RESUMO
BACKGROUND AND PURPOSE: Takotsubo cardiomyopathy (TCM) is a serious autonomic complication of Guillain-Barré syndrome (GBS). However, the association between TCM and GBS has not been investigated in detail. We investigated the characteristics of GBS patients with TCM (GBS-TCM). METHODS: Clinical features and anti-ganglioside antibody between the GBS-TCM patients and 62 classical GBS patients without TCM as control patients were compared. RESULTS: Eight GBS-TCM patients were identified, in whom TCM was diagnosed at a mean of 6.5 [range 3-42] days after the onset of GBS. The age at onset of GBS was elder in the GBS-TCM patients than in the control GBS patients (76.5 [56-87] vs. 52 [20-88] years, p < 0.01). Notably, cranial nerve deficits, particularly in the lower cranial nerves, were observed in all GBS-TCM patients (100% vs. 41.9%, p < 0.01). Additionally, the GBS-TCM patients showed a higher GBS disability score at nadir (5 [4-5] vs. 4 [1-5], p < 0.01), and lower Medical Research Council sum scores at admission and nadir (37 [30-44] vs. 48 [12-60] at admission, p < 0.05, and 20 [12-44] vs. 40 [0-60] at nadir, p < 0.05, respectively). Mechanical ventilation was more frequently required in the GBS-TCM patients (62.5% vs. 11.3%, p < 0.01). Three GBS-TCM patients were positive for anti-ganglioside antibodies. CONCLUSIONS: TCM occurred at a relatively early phase of GBS. The characteristics of GBS-TCM were the elder, lower cranial nerve involvements, severe limb weakness, and respiratory failure.
Assuntos
Síndrome de Guillain-Barré , Cardiomiopatia de Takotsubo , Humanos , Cardiomiopatia de Takotsubo/etiologia , Cardiomiopatia de Takotsubo/complicações , Síndrome de Guillain-Barré/complicações , Síndrome de Guillain-Barré/fisiopatologia , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Idoso de 80 Anos ou mais , Adulto , Adulto Jovem , Gangliosídeos/imunologia , Autoanticorpos/sangue , Estudos RetrospectivosRESUMO
Chronic myeloid leukemia (CML) is a clonal hemopoietic stem cell disorder characterized by reciprocal translocation between the long arms of chromosomes 9 and 22 that produces the fusion BCR-ABL1 gene. Major manifestations in CML patients are increased white cell count and splenomegaly. In this case, the patient presented with aseptic meningitis and showed symptoms, such as disorientation, double vision, and neurogenic bladder disorder. Pulse steroid and antibiotic treatment was ineffective for these symptoms; however, the combination therapy with these drugs and dasatinib was very effective. Moreover, our patient had myelopathy that could have been induced by dasatinib after the treatment was started. To our knowledge, this is the first report of meningitis of the paraneoplastic syndrome associated with CML.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Meningite Asséptica , Síndromes Paraneoplásicas , Dasatinibe/uso terapêutico , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Translocação GenéticaRESUMO
OBJECTIVES: The relationship between stroke etiology and clot pathology remains controversial. MATERIALS AND METHODS: We performed histological analysis of clots retrieved from 52 acute ischemic stroke patients using hematoxylin and eosin staining and immunohistochemistry (CD42b and oxidative/hypoxic stress markers). The correlations between clot composition and the stroke etiological group (i.e., cardioembolic, cryptogenic, or large artery atherosclerosis) were assessed. RESULTS: Of the 52 clots analyzed, there were no significant differences in histopathologic composition (e.g., white blood cells, red blood cells, fibrin, and platelets) between the 3 etiological groups (Pâ¯=â¯.92). By contrast, all large artery atherosclerosis clots showed a localized pattern with the oxidative stress marker 4-hydroxyl-2-nonenal (P < .01). From all 52 clots, 4-hydroxyl-2-nonenal expression patterns were localized in 28.8% of clots, diffuse in 57.7% of clots, and no signal in 13.5% of clots. CONCLUSIONS: A localized pattern of 4-hydroxyl-2-nonenal staining may be a novel and effective marker for large artery atherosclerosis (sensitivity 100%, specificity 82%).
Assuntos
Aldeídos/análise , AVC Embólico/etiologia , Trombose Intracraniana/etiologia , AVC Isquêmico/etiologia , Estresse Oxidativo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , AVC Embólico/diagnóstico , AVC Embólico/metabolismo , AVC Embólico/terapia , Feminino , Humanos , Trombose Intracraniana/diagnóstico , Trombose Intracraniana/metabolismo , Trombose Intracraniana/terapia , AVC Isquêmico/diagnóstico , AVC Isquêmico/metabolismo , AVC Isquêmico/terapia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , TrombectomiaRESUMO
Objective: To describe our 1-year experience of the practical use of a mobile communication application by our stroke team. Methods: The mobile Join application (Allm Inc., Tokyo, Japan) was introduced into our stroke team for the purpose of immediate sharing of the patient information. We analyzed the usage situation for 1 year after the introduction of Join, particularly its efficacy in improving the door-to-puncture time (D2P) for thrombectomy cases, and reported our inter-hospital collaboration with the use of Join. Results: The total number of events notified by Join was 337, and they included acute stroke potentially leading to reperfusion therapy in 23% (76 events), head trauma in 14%, brain hemorrhage in 12%, other infarction in 10%, subarachnoid hemorrhage in 8%, and the others in 34%. The information of the patients was shared among the team members before arrival to our hospital in 42% of acute stroke cases. Of 31 patients undergoing mechanical thrombectomy, the median interval between arrival and groin puncture for the directly transported patients with/without pre-hospital information was 77.5 min/87 min, respectively, whereas that of the patients transferred from primary hospitals with/without pre-hospital information was 19 min/71 min (p <0.0001), respectively, demonstrating the efficacy of information sharing in advance through Join in improving the timing of endovascular therapy. For inter-hospital collaboration using the telestroke system, we concluded the partnership agreement with three local primary hospitals by communication via Join at a reasonable cost. Conclusion: Active and effective utilization of the mobile Join application for communication by our stroke team was demonstrated, and it is expected to promote inter-hospital collaboration in stroke treatment.
RESUMO
BACKGROUND: Because dementia is an emerging problem in the world, biochemical markers of cerebrospinal fluid (CSF) and radio-isotopic analyses are helpful for diagnosing Alzheimer's disease (AD). Although blood sample is more feasible and plausible than CSF or radiological biomarkers for screening potential AD, measurements of serum amyloid- ß (Aß), plasma tau, and serum antibodies for Aß1 - 42 are not yet well established. OBJECTIVE: We aimed to identify a new serum biomarker to detect mild cognitive impairment (MCI) and AD in comparison to cognitively healthy control by a new peptidome technology. METHODS: With only 1.5µl of serum, we examined a new target plate "BLOTCHIP®" plus a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) to discriminate control (nâ=â100), MCI (nâ=â60), and AD (nâ=â99). In some subjects, cognitive Mini-Mental State Examination (MMSE) were compared to positron emission tomography (PET) with Pittsburgh compound B (PiB) and the serum probability of dementia (SPD). The mother proteins of candidate serum peptides were examined in autopsied AD brains. RESULTS: Apart from Aß or tau, the present study discovered a new diagnostic 4-peptides-set biomarker for discriminating control, MCI, and AD with 87% of sensitivity and 65% of specificity between control and AD (***pâ<â0.001). MMSE score was well correlated to brain Aß deposition and to SPD of AD. The mother proteins of the four peptides were upregulated for coagulation, complement, and plasticity (three proteins), and was downregulated for anti-inflammation (one protein) in AD brains. CONCLUSION: The present serum biomarker set provides a new, rapid, non-invasive, highly quantitative and low-cost clinical application for dementia screening, and also suggests an alternative pathomechanism of AD for neuroinflammation and neurovascular unit damage.
Assuntos
Doença de Alzheimer/sangue , Biomarcadores/sangue , Disfunção Cognitiva/sangue , Peptídeos/sangue , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/psicologia , Peptídeos beta-Amiloides/sangue , Compostos de Anilina , Disfunção Cognitiva/psicologia , Feminino , Humanos , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Valores de Referência , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Tiazóis , Proteínas tau/sangueRESUMO
Oxidative stress is part of the entire pathological process that underlies the development of Alzheimer's disease (AD), including the mild cognitive impairment (MCI) stage. Twendee X (TwX) is a supplement containing a strong antioxidative mix of eight antioxidants, which has been shown to have a clinical and therapeutic benefit in AD model mice. Here, we conducted a multicenter, randomized, double-blind, and placebo-controlled prospective interventional study to evaluate the efficacy of TwX in mitigating MCI. The primary outcomes were differences in Mini-Mental State Examination (MMSE) and Hasegawa Dementia Scale-revised (HDS-R) scores between baseline and six months for placebo and TwX groups. Seventy-eight subjects with MCI were randomized into placebo (n = 37) and TwX (n = 41) groups. MMSE scores at six months differed significantly between the TwX and placebo groups (p = 0.018), and HDS-R scores for the TwX group exhibited a significant improvement at six months relative to baseline (p = 0.025). The TwX group did not show any change in affective or activities of daily living scores at six months. The present study indicates that strong antioxidative supplement TwX is clinical beneficial for cognitive function in subjects with MCI.
Assuntos
Antioxidantes/uso terapêutico , Ácido Ascórbico/uso terapêutico , Disfunção Cognitiva/tratamento farmacológico , Cistina/uso terapêutico , Suplementos Nutricionais , Glutamina/uso terapêutico , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Cognição , Disfunção Cognitiva/psicologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Testes de Estado Mental e Demência , Estudos Prospectivos , Resultado do TratamentoRESUMO
Werner syndrome (WS) is an autosomal recessive progeroid disorder caused by mutations in the WRN gene (WRN). Most Japanese WS patients are born from a consanguineous marriage with homozygous WRN mutations. We herein report a rare WS patient born from non-consanguineous parents with compound heterozygous WRN mutations with a novel heterogeneous c.1720+1G>A substitution plus the most frequent heterogeneous c.3139-1G>C substitution among Japanese. Although the present case showed clinical characteristics common to previous Japanese WS patients, he had not developed any malignant tumors as of 43 years of age, suggesting that WS patients with this particular genetic mutation have a different phenotype than others.
Assuntos
DNA/genética , Mutação , Helicase da Síndrome de Werner/genética , Síndrome de Werner/genética , Adulto , Análise Mutacional de DNA , Homozigoto , Humanos , Masculino , Linhagem , Fenótipo , Síndrome de Werner/diagnóstico , Helicase da Síndrome de Werner/metabolismoRESUMO
BACKGROUND & OBJECTIVE: Parietal ataxia has been mainly reported as a consequence of acute ischemic stroke, while degenerative parietal ataxia has not been reported. METHODS: We investigated clinical characteristics, neuroimaging data, and genetic analysis of patients with cerebellar ataxia plus parietal atrophy. RESULTS: We identified seven patients, including five patients from two families, with chronic progressive cerebellar ataxia due to degenerative parietal atrophy but not stroke. Age at onset of ataxia was 57.6⯱â¯6.9â¯years. All patients showed chronic progressive cerebellar ataxia with severity of ataxic gaitâ¯>â¯limb ataxiaâ¯>â¯dysarthria. Patients showed no cognitive dysfunction, muscle weakness, or parkinsonism, and only two patients showed mild sensory disturbances. The seven patients showed lateralized limb ataxia with greater contralateral parietal lobe atrophy by magnetic resonance imaging, and hypoperfusion by single photon emission computed tomography, without any abnormal cerebellar pathology (i.e., crossed cerebellar diaschisis). Pathogenic mutations in the microtubule-associated protein tau gene were not found using two single nucleotide polymorphisms. CONCLUSIONS: This is the first description showing unique clinical features of familial and sporadic chronic progressive degenerative parietal ataxia.
Assuntos
Ataxia Cerebelar/diagnóstico por imagem , Ataxia Cerebelar/genética , Lobo Parietal/patologia , Polimorfismo de Nucleotídeo Único/genética , Proteínas tau/genética , Idoso , Apolipoproteínas E/genética , Atrofia/complicações , Ataxia Cerebelar/etiologia , Análise Mutacional de DNA , Saúde da Família , Feminino , Humanos , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Masculino , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Lobo Parietal/diagnóstico por imagem , Índice de Gravidade de Doença , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
A 37-year-old man with anti-muscle-specific tyrosine kinase (MuSK) antibody-positive myasthenia gravis (MG) presented with subacute progressive dysphagia and muscle weakness of the neck and bilateral upper extremities. Conventional immune-suppressive treatments and high-dose intravenous immunoglobulin were ineffective. He then displayed repeated exacerbations and remissions over the course of two years, despite two to four sessions of plasma exchange (PE) every two months. The patient was successfully treated with outpatient periodic weekly blood purification therapy with alternative PE and double-filtration plasmapheresis using an internal shunt. This case report suggests the benefits of blood purification therapy with an internal shunt against anti-MuSK antibody-positive MG.
Assuntos
Assistência Ambulatorial , Autoanticorpos/sangue , Miastenia Gravis/imunologia , Miastenia Gravis/terapia , Troca Plasmática , Plasmaferese , Receptores Proteína Tirosina Quinases/imunologia , Receptores Colinérgicos/imunologia , Adulto , Transtornos de Deglutição/etiologia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Debilidade Muscular/etiologia , Miastenia Gravis/diagnóstico , Tirosina/uso terapêuticoRESUMO
The diagnosis of aortic dissection (AD) is sometimes difficult within the limited time window of recombinant tissue plasminogen activator (tPA) for ischemic stroke (IS). A 60-year-old man developed sudden left hemiparesis due to IS. During tPA infusion, his blood pressure dropped and consciousness declined. After transfer to our hospital, carotid duplex ultrasonography led to a diagnosis of AD. Emergency surgery was postponed because of the risk of hemorrhagic transformation. The patient successfully underwent aortic surgery on day 5 and was discharged with a remarkable improvement in his symptoms. Delayed surgery may avoid hemorrhagic transformation in patients with AD-induced IS who have received tPA.
Assuntos
Dissecção Aórtica/complicações , Dissecção Aórtica/cirurgia , Ataque Isquêmico Transitório/etiologia , Ataque Isquêmico Transitório/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do TratamentoRESUMO
We report a case of a woman with typical dermatomyositis (DM) with skin manifestations, severe myalgia and muscle weakness complicated by interstitial lung disease (ILD) and pneumomediastinum. Pneumomediastinum persisted despite treatment with immunosuppressive therapy (steroids and cyclosporine). After the test for anti-melanoma differentiation-associated gene 5 (MDA5) antibody came out positive, we doubled the cyclosporine dose and her condition improved. Despite typical clinical features of DM, in cases complicated by pneumomediastinum or steroid resistance, measurement of anti-MDA5 antibody may be useful for immunosuppressant dose titration.
Assuntos
Anticorpos/sangue , Dermatomiosite/genética , Dermatomiosite/imunologia , Helicase IFIH1 Induzida por Interferon/imunologia , Idoso , Ciclosporina/administração & dosagem , Ciclosporina/uso terapêutico , Dermatomiosite/sangue , Dermatomiosite/tratamento farmacológico , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêuticoRESUMO
Werner syndrome (WS) is a rare autosomal recessive disorder characterized by a constellation of adult onset phenotypes consistent with an acceleration of intrinsic biological aging. It is caused by pathogenic variants in the WRN gene, which encodes a multifunctional nuclear protein with exonuclease and helicase activities. WRN protein is thought to be involved in optimization of various aspects of DNA metabolism, including DNA repair, recombination, replication, and transcription. In this update, we summarize a total of 83 different WRN mutations, including eight previously unpublished mutations identified by the International Registry of Werner Syndrome (Seattle, WA) and the Japanese Werner Consortium (Chiba, Japan), as well as 75 mutations already reported in the literature. The Seattle International Registry recruits patients from all over the world to investigate genetic causes of a wide variety of progeroid syndromes in order to contribute to the knowledge of basic mechanisms of human aging. Given the unusually high prevalence of WS patients and heterozygous carriers in Japan, the major goal of the Japanese Consortium is to develop effective therapies and to establish management guidelines for WS patients in Japan and elsewhere. This review will also discuss potential translational approaches to this disorder, including those currently under investigation.
Assuntos
Mutação , Helicase da Síndrome de Werner/genética , Síndrome de Werner/genética , Fatores Etários , Animais , Bases de Dados Genéticas , Modelos Animais de Doenças , Éxons , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Geografia , Humanos , Japão , Camundongos , Fenótipo , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Sistema de Registros , Pesquisa Translacional Biomédica , Navegador , Síndrome de Werner/diagnóstico , Síndrome de Werner/epidemiologiaRESUMO
Nuclear pore complexes (NPCs) play an important role in coordinating the transport of proteins and nucleic acids between the nucleus and cytoplasm, and are therefore essential for maintaining normal cellular function and liability. In the present study, we investigated the temporal immunohistochemical distribution of five representative components of NPCs-Ran GTPase-activating protein 1 (RanGap1), glycoprotein-210 (Gp210), nucleoporin 205 (Nup205), nucleoporin 107 (Nup107), and nucleoporin 50 (Nup50)-after 90 min of transient middle cerebral artery occlusion (tMCAO) up to 28 days after the reperfusion in rat brains. Single immunohistochemical analyses showed ring-like stainings along the periphery of the nucleus in sham control brains. After tMCAO, Gp210 and Nup107 immunoreactivity continuously increased from 1 day, and RanGap1, Nup205, and Nup50 increased from 2 days until 28 days, which also displayed progressive precipitations within the nucleus in the peri-ischemic area, while the ischemic core showed scarce expression with collapsed structure. Double immunofluorescent analyses revealed nuclear retention and apparent colocalization of RanGap1 with Nup205, Gp210 with Nup205, and partial colocalization of Nup205 with Nup107; most of the ischemic changes above were similar to those observed in patients with C9orf72-genetic amyotrophic lateral sclerosis. Taken together, these observations suggest that the mislocalization of these nucleoporins may be a common pathogenesis of both ischemic and neurodegenerative disease. © 2016 Wiley Periodicals, Inc.
Assuntos
Isquemia Encefálica/metabolismo , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo , Animais , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , Masculino , Ratos , Ratos WistarAssuntos
Leucoencefalopatia Multifocal Progressiva/complicações , Linfócitos/patologia , Linfoma de Células B/complicações , Idoso , Autopsia , Imagem de Difusão por Ressonância Magnética , Humanos , Leucoencefalopatia Multifocal Progressiva/diagnóstico por imagem , Linfoma de Células B/diagnóstico por imagem , Linfoma de Células B/patologia , MasculinoRESUMO
Clinical data from Japan on the safety and real-world outcomes of alteplase (tPA) thrombolysis in the extended therapeutic window are lacking. The aim of this study was to assess the safety and real-world outcomes of tPA administered within 3-4.5 h of stroke onset. The study comprised consecutive acute ischemic stroke patients (n = 177) admitted across five hospitals between September 2012 and August 2014. Patients received intravenous tPA within <3 or 3-4.5 h of stroke onset. Endovascular therapy was used for tPA-refractory patients. In the 3-4.5 h subgroup (31.6 % of patients), tPA was started 85 min later than the <3 h group (220 vs. 135 min, respectively). However, outcome measures were not significantly different between the <3 and 3-4.5 h subgroups for recanalization rate (67.8 vs. 57.1 %), symptomatic intracerebral hemorrhage (2.5 vs. 3.6 %), modified Rankin Scale score of 0-1 at 3 months (36.0 vs. 23.4 %), and mortality (6.9 vs. 8.3 %). We present data from 2005 to 2012 using a therapeutic window <3 h showing comparable results. tPA following endovascular therapy with recanalization might be superior to tPA only with recanalization (81.0 vs. 59.1 %). Compared with administration within 3 h of ischemic stroke onset, tPA administration within 3-4.5 h of ischemic stroke onset in real-world stroke emergency settings at multiple sites in Japan is as safe and has the same outcomes.
Assuntos
Fibrinolíticos/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Infarto Encefálico/etiologia , Infarto Encefálico/prevenção & controle , Imagem de Difusão por Ressonância Magnética , Relação Dose-Resposta a Droga , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores de TempoRESUMO
We recently experienced 2 young adult patients who developed ischemic stroke after regular intravenous immunoglobulin (IVIg) therapy for agammaglobulinemia with diagnosis of common variable immunodeficiency (CVID) in their childhood. Patient 1 was 26-year-old woman, who developed Wallenberg's syndrome 6 days after the last IVIg therapy, but had no further stroke recurrence with cilostazol later. Patient 2 was 37-year-old man, who developed recurrent cerebral infarction in the territory of bilateral lenticulostriate branches like branch atheromatous disease (BAD) several days after the IVIg therapy. However, he had no further stroke recurrence after bone marrow transplantation (BMT) therapy for his lymphoproliferative disorder. It was suggested that IVIg therapy was associated to these different types of ischemic stroke in our 2 young adult patients with minimal vascular risk factors. Although IVIg therapy is widely used as a relatively safe medication for immunodeficiency disorders or autoimmune diseases, we need to pay more attention to stroke occurrence with regular IVIg therapy.