive characteristics and clustering of each group. Especially, among the group of suspected non-Alzheimer's disease pathophysiology, all A-T+N+ patients with N/αS+ were reintegrated into AD. CONCLUSIONS: The high correlation of α-synuclein with tau and the elevated N/αS in AD supported the involvement of α-synuclein in AD pathophysiology. Importantly, N/αS improved the diagnostic performance, confirming the needs of incorporating α-synuclein as a biomarker for neurodegenerative disorders. The incorporation of a biomarker group [N/αS] could contribute to provide better understanding and diagnosis of neurodegenerative disorders.
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Enfermedad de Alzheimer , alfa-Sinucleína , Enfermedad de Alzheimer/diagnóstico , Péptidos beta-Amiloides , Biomarcadores , Estudios Transversales , Humanos , Fragmentos de Péptidos , Fosforilación , Proteínas tau/metabolismoRESUMEN
We investigated gait performance utilizing a quantitative gait analysis for 2 groups: (1) idiopathic normal-pressure hydrocephalus (INPH) patients who had a positive response to the cerebrospinal fluid tap test (CSFTT) and (2) healthy controls. The aims of the study were (1) to analyze the characteristics of gait features, (2) to characterize changes in gait parameters before and after the CSFTT, and (3) to determine whether there was any relationship between stride time and stride length variability and Frontal Assessment Battery (FAB) scores in INPH patients. Twenty-three INPH patients and 17 healthy controls were included in this study. Compared with healthy controls, the gait of INPH patients was characterized by lower velocity, shorter stride length, and more broad-based gait. Patients with INPH had a longer stance phase with increased double-limb support. Variability in stride time and stride length was increased in INPH patients. Stride time and stride length variability were correlated with FAB score. After the CSFTT, gait velocity, stride length, and step width significantly improved. There were significant decreases in stride time and stride length variability. These results suggest that the CSFTT for INPH patients might improve the so-called balance-related gait parameter (ie, step width) as well. Stride time and stride length variability also responded to the CSFTT. Association between FAB scores and both stride time and stride length variability suggests involvement of similar circuits producing gait variability and frontal lobe functions in INPH patients.
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Biomarcadores , Análisis de la Marcha , Marcha , Hidrocéfalo Normotenso/líquido cefalorraquídeo , Hidrocéfalo Normotenso/diagnóstico , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Diagnóstico Diferencial , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Femenino , Humanos , Hidrocéfalo Normotenso/etiología , Masculino , PronósticoRESUMEN
Variants in the APOE gene region may explain ethnic differences in the association of Alzheimer's disease (AD) with ε4. Ethnic differences in allele frequencies for three APOE region SNPs (single nucleotide polymorphisms) were identified and tested for association in 19,398 East Asians (EastA), including Koreans and Japanese, 15,836 European ancestry (EuroA) individuals, and 4985 African Americans, and with brain imaging measures of cortical atrophy in sub-samples of Koreans and EuroAs. Among ε4/ε4 individuals, AD risk increased substantially in a dose-dependent manner with the number of APOE promoter SNP rs405509 T alleles in EastAs (TT: OR (odds ratio) = 27.02, p = 8.80 × 10-94; GT: OR = 15.87, p = 2.62 × 10-9) and EuroAs (TT: OR = 18.13, p = 2.69 × 10-108; GT: OR = 12.63, p = 3.44 × 10-64), and rs405509-T homozygotes had a younger onset and more severe cortical atrophy than those with G-allele. Functional experiments using APOE promoter fragments demonstrated that TT lowered APOE expression in human brain and serum. The modifying effect of rs405509 genotype explained much of the ethnic variability in the AD/ε4 association, and increasing APOE expression might lower AD risk among ε4 homozygotes.
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INTRODUCTION: Parkinson disease is associated with various nonmotor symptoms, including rare respiratory dysfunction events. However, patients with Parkinson disease often have comorbid medical problems, such as respiratory distress, and differentiating nonmotor symptoms can be difficult. CASE PRESENTATION: A 78-year-old male presented with repetitive shortness of breath. He was diagnosed with Parkinson disease and chronic obstructive pulmonary disease (COPD) several years prior. His symptoms were ambiguous between acute COPD exacerbation and levodopa-related nonmotor symptoms of Parkinson disease. To clarify the underlying cause, we performed the levodopa challenge test. After the patient complained of dyspnea following levodopa administration, levodopa-induced respiratory dysfunction was diagnosed. After adjusting antiparkinson medication, the patient's respiratory symptoms gradually improved. CONCLUSION: Respiratory dysfunction as a nonmotor symptom of Parkinson disease can be caused by levodopa medication. To determine whether the symptoms are induced by levodopa, the levodopa challenge test may be useful in clarifying symptoms related to antiparkinson medication.
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Antiparkinsonianos/efectos adversos , Levodopa/efectos adversos , Insuficiencia Respiratoria/inducido químicamente , Anciano , Humanos , Masculino , Insuficiencia Respiratoria/diagnósticoRESUMEN
Parkinson's disease (PD) is a chronic progressive disease caused by loss of dopaminergic neurons in the substantia nigra, degenerating the nervous system of a patient over time. Freezing of gait (FOG), which is a form of akinesia, is a symptom of PD. Meanwhile, recent studies show that the gait of PD patients experiencing FOG can be significantly improved by providing the regular visual or auditory patterns for the patients. In this paper, we propose a gait-aid system built upon smart glasses. Our system continuously monitors the gait and so on of a PD patient to detect FOG, and upon detection of FOG it projects visual patterns on the glasses as if the patterns were actually on the floor. Conducting experiments involving ten PD patients, we demonstrate that our system achieves the accuracy of 92.86 % in detecting FOG episodes and that it improves the gait speed and stride length of PD patients by 15.3 â¼ 37.2% and 18.7 â¼ 31.7%, respectively.
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Biorretroalimentación Psicológica/instrumentación , Trastornos Neurológicos de la Marcha/rehabilitación , Rehabilitación Neurológica/instrumentación , Enfermedad de Parkinson/rehabilitación , Teléfono Inteligente , Terapia Asistida por Computador/instrumentación , Anciano , Anciano de 80 o más Años , Biorretroalimentación Psicológica/métodos , Diseño de Equipo , Análisis de Falla de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Rehabilitación Neurológica/métodos , Resultado del Tratamiento , Interfaz Usuario-ComputadorRESUMEN
BACKGROUND AND PURPOSE: Our aims were to analyze the characteristics of parkinsonian features and to characterize changes in parkinsonian motor symptoms before and after the cerebrospinal fluid tap test (CSFTT) in idiopathic normal-pressure hydrocephalus (INPH) patients. METHODS: INPH subjects were selected in consecutive order from a prospectively enrolled INPH registry. Fifty-five INPH patients (37 males) having a positive response to the CSFTT constituted the final sample for analysis. The mean age was 73.7±4.7 years. The pre-tap mean Unified Parkinson's Disease Rating Scale motor (UPDRS-III) score was 24.5±10.2. RESULTS: There was no significant difference between the upper and lower body UPDRS-III scores (p=0.174). The parkinsonian signs were asymmetrical in 32 of 55 patients (58.2%). At baseline, the Timed Up and Go Test and 10-meter walking test scores were positively correlated with the total motor score, global bradykinesia score, global rigidity score, upper body score, lower body score, and postural instability/gait difficulties score of UPDRS-III. After the CSFTT, the total motor score, global bradykinesia score, upper body score, and lower body score of UPDRS-III significantly improved (p<0.01). There was a significant decrease in the number of patients with asymmetric parkinsonism (p<0.05). CONCLUSIONS: In the differential diagnosis of elderly patients presenting with asymmetric and upper body parkinsonism, we need to consider a diagnosis of INPH. The association between gait function and parkinsonism severity suggests the involvement of similar circuits producing gait and parkinsonian symptoms in INPH.