RESUMEN
Sarcopenia, which refers to the muscle loss that accompanies aging, is a complex neuromuscular disorder with a clinically high prevalence and mortality. Despite many efforts to protect against muscle weakness and muscle atrophy, the incidence of sarcopenia and its related permanent disabilities continue to increase. In this study, we found that treatment with human placental hydrolysate (hPH) significantly increased the viability (approximately 15%) of H2 O2 -stimulated C2C12 cells. Additionally, while H2 O2 -stimulated cells showed irregular morphology, hPH treatment restored their morphology to that of cells cultured under normal conditions. We further showed that hPH treatment effectively inhibited H2 O2 -induced cell death. Reactive oxygen species (ROS) generation and Mstn expression induced by oxidative stress are closely associated with muscular dysfunction followed by atrophy. Exposure of C2C12 cells to H2 O2 induced abundant production of intracellular ROS, mitochondrial superoxide, and mitochondrial dysfunction as well as myostatin expression via nuclear factor-κB (NF-κB) signaling; these effects were attenuated by hPH. Additionally, hPH decreased mitochondria fission-related gene expression (Drp1 and BNIP3) and increased mitochondria biogenesis via the Sirt1/AMPK/PGC-1α pathway and autophagy regulation. In vivo studies revealed that hPH-mediated prevention of atrophy was achieved predominantly through regulation of myostatin and PGC-1α expression and autophagy. Taken together, our findings indicate that hPH is potentially protective against muscle atrophy and oxidative cell death.
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Antioxidantes/farmacología , Músculo Esquelético/efectos de los fármacos , Atrofia Muscular/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Placenta , Extractos de Tejidos/farmacología , Animales , Autofagia/efectos de los fármacos , Línea Celular , Modelos Animales de Enfermedad , Femenino , Humanos , Masculino , Ratones Pelados , Mitocondrias Musculares/efectos de los fármacos , Mitocondrias Musculares/metabolismo , Mitocondrias Musculares/patología , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Atrofia Muscular/metabolismo , Atrofia Muscular/patología , Miostatina/metabolismo , FN-kappa B/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , EmbarazoRESUMEN
OBJECTIVES: To evaluate the validity of the revised 2017 McDonald criteria for multiple sclerosis (MS) compared with the 2010 McDonald criteria to predict conversion to clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndrome (CIS). METHODS: A total of 163 patients from seven referral hospitals in Korea, who experienced a first clinical event suggestive of MS between 2006 and 2017, were enrolled. Patients were stratified into two groups according to outcome at the last visit: CDMS converters who experienced a second clinical event and non-converters. RESULTS: Of the 163 patients with a mean follow-up of 63 months, 60% converted to CDMS. The sensitivity, specificity, positive and negative predictive values and accuracy were, respectively, 88.8%, 43.1%, 70.2%, 71.8% and 70.6% for the 2017 McDonald criteria and 53.1%, 69.2%, 72.2%, 49.5% and 59.5% for the 2010 McDonald criteria. After exclusion of 82 patients who received disease-modifying agents before the second attack, the specificity of the 2017 and 2010 McDonald criteria increased to 85.0% and 95.0%, but sensitivity decreased to 83.6% and 47.5%, respectively. CONCLUSION: The 2017 McDonald criteria afforded higher sensitivity and accuracy but lower specificity compared with the 2010 McDonald criteria for prediction of conversion to CDMS in Korean CIS patients.
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Enfermedades Desmielinizantes/diagnóstico por imagen , Esclerosis Múltiple/diagnóstico , Adolescente , Adulto , Crotonatos/uso terapéutico , Enfermedades Desmielinizantes/líquido cefalorraquídeo , Enfermedades Desmielinizantes/tratamiento farmacológico , Progresión de la Enfermedad , Femenino , Clorhidrato de Fingolimod/uso terapéutico , Acetato de Glatiramer/uso terapéutico , Humanos , Hidroxibutiratos , Factores Inmunológicos/uso terapéutico , Inmunosupresores/uso terapéutico , Interferón beta/uso terapéutico , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/líquido cefalorraquídeo , Esclerosis Múltiple/diagnóstico por imagen , Nitrilos , Bandas Oligoclonales/líquido cefalorraquídeo , Neuritis Óptica/líquido cefalorraquídeo , Neuritis Óptica/diagnóstico por imagen , Quinolonas/uso terapéutico , Reproducibilidad de los Resultados , República de Corea , Sensibilidad y Especificidad , Factores de Tiempo , Toluidinas/uso terapéutico , Adulto JovenRESUMEN
BACKGROUND: Multiple sclerosis (MS) is an immune-associated inflammatory disorder of the central nervous system and results in serious disability. Although many disease-modifying therapy drugs have been developed, these drugs have shown limited clinical efficacy and some adverse effects in previous studies, therefore, there has been reasonable need for less harmful and cost-effective therapeutics. Herein, we tested the anti-inflammatory effect of sulforaphane (SFN) in a mouse model of experimental autoimmune encephalomyelitis (EAE). METHODS: The EAE mice were randomly assigned into two experimental groups: the phosphate-buffered saline (PBS)-treated EAE group and SFN-treated EAE group. After EAE mice induction by auto-immunization against the myelin oligodendrocyte glycoprotein peptide, we evaluated EAE symptom scores and biochemical analyses such as infiltration of inflammatory cells and demyelination of the spinal cord. Furthermore, western blotting was performed using the spinal cords of EAE mice. RESULTS: In the behavioral study, the SFN-treated EAE mice showed favorable clinical scores compared with PBS-treated EAE mice at the 13th day (1.30 ± 0.15 vs. 1.90 ± 0.18; P = 0.043) and 14th day (1.80 ± 0.13 vs. 2.75 ± 0.17; P = 0.003). Additionally, the biochemical studies revealed that SFN treatment inhibited the inflammatory infiltration, demyelinating injury of the spinal cords, and the up-regulation of inducible nitric oxide synthase in the EAE mice. CONCLUSION: The SFN treatment showed anti-inflammatory and anti-oxidative effects in the EAE mice. Conclusively, this study suggests that SFN has neuroprotective effects via anti-inflammatory processing, so it could be a new therapeutic or nutritional supplement for MS.
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Antiinflamatorios/farmacología , Conducta Animal/efectos de los fármacos , Encefalomielitis Autoinmune Experimental/patología , Isotiocianatos/farmacología , Animales , Antiinflamatorios/uso terapéutico , Cuello del Útero/efectos de los fármacos , Cuello del Útero/patología , Progresión de la Enfermedad , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Femenino , Isotiocianatos/uso terapéutico , Ratones , Ratones Endogámicos C57BL , Óxido Nítrico Sintasa de Tipo II/metabolismo , Médula Espinal/efectos de los fármacos , Médula Espinal/patología , Sulfóxidos , Regulación hacia Arriba/efectos de los fármacosRESUMEN
OBJECTIVES: We compared validity of 2010 McDonald and newly proposed 2016 Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) criteria for dissemination in space (DIS) in predicting the conversion to clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndrome (CIS). METHODS: Between 2006 and 2016, we enrolled 170 patients who had a first clinical event suggestive of multiple sclerosis (MS) from seven referral hospitals in Korea. Patients were classified into two groups based on the main outcome at the last follow-up: CDMS converters, who experienced a second attack, and non-converters. RESULTS: Of 170 patients with mean follow-up duration of 54 months, 51% converted to CDMS. The sensitivity, specificity, accuracy, and positive and negative predictive values of 2010 McDonald criteria were 70.9%, 63.1%, 67.1%, 66.3%, and 67.9%, and those for 2016 MAGNIMS criteria were 88.4%, 46.4%, 67.7%, 62.8%, and 79.6%, respectively. When we excluded 80 patients who underwent disease-modifying therapy before the second clinical event, the specificity increased to 92.3% and 84.6%, but the sensitivity decreased to 58.8% and 82.4% for 2010 McDonald and 2016 MAGNIMS criteria, respectively. CONCLUSION: 2016 MAGNIMS magnetic resonance imaging (MRI) criteria for DIS showed higher sensitivity but lower specificity than 2010 McDonald criteria in predicting conversion to CDMS in CIS patients.
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Enfermedades Desmielinizantes/diagnóstico por imagen , Enfermedades Desmielinizantes/patología , Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patología , Adolescente , Adulto , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , República de Corea , Sensibilidad y Especificidad , Adulto JovenRESUMEN
BACKGROUND: The motor and sensory symptoms caused by compressive radial neuropathy are well-known, but the involvement of the autonomic nervous system or the dermatologic symptoms are less well known. We report an unusual case of compressive radial neuropathy with reversible reddish skin color change. CASE PRESENTATION: A 42-year-old man was referred for left wrist drop, finger drop and a tingling sensation over the lateral dorsum of the left hand. Based on clinical information, neurologic examinations and electrophysiologic studies, he was diagnosed with compressive radial neuropathy. In addition, a reddish skin color change was observed at the area of radial sensory distribution. After two weeks of observation without specific treatment, the skin color had recovered along with a marked improvement in weakness and aberrant sensation. CONCLUSIONS: Compressive radial neuropathy with a reversible reddish skin color change is unusual and is considered to be due to vasomotor dysfunction of the radial autonomic nerve. Compressive radial neuropathy is presented with not only motor and sensory symptoms but also autonomic symptoms; therefore, careful examination and inspection are needed at diagnosis.
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Sistema Nervioso Autónomo/fisiopatología , Neuropatía Radial/fisiopatología , Pigmentación de la Piel/fisiología , Piel/fisiopatología , Adulto , Humanos , MasculinoRESUMEN
BACKGROUND: There are currently few studies regarding late-onset neuromyelitis optica spectrum disorder (LO-NMOSD). OBJECTIVE: We aimed to describe the characteristic features of patients with LO-NMOSD in Korea. METHODS: Anti-aquaporin-4 antibody-positive patients with neuromyelitis optica spectrum disorder (NMOSD) from nine tertiary hospitals were reviewed retrospectively. The patients were divided into two groups based on age of onset: LO-NMOSD (⩾50 years of age at onset) versus early-onset neuromyelitis optica spectrum disorder (EO-NMOSD) (<50 years of age at onset). Clinical, laboratory, and magnetic resonance imaging (MRI) parameters were investigated. RESULTS: Among a total of 147 patients (125 female; age of onset, 39.4 ± 15.2 years), 45 patients (30.6%) had an age of onset of more than 50 years. Compared to patients with EO-NMOSD, patients with LO-NMOSD had more frequent isolated spinal cord involvement at onset (64.4% vs 37.2%, p = 0.002), less frequent involvement of the optic nerve (40.0% vs 67.7%, p = 0.002), and less frequent brain MRI lesions (31.1% vs 50.0%, p = 0.034). Furthermore, there was a significant positive correlation between age of onset and Expanded Disability Status Scale (EDSS) score at last follow-up ( r = 0.246, p = 0.003). CONCLUSION: Age of onset could be an important predictor of lesion location and clinical course of patients with NMOSD.
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Acuaporina 4/inmunología , Autoanticuerpos/sangre , Neuromielitis Óptica , Índice de Severidad de la Enfermedad , Adulto , Edad de Inicio , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neuromielitis Óptica/sangre , Neuromielitis Óptica/epidemiología , Neuromielitis Óptica/patología , Neuromielitis Óptica/fisiopatología , República de Corea/epidemiología , Estudios RetrospectivosRESUMEN
Multiple sclerosis (MS) is a T-lymphocyte-mediated autoimmune disease that is characterized by inflammation in the central nervous system (CNS). Although many disease-modifying therapies (DMTs) are presumed effective in patients with MS, studies on the efficacy and safety of DMTs for preventing MS relapse are limited. Therefore, we tested the immunosuppressive anti-inflammatory effects of oral-formulated tacrolimus (FK506) on MS in a mouse model of experimental autoimmune encephalomyelitis (EAE). The mice were randomly divided into 3 experimental groups: an untreated EAE group, a low-dose tacrolimus-treated EAE group, and a high-dose tacrolimus-treated EAE group. After autoimmunization of the EAE mice with myelin oligodendrocyte glycoprotein, symptom severity scores, immunohistochemistry of the myelination of the spinal cord, and western blotting were used to evaluate the EAE mice. After the autoimmunization, the symptom scores of each EAE group significantly differed at times. The group treated with the larger tacrolimus dose had the lowest symptom scores. The tacrolimus-treated EAE groups exhibited less demyelination and inflammation and weak immunoreactivity for all of the immunization biomarkers. Our results revealed that oral-formulated tacrolimus inhibited the autoimmunization in MS pathogenesis by inactivating inflammatory cells.
Asunto(s)
Antiinflamatorios/uso terapéutico , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Tacrolimus/uso terapéutico , Administración Oral , Animales , Antiinflamatorios/química , Biomarcadores/metabolismo , Antígenos CD4/metabolismo , Proteínas de Unión al Calcio/metabolismo , Composición de Medicamentos , Encefalomielitis Autoinmune Experimental/patología , Femenino , Proteína Ácida Fibrilar de la Glía/metabolismo , Inmunohistoquímica , Ratones , Ratones Endogámicos C57BL , Proteínas de Microfilamentos/metabolismo , Glicoproteína Mielina-Oligodendrócito/efectos adversos , Índice de Severidad de la Enfermedad , Médula Espinal/patología , Tacrolimus/químicaRESUMEN
BACKGROUND: We investigated the incidence and risk factors of early neurological worsening according to ischemia progression among acute cerebral infarction patients after intravenous thrombolysis. METHODS: The medical records of consecutive cerebral infarction patients treated with intravenous thrombolysis from 2 university hospitals were reviewed. Early neurological deterioration (END) was defined as 2 or more National Institutes of Health Stroke Scale aggravations within 24 hours after thrombolysis, and its etiologies were categorized by follow-up imaging into 3 groups: ischemia progression, symptomatic hemorrhage, and brain edema. We compared clinical variables between the group of patients with ischemia progression and the patients without neurological deterioration to derive etiology-specific risk factors. RESULTS: A total of 210 patients were included in this study, with 57 (26.2%) patients experiencing neurological deterioration. The prevalence of patients with END due to ischemia progression (27 patients, 12.9%) outnumbered the prevalence of patients with neurological deterioration due to symptomatic hemorrhage (n = 13) or brain edema (n = 15). Compared to the group of patients without END, the patients with ischemia progression were more likely to have a stroke subtype of large-artery atherosclerosis, to be current smokers, and to have less severe initial neurological deficits. Multivariate logistic regression analysis revealed that large-artery atherosclerosis was an independent predictor of END due to ischemia progression (odds ratio = 3.8, confidence interval = 1.6-9.3). CONCLUSIONS: A major contributor to END within 24 hours after intravenous thrombolysis was ischemia progression, and the stroke subtype of large-artery atherosclerosis predicted ischemia progression.
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Edema Encefálico/etiología , Isquemia Encefálica/tratamiento farmacológico , Fibrinolíticos/efectos adversos , Hemorragias Intracraneales/etiología , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica/efectos adversos , Activador de Tejido Plasminógeno/efectos adversos , Administración Intravenosa , Adulto , Anciano , Anciano de 80 o más Años , Edema Encefálico/epidemiología , Edema Encefálico/patología , Isquemia Encefálica/patología , Progresión de la Enfermedad , Femenino , Fibrinolíticos/uso terapéutico , Humanos , Incidencia , Hemorragias Intracraneales/epidemiología , Hemorragias Intracraneales/patología , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/patología , Activador de Tejido Plasminógeno/uso terapéuticoRESUMEN
BACKGROUND AND PURPOSE: The aim of this study was to determine the association between 25-hydroxyvitamin D (25(OH)D) and neuroimaging correlates of cerebral small vessel disease. METHODS: We identified 759 consecutive patients with acute ischemic stroke or transient ischemic attack. Lacunes, white matter hyperintensity, and cerebral microbleed (CMB) were assessed using MR images. Deep CMB was defined as the presence of CMB in basal ganglia, thalamus, or brain stem. The association between 25(OH)D and small vessel disease was tested using linear and logistic regression analyses. RESULTS: Mean age was 68 (±13) years. Mean level of 25(OH)D was 34.1±17.8 nmol/L. On bivariate analysis, a 25-nmol/L decrease in 25(OH)D was associated with lacunes (regression coefficient, 0.23; 95% confidence interval [CI], 0.02-0.45), severe white matter hyperintensity (odds ratio, 2.05; 95% CI, 1.41-3.08), and deep CMB (odds ratio, 1.28; 95% CI, 1.01-1.63). Also, 25(OH)D deficiency (≤25 nmol/L) was associated with lacunes (regression coefficient, 0.5; 95% CI, 0.04-0.95), severe white matter hyperintensity (odds ratio, 2.74; 95% CI, 1.31-6.45), and deep CMB (odds ratio, 1.68; 95% CI, 1.03-2.78). The association remained significant even after multivariable adjustment and in the subgroup of previously healthy patients. CONCLUSIONS: 25(OH)D is inversely associated with lacunes, white matter hyperintensity, and deep CMB. Our findings suggest that 25(OH)D is linked to small vessel disease, and in future trials it should be tested whether 25(OH)D supplementation can prevent small vessel disease.
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Encéfalo/patología , Hemorragia Cerebral/epidemiología , Enfermedades de los Pequeños Vasos Cerebrales/epidemiología , Ataque Isquémico Transitorio/epidemiología , Accidente Cerebrovascular/epidemiología , Deficiencia de Vitamina D/epidemiología , Vitamina D/análogos & derivados , Sustancia Blanca/patología , Anciano , Anciano de 80 o más Años , Ganglios Basales/patología , Tronco Encefálico/patología , Hemorragia Cerebral/patología , Enfermedades de los Pequeños Vasos Cerebrales/patología , Estudios de Cohortes , Femenino , Humanos , Ataque Isquémico Transitorio/patología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Accidente Cerebrovascular/patología , Tálamo/patología , Vitamina D/sangre , Deficiencia de Vitamina D/sangreRESUMEN
INTRODUCTION: The motor unit number index (MUNIX) refers to an electrophysiological method that measures the number of motor units in the surface electromyographic interference pattern (SIP) recorded during graded muscle contractions. MUNIX studies of limb muscles have been conducted, but MUNIX studies of bulbo-facial muscles have not been reported. METHODS: We assessed bilateral orbicularis oculi muscles using MUNIX, and the reference values and reproducibility of MUNIX and motor unit size index (MUSIX) were investigated in healthy subjects. RESULTS: In this study, MUNIX was applied successfully to the orbicularis oculi muscles and showed good reproducibility. The correlation coefficients for MUNIX and MUSIX were 0.803 and 0.592, respectively, and the coefficients of variation were 20.9% and 8.5%, respectively. CONCLUSIONS: The MUNIX procedure for the orbicularis oculi muscle would be a useful tool for evaluating bulbar symptoms, especially in amyotrophic lateral sclerosis.
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Músculos Faciales/fisiología , Neuronas Motoras/fisiología , Contracción Muscular/fisiología , Potenciales de Acción/fisiología , Adulto , Estimulación Eléctrica , Electromiografía , Femenino , Voluntarios Sanos , Humanos , Masculino , Adulto JovenRESUMEN
INTRODUCTION: Split hand is considered to be a specific feature of amyotrophic lateral sclerosis (ALS). METHODS: We evaluated the pattern difference of intrinsic hand muscles of upper limb-onset ALS (UL-ALS), upper limb-onset progressive muscular atrophy (UL-PMA), brachial amyotrophic diplegia (BAD), and Hirayama disease (HD) by measuring objective electrophysiological markers. RESULTS: The abductor digiti minimi (ADM)/abductor pollicis brevis (APB) compound muscle action potential (CMAP) amplitude ratio was significantly higher in UL-ALS than other variants, but a considerable proportion of UL-ALS cases had an amplitude ratio in the range of other variants. Absent APB CMAP and abnormally high ADM/APB CMAP amplitude ratio (≥4) occurred only with UL-ALS. Conversely, an absent ADM CMAP was identified only in UL-PMA and BAD. CONCLUSIONS: The absolute ADM/APB CMAP amplitude ratio was not specific for ALS; however, several findings from simple electrophysiological measurements may help predict prognosis in patients with motor neuron diseases and may be early diagnostic markers for ALS.
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Esclerosis Amiotrófica Lateral/diagnóstico , Esclerosis Amiotrófica Lateral/epidemiología , Mano/patología , Atrofia Muscular/diagnóstico , Atrofia Muscular/epidemiología , Potenciales de Acción/fisiología , Adolescente , Adulto , Anciano , Esclerosis Amiotrófica Lateral/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Atrofia Muscular/fisiopatología , Estudios Retrospectivos , Adulto JovenRESUMEN
We investigated the validity of the 2005 and 2010 McDonald magnetic resonance imaging (MRI) criteria for dissemination in space (DIS) to predict the conversion of clinically definite multiple sclerosis (CDMS) in 94 Korean patients with clinically isolated syndromes (CIS). The sensitivity, specificity, accuracy, positive and negative predictive values of the 2005, 2010 McDonald DIS criteria were comparable to those observed in the Caucasian population. This finding suggests that after careful exclusion of alternative explanations, particularly neuromyelitis optica (NMO) and NMO spectrum disorder (NMOSD), both the 2005 and 2010 McDonald DIS criteria are also useful to predict conversion to CDMS in Korean patients with CIS.
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Enfermedades Desmielinizantes/diagnóstico , Imagen por Resonancia Magnética , Esclerosis Múltiple/diagnóstico , Adolescente , Adulto , Pueblo Asiatico , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , República de Corea , Adulto JovenRESUMEN
BACKGROUND: The Expanded Disability Status Scale (EDSS) is the most widely employed ordinal disability scale in multiple sclerosis (MS). However, how far apart the individual EDSS levels are along the disability spectrum has not been formally quantified. OBJECTIVES: The objective of this paper is to generate refined disability weights (DWs) for each of the ordinal EDSS levels. METHODS: We performed the person trade-off (PTO) procedure to derive DWs of five representative EDSS categories (2, 4, 6, 7 and 9), and DWs of the remaining EDSS categories were assigned by linear interpolation. The modified Delphi process was used to achieve consensus among raters. RESULTS: DWs were 0.021 for EDSS 2, 0.199 for EDSS 4, 0.313 for EDSS 6, 0.617 for EDSS 7, and 0.926 for EDSS 9. Panel members achieved a high degree of consensus for each DW, as indicated by low coefficients of variation. CONCLUSIONS: Our DWs confirmed that EDSS is an ordinal scale with highly variable intervals. The availability of DW for each EDSS level allows direct comparison of each MS outcome state with other health states and provides a foundation for the estimation of the disability-adjusted life-years lost of individual patients.
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Evaluación de la Discapacidad , Esclerosis Múltiple/diagnóstico , Personas Encamadas , Técnica Delphi , Deambulación Dependiente , Humanos , Limitación de la Movilidad , Esclerosis Múltiple/fisiopatología , Variaciones Dependientes del Observador , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Índice de Severidad de la EnfermedadRESUMEN
Glycogen synthase kinase-3ß (GSK-3ß) has been identified as one of the important pathogenic mechanisms in motor neuronal death. GSK-3ß inhibitor has been investigated as a modulator of apoptosis and has been shown to confer significant protective effects on cell death in neurodegenerative diseases. However, GSK-3ß is known to have paradoxical effects on apoptosis subtypes, i.e., pro-apoptotic in mitochondrial-associated intrinsic apoptosis, but anti-apoptotic in death receptor-related extrinsic apoptosis. In this study, we evaluated the effect of a new GSK-3ß inhibitor (JGK-263) on motor neuron cell survival and apoptosis, by using low to high doses of JGK-263 after 48 h of serum withdrawal, and monitoring changes in extrinsic apoptosis pathway components, including Fas, FasL, cleaved caspase-8, p38α, and the Fas-Daxx interaction. Cell survival peaked after treatment of serum-deprived cells with 50 µM JGK-263. The present study showed that treatment with JGK-263 reduced serum-deprivation-induced motor neuronal apoptosis by inactivating not only the intrinsic, but also the extrinsic apoptosis pathway. These results suggest that JGK-263 has a neuroprotective effect through effective modulation of the extrinsic apoptosis pathway in motor neuron degeneration.
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Apoptosis/efectos de los fármacos , Glucógeno Sintasa Quinasa 3/antagonistas & inhibidores , Neuronas Motoras/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Ratones , Neuronas Motoras/citología , Neuronas Motoras/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Multiple sclerosis (MS) in Asia is thought to have different clinical characteristics from MS in Western countries; however, previous studies in Asia were performed without properly differentiating neuromyelitis optica (NMO) from MS. OBJECTIVES: To evaluate the clinical characteristics of MS in Korea after careful exclusion of potential explanations other than MS, particularly NMO spectrum disorder (NMOSD). METHODS: This study is a retrospective review of consecutive MS patients attending five referral hospitals in Korea. All patients' MS diagnoses were re-evaluated. RESULTS: Of the 105 patients, 70 were female and 35 were male. The mean age of onset was 30.4 years and the mean disease duration was 5.4 years. On initial magnetic resonance imaging (MRI), 58% and 64% fulfilled the criteria for dissemination in space for the 2005 and 2010 McDonald criteria, respectively. Spinal cord lesions were observed in 78% of patients, primarily present as multiple small lesions with a mean length of 0.9 vertebral segments. The median time from disease onset to an Expanded Disability Status Scale 6 was 20 years. CONCLUSIONS: After careful exclusion of NMOSD, we found that the clinical pattern of MS in Korea does not fundamentally differ from that seen in Western countries.
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Esclerosis Múltiple/epidemiología , Esclerosis Múltiple/patología , Adulto , Edad de Inicio , Pueblo Asiatico , Estudios de Cohortes , Femenino , Humanos , Factores Inmunológicos/uso terapéutico , Corea (Geográfico)/epidemiología , Imagen por Resonancia Magnética , Masculino , Esclerosis Múltiple/tratamiento farmacológico , Prevalencia , Estudios Retrospectivos , Resultado del Tratamiento , Población BlancaAsunto(s)
Síndrome de Creutzfeldt-Jakob/complicaciones , Síndrome de Creutzfeldt-Jakob/diagnóstico por imagen , Esquizofrenia/fisiopatología , Encéfalo/diagnóstico por imagen , Conducta Compulsiva/etiología , Estudios de Seguimiento , Alucinaciones/etiología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Examen NeurológicoRESUMEN
BACKGROUND: We aimed to evaluate the diagnostic accuracy of enzyme-linked immunosorbent assay (ELISA) for anti-muscle specific tyrosine kinase (MuSK) antibody (Ab) in a large cohort of anti-acetylcholine receptor (AChR) Ab-negative generalized myasthenia gravis (MG), and also to investigate clinical contexts for the diagnosis of MuSK MG. METHODS: A retrospective study of 160 patients with a clinical suspicion of AChR Ab-negative generalized MG was performed. The serum samples were tested for anti-clustered AChR Ab by cell-based assay (CBA), anti-MuSK Ab by ELISA, CBA and/or radioimmunoprecipitation assay (RIPA). Clinical data were compared between anti-MuSK Ab-positive MG and double seronegative (AChR and MuSK) MG groups. RESULTS: After excluding non-MG and clustered AChR Ab-positive patients, we identified 89 patients as a cohort of AChR Ab-negative generalized MG. Anti-MuSK Ab was positive by ELISA in 22 (24.7%) patients. While CBA identified five additional anti-MuSK Ab-positive patients, the results of ELISA were mostly consistent with CBA and RIPA with Cohen's kappa of 0.80 and 0.90, respectively (p < 0.001). The most frequent differential diagnosis was motor neuron disease particularly of bulbar onset which showed remarkably overlapping clinical and electrophysiological features with MuSK MG at presentation. CONCLUSION: While confirming the highest sensitivity of CBA for detecting anti-MuSK Ab, our results highlight the clinical pitfalls in making a diagnosis of MuSK MG and may support a diagnostic utility of MuSK-ELISA in clinical practice.
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Miastenia Gravis , Proteínas Tirosina Quinasas Receptoras , Humanos , Estudios Retrospectivos , Receptores Colinérgicos , Autoanticuerpos , Ensayo de Inmunoadsorción EnzimáticaAsunto(s)
Neuropatías del Plexo Braquial/diagnóstico , Bursitis/diagnóstico por imagen , Conducción Nerviosa , Neuralgia/diagnóstico , Dolor de Hombro/diagnóstico , Potenciales de Acción , Anciano , Neuropatías del Plexo Braquial/etiología , Neuropatías del Plexo Braquial/fisiopatología , Bursitis/complicaciones , Bursitis/fisiopatología , Electromiografía , Femenino , Humanos , Imagen por Resonancia Magnética , Neuralgia/etiología , Neuralgia/fisiopatología , Dolor de Hombro/etiología , Dolor de Hombro/fisiopatologíaRESUMEN
BACKGROUND: Assessment of frontal lobe impairment in amyotrophic lateral sclerosis (ALS) is a matter of great importance, since it often causes ALS patients to decrease medication and nursing compliance, thus shortening their survival time. METHODS: The frontal assessment battery (FAB) is a short and rapid method for assessing frontal executive functions. We investigated the applicability of the FAB as a screening method for assessing cognitive impairments in 61 ALS patients. Depending on the results of the FAB, we classified patients into two subgroups: FAB-normal and FAB-abnormal. We then performed additional evaluations of cognitive function using the Korean version of the mini-mental state examination (K-MMSE), a verbal fluency test (COWAT), and a neuropsychiatric inventory (NPI). Results of these tests were compared between the two groups using Mann-Whitney U-tests, and Spearman correlation analyses were used to investigate the relationships between FAB score and disease duration and severity. RESULTS: Of the 61 sporadic ALS patients included in this study, 14 were classified as FAB-abnormal and 47 were classified as FAB-normal. The FAB-normal and FAB-abnormal patients performed significantly differently in all domains of the COWAT. There was no difference in behavioral disturbance, as assessed by the NPI, between the two groups. The FAB scores were found to significantly correlate with both disease duration and severity. CONCLUSIONS: The FAB shows promise as a method of screening for frontal lobe dysfunction in ALS, as it is not only quick and easy, but also reliable. Additional studies should examine how FAB performance changes as ALS progresses.
Asunto(s)
Esclerosis Amiotrófica Lateral/complicaciones , Esclerosis Amiotrófica Lateral/patología , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/etiología , Lóbulo Frontal/fisiopatología , Adulto , Anciano , Femenino , Lóbulo Frontal/patología , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Estadísticas no Paramétricas , Adulto JovenRESUMEN
We report a case of 54-yr-old woman who presented with 4-extremities weakness and sensory changes, followed by cervical spinal cord lesion in magnetic resonance imaging. Based on the suspicion of spinal tumor, spinal cord biopsy was performed, and the histology revealed multinucleated giant cells, lymphocytes and aggregated histiocytes within granulomatous inflammation, consistent with non-caseating granuloma seen in sarcoidosis. The patient was treated with corticosteroid, immunosuppressant and thalidomide for years. Our case indicates that diagnosis of spinal cord sarcoidosis is challenging and may require histological examination, and high-dose corticosteroid and immunosuppressant will be a good choice in the treatment of spinal cord sarcoidosis, and the thalidomide has to be debated in the spinal cord sarcoidosis.