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1.
Rinsho Shinkeigaku ; 61(2): 103-108, 2021 Feb 23.
Artigo em Japonês | MEDLINE | ID: mdl-33504747

RESUMO

We retrospectively examined the differences between paramedic triage and final diagnosis in the cases that were transported to our hospital between May 2016 and March 2019. About 30% of the patients with suspected stroke were diagnosed other than stroke. Some of the patients without suspected stroke were diagnosed with large vessel occlusion and were treated with mechanical thrombectomy. The time from arrival at the hospital to treatment was significantly longer in the patients without suspected stroke than with suspected stroke. To achieve a better prehospital care, we need to accept a wide range of stroke mimics, and to continuously feedback the paramedics about the importance of paralysis, cortical symptoms in stroke.

2.
Neurol Sci ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33411202

RESUMO

INTRODUCTION: Idiopathic systemic capillary leak syndrome (ISCLS) is a rare cryptogenic disorder characterized by recurrent hemoconcentration, hypoalbuminemia, edema, and hypotension due to extravascular fluid leakage. This is the first report that details uncommon extensive leukoencephalopathy caused by ISCLS upon a neuropathological investigation. CASE REPORT: A 68-year-old female had recurrent episodes of hemoconcentration, hypoalbuminemia, and generalized edema and was diagnosed with ISCLS. After 9 years, brain magnetic resonance imaging (MRI) incidentally revealed extensive leukoencephalopathy without neurological deficits. Thorough examinations ruled out other disorders, and the cerebral involvement due to ISCLS was finally diagnosed. Three years later, she developed an acute-onset coma and status epilepticus together with hypotension and hemoconcentration, which were compatible with ISCLS recurrence. Electroencephalogram and MRI were correlated with a seizure arising from the left hemisphere. Extensive leukoencephalopathy did not show notable changes for 3 years. Although treatment for ISCLS recurrence temporally improved hemoconcentration and consciousness, consciousness worsened again by marked edema of the left hemisphere, and she died of cerebral herniation. A brain autopsy revealed straggly perivascular plasma leakage around the small vessels of the deep white matter, which supported that the leukoencephalopathy was caused by ISCLS. Widespread myelin pallor and decreased axonal density with sparse astrogliosis and microgliosis were observed in the cerebral white matter and corresponded with a chronic change in the MRI. CONCLUSION: Current radiological and pathological observations revealed that frequent perivascular leakages could cause chronic leukoencephalopathy, were linked with the development of systemic capillary leakage in ISCLS, and provided insights into the mysterious pathophysiology.

3.
Intern Med ; 59(22): 2935-2936, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33191371

RESUMO

Leuconostoc lactis, often found in fermented dairy products, although considered to have a low pathogenic potential, can cause life-threatening infections in immunocompromised hosts. We herein report a 62-year-old man with a history of alcoholic liver cirrhosis, hepatocellular carcinoma, and diabetes mellitus who developed a very rare case of bacterial meningitis caused by this organism. After we administered antibiotics including ampicillin, he recovered completely within two weeks. This gram-positive coccus (GPC) is sensitive to ampicillin but naturally resistant to vancomycin, while its susceptibility to ceftriaxone has not yet been established. In acute GPC meningitis in immunocompromised hosts, Leuconostoc lactis should therefore be considered as a possible pathogen.

4.
Brain Nerve ; 72(10): 1049-1056, 2020 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-33051391

RESUMO

Ninety-six patients were admitted to our hospital during the first wave of the 2020 COVID pandemic. Our hospital, a core hospital in Kobe, was in confusion at the beginning of the pandemic. The following three factors were considered important for preventing the collapse of hospitals during the pandemic based on our experiences: avoidance of contact, prompt and accurate communication, and role-sharing among community medical institutions. Of the 96 patients, 36 had severe cases with several neurological problems: 18 had consciousness disorders, 19 had generalized weakness, 7 had polyneuropathy, and 2 had severe limb weakness. There are several unsolved pathological problems, and neurologists should play important roles in the treatment of patients with COVID.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Hospitalização , Humanos , Neurologistas
5.
J Stroke Cerebrovasc Dis ; 29(12): 105391, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33096496

RESUMO

We report the case of a 27-year-old woman with acute internal carotid artery occlusion long after carotid artery revascularization by vein graft. She presented with sudden unconsciousness and left hemiparesis. Her right carotid artery was revascularized with an ipsilateral internal jugular vein graft during a carotid body tumor resection 10 years ago. Computed tomography angiography revealed a right internal carotid artery terminus occlusion. Intravenous rt-PA and mechanical thrombectomy were performed, resulting in successful recanalization. Her neurological symptoms gradually recovered. When examining the embolic source, carotid ultrasonography for the vein graft showed intimal thickening, some high-echoic plaques, and lumen dilation, but no thrombus was observed. Color Doppler imaging showed laminar flow at the graft. Angiography after thrombectomy also showed pooling of contrast at the vein graft. We suspected that the blood flow stagnation at the vein graft induced thrombus formation; therefore, anticoagulation therapy was initiated. One year later, she was independent without recurrence of stroke, and anticoagulation therapy was replaced with aspirin because she went abroad. However, a carotid ultrasonography exam the following year revealed a huge thrombus at the graft. Anticoagulation therapy was resumed; subsequently, the thrombus decreased. In conclusion, we could monitor the long-term change in the vein graft by ultrasonography. Moreover, anticoagulation therapy was more effective.

6.
Rinsho Shinkeigaku ; 60(11): 758-761, 2020 Nov 27.
Artigo em Japonês | MEDLINE | ID: mdl-33115990

RESUMO

We present the case of an 81-year-old woman who underwent aortic valve replacement and coronary artery bypass surgery by median sternotomy. Following the operation, she experienced distal muscle weakness in her left upper limb and numbness in the medial part of her left forearm and palm. Nerve conduction study revealed low amplitudes of her left ulnar compound muscle action potential (CMAP) and sensory nerve action potential (SNAP), radial CMAP, and medial antebrachial cutaneous SNAP. Needle electromyography showed denervation potentials in the extensor digitorum communis and abductor pollicis brevis. CT and MRI showed a left first rib fracture and a hematoma nearby. Short-T1 inversion recovery image (STIR) showed a high-intensity area in the left root of C8. Based on these findings, we diagnosed the patient with lower trunk brachial plexopathy due to hematoma.

7.
J Stroke Cerebrovasc Dis ; 29(11): 105259, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33066891

RESUMO

BACKGROUND: Muscle mass might be a possible predictor for walking function in patients with stroke; however, evidence is limited. OBJECTIVE: To investigate whether skeletal muscle mass is associated with walking function at discharge during the acute phase. METHODS: In this observational cohort study, we assessed skeletal muscle mass in patients with acute ischemic stroke using the noninvasive and portable multifrequency bio-impedance device. This device can easily be used in bedridden patients. Appendicular skeletal muscle mass was converted to skeletal muscle index (SMI) standardizing by height squared (kg/m2). The primary outcome was walking function assessed by the modified Rankin Scale score at acute phase hospital discharge. Logistic regression analysis was used to determine the association between skeletal muscle mass and walking function. RESULTS: Of the 107 patients enrolled, low SMI (SMI: male <7.0 kg/m2, female <5.7 kg/m2) was identified in 29.9% (19.7% in men, 48.6% in women). Logistic regression analysis showed that low SMI [OR: 4.02, 95% confidence interval (CI): 1.38-11.7, p = 0.001] independently associated with walking function at discharge. Further, patients with mild and moderate severity had significant difficulty in walking when they had low SMI (p = 0.039). CONCLUSIONS: Low skeletal muscle mass at the onset of ischemic stroke is an independent predictor of walking function at discharge during the acute phase. Our findings highlight the importance of detecting skeletal muscle mass in patients with acute ischemic stroke.

8.
Neurol Sci ; 2020 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-32656715

RESUMO

BACKGROUND: Diffusion-weighted imaging (DWI) on magnetic resonance imaging (MRI) shows limited sensitivity in the acute-phase brainstem infarctions, including lateral medullary infarction (LMI), and the detailed characteristics of acute LMI patients with initially negative DWI-MRI findings have not been reported previously. Therefore, we aimed to investigate the differences in the backgrounds or symptoms of acute LMI patients with initially negative findings in standard axial DWI-MRI and those with positive findings. METHODS: In this retrospective cohort study, we collected the data for 35 consecutive acute LMI patients who were hospitalized in our hospital from January 2011 to December 2018. Initial standard axial DWI-MRI was assessed, and the patients were divided into positive and negative groups. The characteristics of the two groups were compared, and the usefulness of additional thin-slice coronal DWI-MRI was also investigated. RESULTS: Nine (26%) acute LMI patients were initially negative on standard axial DWI-MRI. The patients were independently associated with smoking history (78% vs. 23%, p = 0.021) and headache (78% vs. 31%, p = 0.046). Thin-slice coronal DWI-MRI showed positive findings in 50% of the patients with negative findings in standard axial DWI-MRI. All four patients with negative findings in both standard axial and thin-slice coronal DWI-MRI had smoking history and headache. CONCLUSION: Smoking history and headache were associated with initial negative results in standard axial DWI-MRI in acute LMI. Additional thin-slice coronal DWI-MRI was sometimes useful in detecting acute LMI. Follow-up MRI is important for patients showing negative findings in initial DWI-MRI.

9.
Rinsho Shinkeigaku ; 60(4): 268-271, 2020 Apr 24.
Artigo em Japonês | MEDLINE | ID: mdl-32238745

RESUMO

We report a case of a 29-year-old woman with spinal muscular atrophy (SMA) type II who developed severe ketoacidosis after short-term starvation. She was hospitalized with lower respiratory tract infection. Although her symptoms improved after administration of intravenous antibiotic agents, her food intake gradually decreased. On the 7th day of hospitalization, she experienced abdominal pain followed by vomiting, after which she was unable to eat. Approximately 12 h later, she suffered from shock, accompanied with disturbance of consciousness, and she was admitted to the intensive care unit. She was diagnosed with ketoacidosis based on arterial blood gas analyses and urine test results. On receiving continuous infusion of glucose and insulin, her ketoacidosis was rapidly resolved and her symptoms completely recovered by the next day. To prevent the recurrence of ketoacidosis, we provided a diet plan based on indirect calorimetry results. However, ketoacidosis recurred twice, at 12 months and 16 months after discharge, both within 24 h of the onset of the fasting state. In addition to insufficient glycogen storage because of chronic malnutrition, poor gluconeogenesis or poor ketone body consumption due to skeletal muscle atrophy was believed to increase the risk of acute-onset, severe ketoacidosis after short-term starvation. Clinicians must note that patients with SMA are prone to ketoacidosis and that they must be promptly treated.


Assuntos
Cetose/etiologia , Atrofias Musculares Espinais da Infância/complicações , Inanição/complicações , Adulto , Feminino , Humanos , Cetose/diagnóstico , Índice de Gravidade de Doença
10.
Medicine (Baltimore) ; 99(15): e19741, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32282733

RESUMO

INTRODUCTION: Immune-related adverse events (ir-AEs) are increasingly becoming a concern, as immune checkpoint inhibitors (ICIs) are used more frequently. Herein, we present a case of fulminant cytokine release syndrome (CRS) complicated by dermatomyositis after the combination therapy with ICIs. PATIENT CONCERNS: A 70-year-old male developed dermatomyositis during the course of treatment with two ICIs, nivolumab and ipilimumab. He was treated by steroid pulse therapy, but the effect was limited. Afterwards, he had acute-onset high fever, hypotension, respiratory failure, impaired consciousness, renal failure, and coagulation abnormality at the same time. C reactive protein (CRP), creatinine kinase (CK), D-dimer, and ferritin levels were considerably elevated: CRP, 24 mg/dL; CK, 40,500 U/L; D-dimer, 290 µg/mL; ferritin, 329,000 ng/mL. DIAGNOSIS: CRS induced by ICI combination therapy. INTERVENTIONS: Given that high fever and elevated CRP level indicated potential sepsis, an antibiotic was used until the confirmation of negative blood cultures. All the simultaneous acute symptoms were supposed to be CRS. He was admitted to the intensive care unit (ICU), and temporary intubation and hemodialysis were needed. Immunosuppressive therapy was reinforced by mycophenolate mofetil together with steroid, and plasma exchange was performed for the elimination of abnormal proteins. OUTCOMES: The patient's clinical symptoms and laboratory parameters gradually improved and he was discharged from the ICU in a month. CONCLUSION: Fulminant CRS can be induced by ICI combination therapy. As the initial symptoms of CRS resemble sepsis, it is important to consider CRS as a differential diagnosis and to initiate immunosuppressive therapy early when needed. In steroid-resistant cases, early introduction of other immunosuppressive therapy and plasma exchange can be effective.


Assuntos
Terapia Combinada/métodos , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/complicações , Dermatomiosite/etiologia , Idoso , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/uso terapêutico , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores/sangue , Síndrome da Liberação de Citocina/tratamento farmacológico , Dermatomiosite/sangue , Dermatomiosite/patologia , Dermatomiosite/terapia , Diagnóstico Diferencial , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Ipilimumab/administração & dosagem , Ipilimumab/efeitos adversos , Ipilimumab/uso terapêutico , Masculino , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/uso terapêutico , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Nivolumabe/uso terapêutico , Troca Plasmática/métodos , Resultado do Tratamento
11.
J Stroke Cerebrovasc Dis ; 29(6): 104798, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32249205

RESUMO

This is an extremely rare reported case of intravascular large B-cell lymphoma (IVLBCL) presenting with acute hemorrhages and numerous microbleeds. An 80-year-old man presented with consciousness disturbances after convulsion. Computed tomography revealed multiple hemorrhages, and susceptibility-weighted imaging (SWI) demonstrated numerous microbleeds. Brain biopsy showed CD20-positive cells in small vessels; accordingly, IVLBCL was diagnosed. IVLBCL should be considered as a differential diagnosis in multiple cerebral hemorrhages and microbleeds.


Assuntos
Hemorragia Cerebral/etiologia , Hematoma/etiologia , Linfoma de Células B/complicações , Neoplasias Vasculares/complicações , Idoso de 80 Anos ou mais , Antígenos CD20/análise , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores Tumorais/análise , Biópsia , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/patologia , Ciclofosfamida/administração & dosagem , Imagem de Difusão por Ressonância Magnética , Doxorrubicina/administração & dosagem , Hematoma/diagnóstico por imagem , Hematoma/patologia , Humanos , Imuno-Histoquímica , Linfoma de Células B/diagnóstico por imagem , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/patologia , Masculino , Prednisona/administração & dosagem , Rituximab/administração & dosagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Neoplasias Vasculares/diagnóstico por imagem , Neoplasias Vasculares/tratamento farmacológico , Neoplasias Vasculares/patologia , Vincristina/administração & dosagem
12.
J Clin Invest ; 129(12): 5123-5136, 2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31430258

RESUMO

Patients with paroxysmal nocturnal hemoglobinuria (PNH) have a clonal population of blood cells deficient in glycosylphosphatidylinositol-anchored (GPI-anchored) proteins, resulting from a mutation in the X-linked gene PIGA. Here we report on a set of patients in whom PNH results instead from biallelic mutation of PIGT on chromosome 20. These PIGT-PNH patients have clinically typical PNH, but they have in addition prominent autoinflammatory features, including recurrent attacks of aseptic meningitis. In all these patients we find a germ-line point mutation in one PIGT allele, whereas the other PIGT allele is removed by somatic deletion of a 20q region comprising maternally imprinted genes implicated in myeloproliferative syndromes. Unlike in PIGA-PNH cells, GPI is synthesized in PIGT-PNH cells and, since its attachment to proteins is blocked, free GPI is expressed on the cell surface. From studies of patients' leukocytes and of PIGT-KO THP-1 cells we show that, through increased IL-1ß secretion, activation of the lectin pathway of complement and generation of C5b-9 complexes, free GPI is the agent of autoinflammation. Eculizumab treatment abrogates not only intravascular hemolysis, but also autoinflammation. Thus, PIGT-PNH differs from PIGA-PNH both in the mechanism of clonal expansion and in clinical manifestations.


Assuntos
Proteínas do Sistema Complemento/imunologia , Hemoglobinúria Paroxística/imunologia , Inflamassomos/imunologia , Inflamação/imunologia , Proteínas de Membrana/genética , Idoso , Alelos , Anticorpos Monoclonais Humanizados/uso terapêutico , Feminino , Deleção de Genes , Genes Ligados ao Cromossomo X , Alemanha , Glicosilfosfatidilinositóis/metabolismo , Hemólise/efeitos dos fármacos , Humanos , Japão , Leucócitos/imunologia , Masculino , Pessoa de Meia-Idade , Mutação , Mutação Puntual , Células THP-1
13.
Nat Genet ; 51(8): 1215-1221, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31332381

RESUMO

Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disease that is characterized by eosinophilic hyaline intranuclear inclusions in neuronal and somatic cells. The wide range of clinical manifestations in NIID makes ante-mortem diagnosis difficult1-8, but skin biopsy enables its ante-mortem diagnosis9-12. The average onset age is 59.7 years among approximately 140 NIID cases consisting of mostly sporadic and several familial cases. By linkage mapping of a large NIID family with several affected members (Family 1), we identified a 58.1 Mb linked region at 1p22.1-q21.3 with a maximum logarithm of the odds score of 4.21. By long-read sequencing, we identified a GGC repeat expansion in the 5' region of NOTCH2NLC (Notch 2 N-terminal like C) in all affected family members. Furthermore, we found similar expansions in 8 unrelated families with NIID and 40 sporadic NIID cases. We observed abnormal anti-sense transcripts in fibroblasts specifically from patients but not unaffected individuals. This work shows that repeat expansion in human-specific NOTCH2NLC, a gene that evolved by segmental duplication, causes a human disease.


Assuntos
Encéfalo/patologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Desequilíbrio de Ligação , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/patologia , Receptores Notch/genética , Expansão das Repetições de Trinucleotídeos/genética , Adolescente , Adulto , Idoso , Encéfalo/metabolismo , Estudos de Casos e Controles , Feminino , Marcadores Genéticos/genética , Humanos , Corpos de Inclusão Intranuclear/genética , Corpos de Inclusão Intranuclear/patologia , Masculino , Pessoa de Meia-Idade , Linhagem , Receptores Notch/metabolismo , Adulto Jovem
14.
Intern Med ; 58(19): 2871-2874, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31243206

RESUMO

Immune checkpoint inhibitors (ICIs) are promising drugs for various cancers. However, immune activation by ICIs can lead to immune-related adverse events (irAEs). Autoimmune encephalitis is a rare irAE, and its clinical features remain unknown. We herein report two patients with ICI-associated autoimmune encephalitis who, saliently, showed elevated adenosine deaminase (ADA) levels in the cerebrospinal fluid (CSF). This is the first report of increased ADA levels in the CSF of patients with ICI-induced autoimmune encephalitis. Although the mechanism of the ADA increase is poorly understood, elevated ADA in the CSF may be informative in the diagnosis of this rare disorder.


Assuntos
Adenosina Desaminase/líquido cefalorraquidiano , Encefalite/induzido quimicamente , Doença de Hashimoto/induzido quimicamente , Fatores Imunológicos/efeitos adversos , Idoso , Biomarcadores/líquido cefalorraquidiano , Encefalite/líquido cefalorraquidiano , Encefalite/imunologia , Doença de Hashimoto/líquido cefalorraquidiano , Doença de Hashimoto/imunologia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino
15.
Cerebrovasc Dis ; 47(3-4): 127-134, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30965319

RESUMO

BACKGROUND AND PURPOSE: Recent studies have demonstrated that endovascular reperfusion therapy improves clinical outcomes at 90 days after ischemic stroke. However, the effects on long-term outcomes are not well known. We hypothesized that successful reperfusion might be associated with long-term improvement beyond 90 days after endovascular therapy. To assess the long-term effects beyond 90 days, we analyzed the association of successful reperfusion with a temporal change in modified Rankin Scale (mRS) score from 90 days to 1 year after endovascular therapy. METHODS: We retrospectively analyzed a database of consecutive patients with acute ischemic stroke who received endovascular therapy between April 2006 and March 2016 at 4 centers. We compared the incidences of improvement and deterioration in patients with successful reperfusion (i.e., modified thrombolysis in cerebral infarction score of 2b or 3) with those in patients with unsuccessful reperfusion. We defined improvement and deterioration as decrease and increase on the mRS score by 1 point or more from 90 days to 1 year after endovascular therapy respectively. RESULTS: A total of 268 patients were included in the current study. The rate of patients with improvement tended to be higher in patients with successful reperfusion than in patients with unsuccessful reperfusion (20% [34/167 patients] vs. 12% [12/101], p = 0.07). The rate of patients with deterioration was lower in patients with successful reperfusion than in patients with unsuccessful reperfusion (25% [42/167] vs. 42% [42/101], p < 0.01). After adjustment for confounders, successful reperfusion was associated with improvement (adjusted OR 2.65; 95% CI 1.23-5.73; p < 0.05) and deterioration (adjusted OR 0.33; 95% CI 0.18-0.62; p < 0.01), independent of the 90-day mRS score. CONCLUSIONS: Successful reperfusion has further beneficial legacy effects on long-term outcomes beyond 90 days after stroke.


Assuntos
Isquemia Encefálica/terapia , Procedimentos Endovasculares , Reperfusão/métodos , Acidente Vascular Cerebral/terapia , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/fisiopatologia , Bases de Dados Factuais , Avaliação da Deficiência , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Japão , Masculino , Recuperação de Função Fisiológica , Reperfusão/efeitos adversos , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
16.
Seizure ; 65: 101-105, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30659999

RESUMO

PURPOSE: Few studies have assessed the duration of the postictal state after a generalized convulsion (GC) in adults. This study aimed to investigate the postictal duration after a GC and the factors associated with it. METHODS: Patients aged ≥16 years who presented to the emergency department of a community general hospital with an unprovoked GC from January 2015 through December 2016 were evaluated retrospectively. A GC was defined as a bilateral convulsion with apparent impaired consciousness including a generalized tonic-clonic seizure. RESULTS: We evaluated 209 consecutive GCs (median age, 42 years) with the median postictal duration of 0.75 h. The univariate analyses indicated that the median duration of the postictal state was significantly longer: in elderly patients (aged ≥65 years) than in younger patients (aged <65 years) (2 h vs. 0.7 h, p = 0.0005); in patients with higher modified Rankin scale (mRS) scores (≥3) at baseline than in those with lower scores (≤2) (2.5 h vs. 0.7 h, p <0.0001); in patients with longer seizure duration (≥30 min) than in those with shorter duration (55 h vs. 0.7 h, p <0.0001); in patients who were given emergency antiepileptic drugs than in those who were not (16 h vs. 0.6 h, p <0.0001); and in patients who were intubated than in those who were not (63.5 h vs. 0.75 h, p = 0.0009). Multiple linear regression analyses indicated that older age, higher mRS scores at baseline, longer seizure duration, and administration of emergency antiepileptic drugs were independently associated with longer postictal duration. CONCLUSION: Age, baseline functional disability, and seizure duration were factors associated with the duration of the postictal state after a GC.


Assuntos
Ondas Encefálicas/fisiologia , Epilepsia Generalizada/diagnóstico , Epilepsia Generalizada/fisiopatologia , Adolescente , Adulto , Fatores Etários , Anticonvulsivantes , Eletroencefalografia , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
18.
J Diabetes Investig ; 10(2): 466-474, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29975462

RESUMO

AIMS/INTRODUCTION: Diabetic polyneuropathy is one of the most frequent diabetic complications, and impairs patients' quality of life. We evaluated the efficacy and safety of ranirestat (40 mg/day) in patients with diabetic polyneuropathy. MATERIALS AND METHODS: This was a multicenter, placebo-controlled, randomized double-blind, parallel-group, phase III study in which 557 patients were randomly assigned to either the ranirestat or placebo group and assessed for 52 weeks. The co-primary end-points were the changes in tibial motor nerve conduction velocity and total modified Toronto Clinical Neuropathy Score as a measure of clinical symptoms. RESULTS: There was a significant increase in tibial motor nerve conduction velocity in the ranirestat group compared with the placebo group. The difference between groups in the change at last observation was 0.52 m/s (P = 0.021). Increases in nerve conduction velocity in the ranirestat group were found not only in the tibial motor nerves, but also in the median motor nerves, proximal median sensory nerves and distal median sensory nerves. No significant differences in modified Toronto Clinical Neuropathy Score or safety parameters were found between the two groups. CONCLUSIONS: Ranirestat (40 mg/day) was well tolerated and improved nerve conduction velocity. Regarding symptoms and signs, no detectable benefits over the placebo were observed in the ranirestat group during the 52 weeks of treatment.


Assuntos
Aldeído Redutase/antagonistas & inibidores , Neuropatias Diabéticas/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Condução Nervosa/efeitos dos fármacos , Pirazinas/uso terapêutico , Qualidade de Vida , Compostos de Espiro/uso terapêutico , Adulto , Idoso , Neuropatias Diabéticas/epidemiologia , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
19.
JMIR Res Protoc ; 7(12): e12046, 2018 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-30578206

RESUMO

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects the upper and lower motor neurons. Currently, only riluzole and edaravone are approved as drugs to treat ALS and new agents with larger effect sizes are warranted. Exploratory analyses in our previous study (study ID #E0302-J081-761) have suggested that high-dose methylcobalamin (E0302) prolonged the overall survival of ALS patients and suppressed ALS progression in patients with a disease duration of less than 12 months. OBJECTIVE: This clinical trial aims to evaluate the efficacy and safety of E0302 for treatment of ALS patients within one year of onset. METHODS: The Japanese early-stage trial of high-dose methylcobalamin for ALS (JETALS) is a prospective, multicenter, placebo-controlled, double-blind, randomized phase III study conducted at 24 tertiary neurology centers and is funded by the Japan Agency for Medical Research and Development. A total of 128 ALS patients within one year of onset were randomized at a 1:1 ratio to receive intramuscular injection with E0302 50 mg or placebo twice a week for 16 weeks. The primary endpoint is changes in the ALS Functional Rating Scale-Revised (ALSFRS-R) total score at 16 weeks. If patients wish to receive E0302 50 mg after the double-blind administration period, E0302 will be provided to them until March 2020 during the continuous administration period. RESULTS: This study began in October 2017 and is being conducted at 24 participating institutions in Japan. The study is in progress and the patient enrollment period is scheduled to end in August 2019, with follow-up scheduled to end in March 2020. CONCLUSIONS: This study is being performed to revalidate the efficacy and safety of E0302 in patients with early-stage ALS in the first year of symptom onset. If positive results are obtained, the aim is to apply for E0302 approval as a new drug for the treatment of ALS. TRIAL REGISTRATION: ClinicalTrials.gov NCT03548311; https://clinicaltrials.gov/ct2/show/NCT03548311 (Archived by WebCite at http://www.webcitation.org/74Fw3rDzb). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/12046.

20.
J Clin Neurophysiol ; 35(6): 496-503, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30387784

RESUMO

OBJECTIVE: Slow wave with frequency <0.5 Hz are recorded in various situations such as normal sleep, epileptic seizures. However, its clinical significance has not been fully clarified. Although infra-slow activity was recently defined as activity between 0.01 and 0.1 Hz, we focus on the activity recorded with time constant of 2 seconds for practical usage. We defined short "infraslow" activity (SISA) less than 0.5 Hz recorded with time constant of 2 seconds and investigated the occurrence and clinical significance of SISA in acute anoxic encephalopathy. METHODS: This study evaluated the findings of electroencephalography in consecutive 98 comatose patients with acute anoxic encephalopathy after cardiac arrest. We first classified electroencephalography findings conventionally, then investigated SISA by time constant of 2 second and a high-cut filter of 120 Hz, to clarify the relationship between SISA and clinical profiles, especially of clinical outcomes and occurrence of acute posthypoxic myoclonus or acute symptomatic seizures. RESULTS: Short infra-slow activity was found in six patients (6.2%), superimposed on the burst phase of the burst-suppression pattern. All six patients showed acute posthypoxic myoclonus or acute symptomatic seizures (generalized tonic-clonic seizures) and its prognosis was poor. This 100% occurrence of acute posthypoxic myoclonus or acute symptomatic seizures was significantly higher than that in patients without SISA (39.1%; P < 0.05). CONCLUSIONS: Short infra-slow activity in acute anoxic encephalopathy could be associated with acute posthypoxic myoclonus and acute symptomatic seizures. Short infra-slow activity could be a practically feasible biomarker for myoclonus or seizures and poor prognosis in acute anoxic encephalopathy, if it occurs with burst suppression.


Assuntos
Ondas Encefálicas/fisiologia , Hipóxia Encefálica/complicações , Mioclonia/etiologia , Convulsões/etiologia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Coma/fisiopatologia , Eletroencefalografia , Feminino , Análise de Fourier , Humanos , Masculino , Pessoa de Meia-Idade , Mioclonia/diagnóstico , Estudos Retrospectivos , Convulsões/diagnóstico , Fatores de Tempo
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