RESUMO
Human T-cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients may have brain white matter (WM) lesions, but the association of these lesions with disease activity is poorly understood. We retrospectively evaluated the brain WM lesions of 22 HAM/TSP patients (male 4: female 18) including 5 rapid progressors, 16 slow progressors, and 1 very slow progressor. The severity of WM brain lesions on axial Fluid Attenuated Inversion Recovery images was evaluated utilizing the Fazekas scale, cerebrospinal fluid biomarkers, and proviral load in peripheral blood mononuclear cells. Imaging and biological data were compared at the first visit and a subsequent visit more than 4 years later. Patients with comorbidities including adult T-cell leukemia-lymphoma and cerebrovascular disease were excluded. The results revealed that brain WM lesions in the rapid progressors group were more pronounced than those in slow progressors. In patients with HAM/TSP, severe and persistent inflammation of the spinal cord may cause brain WM lesions.
RESUMO
Background: Alzheimer's disease (AD), the most prevalent form of dementia, is a debilitating, progressive neurodegeneration. Amino acids play a wide variety of physiological and pathophysiological roles in the nervous system, and their levels and disorders related to their synthesis have been related to cognitive impairment, the core feature of AD. Our previous multicenter trial showed that hachimijiogan (HJG), a traditional Japanese herbal medicine (Kampo), has an adjuvant effect for Acetylcholine estelase inhibitors (AChEIs) and that it delays the deterioration of the cognitive dysfunction of female patients with mild AD. However, there are aspects of the molecular mechanism(s) by which HJG improves cognitive dysfunction that remain unclear. Objectives: To elucidate through metabolomic analysis the mechanism(s) of HJG for mild AD based on changes in plasma metabolites. Methods: Sixty-seven patients with mild AD were randomly assigned to either an HJG group taking HJG extract 7.5 g/day in addition to AChEI or to a control group treated only with AChEI (HJG:33, Control:34). Blood samples were collected before, 3 months, and 6 months after the first drug administration. Comprehensive metabolomic analyses of plasma samples were done by optimized LC-MS/MS and GC-MS/MS methods. The web-based software MetaboAnalyst 5.0 was used for partial least square-discriminant analysis (PLS-DA) to visualize and compare the dynamics of changes in the concentrations of the identified metabolites. Results: The VIP (Variable Importance in Projection) score of the PLS-DA analysis of female participants revealed a significantly higher increase in plasma metabolite levels after HJG administration for 6 months than was seen in the control group. In univariate analysis, the aspartic acid level of female participants showed a significantly higher increase from baseline after HJG administration for 6 months when compared with the control group. Conclusion: Aspartic acid was a major contributor to the difference between the female HJG and control group participants of this study. Several metabolites were shown to be related to the mechanism of HJG effectiveness for mild AD.
RESUMO
Background: Alzheimer's disease (AD) is a progressive neurodegeneration and is the most prevalent form of dementia. Intervention at an early stage is imperative. Although three acetylcholinesterase inhibitors (AChEIs) are currently approved for the treatment of mild AD, they are not sufficiently effective. Novel treatments for mild AD are of utmost importance. Objective: To assess the effectiveness of hachimijiogan (HJG), a traditional Japanese herbal medicine (Kampo), in the treatment of mild AD. Methods: This exploratory, open-label, randomized, multicenter trial enrolled patients with mild AD whose score on the Mini Mental State Examination (MMSE) was over 21points. All participants had been taking the same dosage of AChEI for more than 3 months. The participants were randomly assigned to an HJG group taking HJG extract 7.5 g/day in addition to AChEI or to a control group treated only with AChEI. The primary outcome was the change from baseline to 6 months post treatment initiation on the Alzheimer's Disease Assessment Scale-cognitive component- Japanese version(ADAS-Jcog). The secondary outcomes were change from baseline of the Instrumental Activity of Daily Life (IADL), Apathy scale, and Neuropsychiatric Inventory (NPI) -Q score. Results: Among the 77 enrollees, the data of 69(34 HJG and 35 control)were available for analysis. The difference in the change of ADAS-Jcog from baseline to 6 months of the HJG and control groups was 1.29 (90% Confidence interval (CI), -0.74 to 3.32 p = 0.293). In the subgroup analysis, the differences in the change from baseline to 3 and 6 months for women were 3.70 (90% CI ,0.50 to 6.91, p = 0.059) and 2.90 (90% CI,0.09 to 5.71, p = 0.090), respectively. For patients over 65 years, the difference at 3 months was 2.35 (90%CI, 0.01 to 4.68 p = 0.099). No significant differences were found between the HJG and control groups in IADL score, Apathy scale, or NPI-Q score. Conclusion: Although not conclusive, our data indicate that HJG has an adjuvant effect for acetylcholinesterase inhibitors and that it delays the deterioration of the cognitive dysfunction of mild Altzheimer's disease patients. Clinical Trial Registration: http://clinicaltrials.gov Japan Registry of clinical trials, identifier jRCTs 071190018.
RESUMO
Introduction: We previously reported lower serum 25-hydroxyvitamin D concentrations in patients with Alzheimer's disease (AD), Parkinson's disease (PD) and Multiple system atrophy (MSA) compared to healthy controls (HC), whereas 1,25-di-hydroxyvitamin D levels were solely lower in MSA patients. We investigate serum concentrations of P450 involved in Vitamin D(VD) hydroxylation to clarify the responsible hydroxylase for the low serum concentrations of VD metabolites. Methods: A total of 79 individuals were enrolled including 20 HC, 20 AD, 19 PD and 20 MSA patients. The serum concentrations of P450 involved in VD hydroxylation were assayed by ELISA. The data were analyzed by the nonparametric Kruskal-Wallis test between groups. Results: Though CYP2R1 and CYP27A1 mediate 25-hydroxylation for VD, CYP2R1 is the main hydroxylase, and CYP27A1 is also involved in VD synthesis. CYP2R1 concentrations showed no differences among groups, while lower CYP27A1 concentrations were found in PD (p < 0.05) and MSA (p < 0.005) compared to HC and differences between AD and MSA (p < 0.05), however no differences between PD and MSA. CYP27B1 is the main 1α-hydroxylase for 25-hydroxyvitamin D and showed differences between HC and PD (p < 0.05), between HC and MSA (p < 0.005) and between PD and MSA (p = 0.055). CYP24A1, which inactivate 1,25-di-hydroxyvitamin D, showed no differences among groups. Conclusions: CYP27A1 might affect VD synthesis and cause low 25-hydroxyvitamin D levels in AD, PD and MSA patients. Low 1,25-di-hydroxyvitamin D levels in MSA patients might be caused by impaired feedback mediated by CYP27B1.
RESUMO
BACKGROUND AND PURPOSE: There is sufficient evidence to support vitamin D's noncalcemic effects and the role of vitamin D deficiency in the development of a wide range of neurological disorders. This study aimed to evaluate whether serum 25(OH)D and 1,25(OH) 2 D could be used as biomarkers to differentiate between healthy subjects (HS), multiple system atrophy (MSA) and Parkinson's disease (PD) patients of both genders. METHODS: A total of 107 subjects were included in this study, divided into three groups: 1- HS (n = 61), 2- MSA patients (n = 19), and 3- PD patients (n = 27). The patients were assessed using UMSARS II, UPDRS III, H&Y, MMSE and MoCA rating scales. The levels of 25(OH)D and 1,25(OH) 2 D in serum were determined using the radioimmunoassay technique. RESULTS: The levels of 25(OH)D and 1,25(OH) 2 D in HS were 26.85 +/- 7.62 ng/mL and 53.63 +/- 13.66 pg/mL respectively. 25(OH)D levels were lower in both MSA and PD by 61% and 50%, respectively (P = 0.0001 vs. HS). 1,25(OH) 2 D levels were lower in MSA by 29%(P = 0.001 vs HS). There was a correlation between 25(OH)D and 1,25(OH) 2 D in MSA and PD, but not in HS. 1,25(OH) 2 D regressed with MMSE (ß = 0.476, P = 0.04, R 2 = 0.226) in MSA, and with UPDRS III (ß = -0.432, P = 0.024, R 2 = 0.187) and MoCA (ß = 0.582, P = 0.005,R 2 = 0.279) in PD. 25(OH)D displayed considerable differentiative strength between HS and MSA (Wald = 17.123, OR = 0.586, P = 0.0001; AUC = 0.982, sensitivity and Youden index = 0.882, P = 0.0001) and PD (Wald = 18.552, OR = 0.700, P = 0.0001; AUC = 0.943, sensitivity = 0.889, YI = 0.791, P = 0.0001). 1,25(OH) 2 D distinguished MSA from PD (Wald 16.178, OR = 1.117, P = 0.0001; AUC = 0.868, sensitivity = 0.926, Youden index =0.632, P = 0.0001). H&Y exhibited the highest sensitivity, AUC, and significant distinguishing power between MSA and PD. CONCLUSIONS: Serum 25(OH)D and 1,25(OH) 2 D could be useful biomarkers for MSA and PD. 25(OH)D and H&Y provided the highest sensitivity and group classification characteristics.
RESUMO
Pain is a common non-motor symptom in Parkinson's disease (PD) patients, and the incidence of fluctuating pain may be improved by taking levodopa. There are only a few detailed reports regarding fluctuating pain. In this study, 331 PD patients were classified into three groups: no-pain group (67.4%), non-fluctuating pain group (22.1%), and fluctuating pain group (10.6%). We evaluated patients' background and its impact on the quality of life (QOL) of each group. The pain group exhibited higher levels of depression (p < 0.0001), had a higher frequency of visual hallucinations (p = 0.007), and lower QOL (p < 0.0001) compared with the no-pain group. The fluctuating pain group had a younger onset (p = 0.006), higher Hoehn & Yahr stage (p = 0.018), and higher frequency of wearing-off (p < 0.001) and dyskinesia (p = 0.007) than the other groups. We compared the Parkinson's Disease Questionnaire-8 summary index (PDQ-8 SI) in each pain group to the no-pain group using analysis of variance. As a result, PDQ-8 SI was significantly higher in both the non-fluctuating and fluctuating pain groups (p < 0.0001). Pain is regarded as a non-negligible symptom that affects the QOL of PD patients, and given the unique characteristics, fluctuating pain might be considered as an independent clinical subtype of PD.
RESUMO
A 66-year-old woman with a history of bronchial asthma had shortness of breath and fatigue upon mild exercise. She was diagnosed as congestive heart failure. A blood test showed eosinophilia without the presence of anti-neutrophil cytoplasmic antibody (ANCA), and a myocardial biopsy specimen revealed eosinophilic infiltration in the myocardium. Eosinophilia was improved when she was administered short-term methylprednisolone. After that, she had numbness and pain in her lower limbs with re-elevation of eosinophils. She had dysesthesia and hypalgesia in the distal part of the limbs. Sural nerve biopsy revealed axonal degeneration and thickness of the arterial wall, indicating a diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA). Two courses of steroid pulse therapy were performed, resulting in marked improvement of her sensory symptoms. ANCA-negative EGPA might be associated with myocarditis and peripheral neuropathy. A sufficient immunotherapy should have been considered to prevent rapid progression.
RESUMO
BACKGROUND: Dementia among the Japanese aged 65 years or over population is estimated to approach about 700 million cases by 2025, and a corresponding rapid increase in Alzheimer disease (AD) can also be expected. The ballooning number of dementia patients, including AD, is creating major medical and social challenges. At present, only 3 drugs are recognized for the treatment of mild AD, and these are only used to alleviate symptoms. Although new therapies are needed to treat mild AD, insufficient development of disease-modifying drugs is being done. METHODS/DESIGN: The aim of this exploratory, open standard, treatment-controlled, randomized allocation, multicenter trial is to determine the efficacy of the traditional Japanese Kampo medicine hachimijiogan (HJG) on the cognitive dysfunction of mild AD.Eighty-six patients with AD diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 and as mild AD according to the Mini Mental State Examination (MMSE ≥21) will be included. All will already have been taking the same dose of Donepezil, Galantamine, or Rivastigmine for more than 3 months. The patients will be randomly assigned to receive additional treatment with HJG or to continue mild AD treatment without additional HJG. The primary endpoint is the change from baseline of the Alzheimer's Disease Assessment Scale-cognitive component- Japanese version (ADAS-Jcog). ADAS-Jcog is a useful index for detecting change over time that investigates memory and visuospatial cognition injury from the early stage. The secondary endpoints are the changes from baseline of the Instrumental Activity of Daily Life, Apathy scale, and Nueropsychiatric Inventory scores. In this protocol, we will examine the Geriatric depression scale and do Metabolome analysis as exploratory endpoints. The recruitment period will be from August 2019 to July 2021. DISCUSSION: This is the first trial of Kampo medicine designed to examine the efficacy of HJG for the cognitive dysfunction of patients with mild AD. TRIAL REGISTRATION: This trial was registered on the Japan Registry of Clinical trials on 2 August 2, 2019 (jRCTs 071190018).
Assuntos
Doença de Alzheimer/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Idoso , Cognição/efeitos dos fármacos , Feminino , Humanos , Masculino , Medicina Kampo/métodos , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are two major types of dementia. Due to shared signs and symptoms, accurate diagnosis of these dementia subtypes is a clinical challenge. We assessed the sensitivity and specificity of the combined use of neuropsychological testing and brain imaging data for the differential diagnosis of these conditions. The study population included 77 patients with either AD or DLB. Ala score was calculated from Mini-Mental State Exam subscores, and the cingulate island sign score (CIScore) was obtained from image analysis of brain perfusion single-photon emission computed tomography. Correlation between Ala score and CIScore values was observed in the subgroup of patients aged ≤79 years (r = 0.485, P = 0.002), and the scatter plot revealed that 70% of DLB patients were within the range of cut-off values for DLB. In the group aged ≥80 years, there was poor correlation between the Ala and CIScores (r = 0.285, P = 0.083), the average CIScore exceeded the cut-off value, and the scatter plot showed lower sensitivity, illustrating the challenge of discriminating AD from DLB in an older patient population. The concurrent use of Ala score and CIScore enhanced the specificity and the area under the curve in both subgroups, indicating the improved ability of these tests to aid in the differential diagnosis of AD from DLB. Our findings suggest that the use of these methodologies in routine medical practice may increase the sensitivity and specificity of the diagnosis of dementia subtypes.
Assuntos
Doença de Alzheimer/diagnóstico , Doença por Corpos de Lewy/diagnóstico , Testes Neuropsicológicos , Tomografia Computadorizada de Emissão de Fóton Único , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Humanos , Doença por Corpos de Lewy/diagnóstico por imagem , Masculino , Sensibilidade e EspecificidadeRESUMO
A 64-year-old woman visited our hospital with early-onset dementia and progressive gait disturbance. She had demonstrated a mild communication disorder at the age of ~40 years; however, her psychiatric symptoms at that time were mild and were not accompanied by social problems. At the age of 59, she presented with memory loss, visual hallucinations, and delusions. Over the following five years she developed gait difficulties that gradually deteriorated and suffered frequent falls. On admission, neurological examinations revealed severe pyramidal and extrapyramidal signs of akinetic mutism. MRI of the brain showed cerebral atrophy, enlarged lateral ventricles, thinning of the corpus callosum, and leukoencephalopathy in the frontal-parietal lobes. Additionally, CT revealed a small spotty calcification in the frontal subcortical white matter. Genetic analysis revealed a single-base substitution (c.2330G>A/p.R777Q) in exon 18 of the colony stimulating factor 1 receptor (CSF1R) gene, encoding the CSF1R protein. She was diagnosed with hereditary diffuse leukoencephalopathy with spheroids (HDLS). HDLS is included in the differential diagnosis of early-onset dementia and should be considered in patients with mild personality change and abnormal behavior in the early course of the illness.
Assuntos
Doenças dos Gânglios da Base/etiologia , Delusões/etiologia , Alucinações/etiologia , Leucoencefalopatias/complicações , Transtornos da Memória/etiologia , Neuroglia/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Calcinose , Diagnóstico Diferencial , Feminino , Humanos , Leucoencefalopatias/diagnóstico por imagem , Leucoencefalopatias/genética , Leucoencefalopatias/patologia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Mutação , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/genética , Fatores de Tempo , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Few studies have investigated treatment options for patients with Alzheimer's disease (AD) showing a poor response to oral cholinesterase inhibitors (ChEIs) in Japan. OBJECTIVE: To investigate the efficacy and safety of switching from oral ChEIs to rivastigmine transdermal patch in patients with AD. METHODS: In this multicenter, open-label, phase IV study in outpatient clinics in Japan, patients with mild-moderate AD who had a poor response to or experienced difficulty in continuing donepezil or galantamine were switched to rivastigmine transdermal patch (5 cm2; loaded dose 9 mg, delivery rate 4.6 mg/24 h) with a 1-step titration in week 4 (10 cm2; loaded dose 18 mg, delivery rate 9.5 mg/24 h), which was continued for 4 weeks in the titration period and 16 weeks in a maintenance period. The primary endpoint was the change in Mini-Mental State Examination (MMSE) total score from baseline to week 24. RESULTS: A total of 118 patients were enrolled and switched to rivastigmine, of which 102 completed the 24-week study. The MMSE total score was essentially unchanged during the study, with a least-square mean change (SD) of -0.35 (2.64) at week 24 (p = 0.1750). Exploratory analysis with a mixed-effect model comparing changes in MMSE between the pre- and post-switch periods suggested that switching to rivastigmine prevented a worsening of MMSE. Application site skin reactions/irritations occurred in 30.5% of patients overall, in 22.0% in the 8-week titration period, and in 10.2% in the 16-week maintenance period. CONCLUSION: Within-class switching from an oral ChEI to rivastigmine transdermal patch might be an efficacious and tolerable option for AD patients showing a poor or limited response to a prior oral ChEI.
RESUMO
Objectives: To determine the relevance of Mini-Mental State Examination (MMSE), serum 25-hydroxyvitamin D (25(OH)D3), and 1,25(OH)2D3 concentrations to mild cognitive impairment (MCI) and various stages of Alzheimer's disease (AD). Materials and Methods: The study included 230 participants (>74 years) allocated to three main groups: 1-healthy subjects (HS, n = 61), 2-patients with MCI (n = 61), and 3- patients with Alzheimer's disease (AD) subdivided into three stages: mild (n = 41), moderate (n = 35), and severe AD (n = 32). The cognitive status was evaluated using MMSE. Serum 25 (OH)D3 (ng/ml) and 1,25(OH)2D3 concentrations (pg/ml) were determined by competitive radioimmunoassay. Results: MMSE scores and 25(OH)D3 were decreased in MCI and all stages of the AD in both genders. MMSE variability was due to gender in HS (11%) and to 25(OH)D3 in MCI (15%) and AD (26%). ROC analysis revealed an outstanding property of MMSE in diagnosis of MCI (AUC, 0.906; CI 95%, 0.847-0.965; sensitivity 82%; specificity, 98%) and AD (AUC, 0.997; CI 95%, 0.992-1; sensitivity, 100%; specificity, 98%). 25(OH)D3 exhibited good property in MCI (AUC, 0.765; CI 95%, 0.681-0.849; sensitivity, 90%; specificity, 54%) and an excellent property in diagnosis of AD (AUC, 0.843; CI 95%, 0.782-0.904; sensitivity, 97%; specificity, 79%). Logistic analyses revealed that, in MCI, MMSE could predict (or classify correctly) with 97.6% accuracy (Wald, 15.22, ß, -0.162; SE, 0.554; OR = 0.115:0.039-0.341; p = .0001), whereas 25(OH)D3 with 80% accuracy (Wald, 41,013; ß, -0.213; SE, 0.033; OR = 0.808: 0.757-863; p = .0001). 25(OH)D3 was the only significant predictor for the severe AD and contributed to MMSE variability. Age and gender were significant predictors only in the moderate AD. In patients with MCI, 25(OH)D3 and 1,25(OH)2D3 were correlated men, but in case of the AD, they were correlated in women. Conclusions: MMSE and serum 25(OH)D3 concentrations could be useful biomarkers for prediction and diagnosis of MCI and various stages of the AD. The results support the utility of vitamin D supplementation in AD therapy regimen.
Assuntos
Doença de Alzheimer/sangue , Biomarcadores/sangue , Calcitriol/sangue , Disfunção Cognitiva/sangue , Vitamina D/análogos & derivados , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/classificação , Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/classificação , Disfunção Cognitiva/diagnóstico , Correlação de Dados , Feminino , Humanos , Masculino , Entrevista Psiquiátrica Padronizada , Curva ROC , Sensibilidade e Especificidade , Fatores Sexuais , Vitamina D/sangueRESUMO
Objective Parkinson's disease (PD) is a common, progressive, neurodegenerative disorder. With progression of PD, the wearing-off phenomenon occurs more frequently as a motor complication, decreasing the patient's quality of life. The aim of this study was to investigate the risk factors for the wearing-off phenomenon in Japanese PD patients. Methods All of the study participants were clinically diagnosed as having PD. Each patient was assessed for the wearing-off phenomenon based on the findings of clinical assessments and interviews that were conducted during a single visit. The risk factors for wearing-off were analyzed by univariate and multivariate logistic regression analyses. Results Wearing-off was observed in 101 of the 180 (56.1%) patients who were enrolled in this study. The multivariate logistic regression analysis revealed that the onset of PD at ≥69 years of age (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.05-0.88; p=0.032), female sex (OR, 6.49; 95% CI, 2.34-17.99; p<0.001), catechol-O-methyltransferase (COMT) inhibitor treatment (OR, 19.59; 95% CI, 3.55-108.11; p<0.001) and a high daily levodopa dosage (≥600 mg/day) (OR, 7.69; 95% CI, 1.41-41.84; p=0.018) were independent predictive factors for wearing-off in Japanese PD patients. Conclusion Age at the symptomatic disease onset, female sex, COMT inhibitor treatment, and a high daily levodopa dose were associated with the occurrence of wearing-off in Japanese PD patients. Physicians need to consider the risk factors and carefully choose medications for PD patients to postpone the occurrence of this phenomenon for as long as possible.
Assuntos
Antiparkinsonianos/uso terapêutico , Inibidores de Catecol O-Metiltransferase/uso terapêutico , Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/fisiopatologia , Idade de Início , Idoso , Antiparkinsonianos/administração & dosagem , Inibidores de Catecol O-Metiltransferase/administração & dosagem , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Japão , Levodopa/administração & dosagem , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Fatores de Risco , Fatores SexuaisRESUMO
OBJECTIVES: Multiple system atrophy (MSA) is a progressive neurodegenerative disorder that may be caused in part by oxidative stress. Uric acid (UA) protects neurons in neurodegenerative disorders via antioxidative effects. The aim of this study was to investigate the relationship between the serum UA concentration and disease progression in MSA patients. PATIENTS AND METHODS: A total of 53 Japanese MSA patients were enrolled in this study. The disease progression rate was estimated by the rate of global disability scale change per year. The relationship between the serum UA concentration and disease progression was assessed by Spearman's correlation analysis. Disease progression depending on the UA concentration was also estimated by multivariate logistic regression analysis. RESULTS: MSA patients with the highest serum UA concentration had lower disease progression rates than those with the lowest concentration. Spearman's correlation analysis showed an inverse correlation between the serum UA concentration and disease progression in male patients. Multivariate logistic regression analysis confirmed that the UA concentration was independently related to disease progression only in male patients. CONCLUSION: These results suggest that serum UA may be associated with disease progression in male patients with MSA.
Assuntos
Progressão da Doença , Atrofia de Múltiplos Sistemas/sangue , Ácido Úrico/sangue , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores SexuaisRESUMO
Rivastigmine patches exhibit stable effects when attached once a day, and may reduce Alzheimer's disease (AD) patient's or caregiver's burden. On the other hand, it was reported that adverse events, such as dermal disorder, frequently appeared after the start of rivastigmine administration. We retrospectively investigated medical records in 120 patients with moderate or mild AD in whom rivastigmine administration was started in the Department of Neurology, Fukuoka University Hospital between July 2011 and June 2014 (43 males, 77 females, mean age: 76.9±8.0 years). In 72 patients (60.0%), rivastigmine administration was discontinued within 52 weeks after its start. In 45 of these, it was discontinued before reaching a dose of 18 mg/d which was proven to be effective for AD patients. A primary reason for discontinuation was the appearance or deterioration of adverse events in 64 patients. Of these, 43 complained of dermal disorder, accounting for the highest percentage. To clarify factors influencing the continuous administration of rivastigmine, multivariate analysis was performed in 114 patients meeting criteria. Combination therapy with memantine was extracted as a factor (p=0.008). The results of this study suggest that adherence to combination therapy with rivastigmine and memantine is more favorable than that to monotherapy with rivastigmine.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Memantina/administração & dosagem , Cooperação do Paciente/estatística & dados numéricos , Rivastigmina/administração & dosagem , Rivastigmina/efeitos adversos , Adesivo Transdérmico , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVE: Myasthenia gravis (MG) is an immunological disorder of the neuromuscular junction, characterized by easy fatigability and weakness of the skeletal muscles. However, it has sometimes been reported that heart diseases including cardiomyopathies leading to sudden death have been observed in patients with MG. We studied the prevalence of electrocardiographic (ECG) abnormalities and heart disease in patients newly diagnosed with MG who had not received immunotherapy. METHODS: Fifty-three patients with MG were enrolled in our study. We reviewed the ECG recordings of all patients on admission, and assessed the prevalence of ECG abnormalities and heart diseases associated with MG. RESULTS: Thirty-three (62.2%) patients had ECG abnormalities, including early repolarization (15 patients), negative T waves (9 patients), left ventricular hypertrophy (5 patients), and prolonged QTc (4 patients). A higher frequency of early repolarization was observed in patients with MG compared to healthy subjects. DISCUSSION: ECG abnormalities in patients with MG were more prevalent in our series than in the general population. This may be because of the increasing incidence of MG in the elderly. However, we also observed that younger patients developed severe heart disease, indicating the possibility of other mechanisms, such as the presence of antimyocardial antibodies. Clinicians should be aware of the complications of heart disease in patients with MG, especially during the perioperative period for thymectomy or thymomectomy.
Assuntos
Cardiomiopatias/diagnóstico , Cardiomiopatias/etiologia , Eletrocardiografia , Miastenia Gravis/complicações , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Cardiomiopatias/epidemiologia , Cardiomiopatias/fisiopatologia , Morte Súbita Cardíaca/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores Sexuais , Fumar/efeitos adversos , Adulto JovemRESUMO
AIM: This study aimed to ascertain if performance on the Timed Up and Go (TUG) test is associated with indicators of brain volume and cognitive functions among community-dwelling older adults with normal cognition or mild cognitive impairment. METHODS: Participants were 80 community-dwelling older adults aged 65-89years (44 men, 36 women), including 20 with mild cognitive impairment. Participants completed the TUG and a battery of cognitive assessments, including the Mini-Mental State Examination (MMSE), the Logical Memory I and II (LM-I, LM-II) subtests of the Wechsler Memory Scale-Revised; and the Trail Making Test A and B (TMT-A, TMT-B). Bilateral, right- and left-side medial temporal area atrophy as well as whole gray and white matter indices were determined with the Voxel-based Specific Regional Analysis System for Alzheimer's Disease. We divided participants into three groups based on TUG performance: "better" (≤6.9s); "normal" (7-10s); and "poor" (≥10.1s). RESULTS: Worse TMT-A and TMT-B performance showed significant independent associations with worse TUG performance (P<0.05, P<0.01 for trend, respectively). After adjusting for covariates, severe atrophy of bilateral, right-, and left-side medial temporal areas were significantly independently associated with worse TUG performance (P<0.05 for trend). However, no significant associations were found between MMSE, LM-I, LM-II, whole gray and white matter indices, and TUG performance. CONCLUSIONS: Worse TUG performance is related to poor performance on TMT-A and TMT-B, and is independently associated with severe medial temporal area atrophy in community-dwelling older adults.
Assuntos
Envelhecimento , Cognição , Disfunção Cognitiva/fisiopatologia , Função Executiva , Lobo Temporal/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Atrofia , Estudos Transversais , Feminino , Avaliação Geriátrica/métodos , Humanos , Japão , Modelos Lineares , Imageamento por Ressonância Magnética , Masculino , Lobo Temporal/diagnóstico por imagem , Teste de Sequência AlfanuméricaRESUMO
There have been reports from several countries that hepatitis E virus (HEV) infection is frequently associated with Guillain-Barré syndrome (GBS). This study aimed to determine the frequency of HEV infection associated with GBS in Japanese patients, and to clarify the clinical characteristics of these patients. Sera obtained from 63 patients with GBS or Miller Fisher syndrome (MFS) and 60 control subjects were examined for both HEV-IgM and HEV-IgG. Of the 63 patients, three were positive for both HEV-IgM and elevated hepatic enzymes: Two had GBS, and one had MFS. No control subjects were positive for HEV-IgM. Our study demonstrated that 4.8 % of patients with GBS or MFS from our institution had associated acute HEV infection. There were no clinical differences between GBS with HEV infection and other GBS cases. To our knowledge, this is the first survey in Japan of HEV-associated GBS or MFS.
Assuntos
Síndrome de Guillain-Barré/sangue , Vírus da Hepatite E/imunologia , Hepatite E/sangue , Feminino , Hospitais Universitários/estatística & dados numéricos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Síndrome de Miller Fisher/sangueRESUMO
BACKGROUND: Remitting seronegative symmetrical synovitis with pitting edema syndrome is characterized by symmetrical synovitis with pitting edema in the dorsum of the hands or feet. Most cases of remitting seronegative symmetrical synovitis with pitting edema syndrome are idiopathic, but some are secondary to malignancy, autoimmune disease, or neurodegenerative disorders. Pleural and pericardial effusions are unusual complications in idiopathic remitting seronegative symmetrical synovitis with pitting edema syndrome. CASE PRESENTATION: A 74-year-old Japanese woman presented to our hospital with arthralgia and pitting edema in her feet. She had pain in multiple joints, peripheral edema, and a markedly elevated erythrocyte sedimentation rate. Enhanced computed tomography and laboratory data showed no evidence of malignancy. These findings suggested that she had idiopathic remitting seronegative symmetrical synovitis with pitting edema syndrome. She also developed respiratory distress because of bilateral pleural and pericardial effusions. Laboratory data showed that serum vascular endothelial growth factor and interleukin-6 were significantly elevated. After administration of steroids, her pleural and pericardial effusions decreased and finally disappeared. Furthermore, vascular endothelial growth factor and interleukin-6 decreased when the pleural and pericardial effusions disappeared. CONCLUSIONS: Here we report the case of a patient with idiopathic remitting seronegative symmetrical synovitis with pitting edema syndrome associated with life-threatening complications, including bilateral pleural and pericardial effusions during the course of the illness, which led to respiratory failure and atrial fibrillation. Elevated vascular endothelial growth factor and interleukin-6 may be associated with the cause of pleural and pericardial effusions in idiopathic remitting seronegative symmetrical synovitis with pitting edema syndrome.
Assuntos
Edema/complicações , Derrame Pericárdico/complicações , Derrame Pleural/complicações , Sinovite/complicações , Corticosteroides/uso terapêutico , Idoso , Diagnóstico Diferencial , Edema/diagnóstico , Edema/tratamento farmacológico , Feminino , Humanos , Derrame Pericárdico/diagnóstico , Derrame Pericárdico/tratamento farmacológico , Derrame Pleural/diagnóstico , Derrame Pleural/tratamento farmacológico , Síndrome , Sinovite/diagnóstico , Sinovite/tratamento farmacológicoRESUMO
A 57-year-old man developed migraine at the age of 25 years. Thereafter, he developed depression at the age of 50 years, and was admitted to a psychiatric hospital at the age of 54 years because of deteriorating depression. He returned to his work after receiving treatment for depression; however, he made mistakes several times in his work. He was referred to our hospital for further neurological evaluation. The results of the neurological examination performed on admission were unremarkable. His Mini Mental State Examination (MMSE) score was 24/30, and neuropsycological evaluations revealed executive dysfunction. There was no family history of dementia or cerebral infarction. Magnetic resonance fluid attenuated inversion recovery (MR FLAIR) image of the brain showed hyperintense lesions around the lateral ventricle without involvement in the temporal pole and external capsule. Despite a lack of family history of dementia and cerebral infarction and non-specific brain MRI findings, his history of headache and depression were suggestive of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Therefore, skin biopsy was performed; electron microscopy of the biopsied sample revealed granular osmiophilic material deposits. Genetic analysis of the NOTCH3 gene showed a missense mutation with substitution of R427C in exon 8, i.e., out of the hot-spot, exon 3, and 4. Thus, skin biopsy is a useful tool for diagnosing atypical CADASIL.