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1.
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.

2.
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.

3.
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
4.
J Stroke Cerebrovasc Dis ; 29(12): 105343, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33039766

RESUMO

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) outbreak raised concerns over healthcare systems' ability to provide suitable care to stroke patients. In the present study, we examined the provision of stroke care in Kobe City during the COVID-19 epidemic, where some major stroke centers ceased to provide emergency care. METHODS: This was a cross-sectional study. The Kobe Stroke Network surveyed the number of stroke patients admitted to all primary stroke centers (PSCs) in the city between March 1 and May 23, 2020, and between March 3 and May 25, 2019. In addition, online meetings between all PSC directors were held regularly to share information. The survey items included emergency response system characteristics, number of patients with stroke hospitalized within 7 days of onset, administered treatment types (IV rt-PA, mechanical thrombectomy, surgery, and endovascular therapy), and stroke patients with confirmed COVID-19. RESULTS: During the period of interest in 2020, the number of stroke patients hospitalized across 13 PSCs was 813, which was 15.5% lower than that during the same period of 2019 (p = 0.285). The number of patients admitted with cerebral infarction, intracerebral hemorrhage, and subarachnoid hemorrhage decreased by 15.4% (p = 0.245), 16.1% (p = 0.659), and 14.0% (p = 0.715), respectively. However, the rates of mechanical thrombectomy and surgery for intracerebral hemorrhage were slightly increased by 12.1% (p = 0.754) and 5.0% (p = 0.538), respectively. PSCs that ceased to provide emergency care reported a decrease in the number of stroke cases of 65.7% compared with the same period in 2019, while other PSCs reported an increase of 0.8%. No case of a patient with stroke and confirmed COVID-19 was reported during the study period. CONCLUSION: Kobe City was able to maintain operation of its stroke care systems thanks to close cooperation among all city PSCs and a temporal decrease in the total number of stroke cases.

5.
BMC Neurol ; 20(1): 355, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32967629

RESUMO

BACKGROUND: Paraneoplastic cerebellar degeneration (PCD) is a devastating paraneoplastic syndrome that occasionally occurs in patients with Hodgkin lymphoma (HL). Anti-Ma2 is a well-characterized onconeuronal antibody and one of the causes of PCD. There has been only one previous report of anti-Ma2-associated paraneoplastic syndrome as a complication of HL. Here we present a rare case of anti-Ma2-associated PCD in a patient with nodular lymphocyte-predominant HL (NLPHL). CASE PRESENTATION: A 77-year-old man with a 3-month history of gait instability and a 2-month history of oscillopsia was referred to our hospital for further investigation. On examination, his cognition was normal. He had nystagmus in all directions of gaze; specifically, he had horizontal and rotatory nystagmus in the primary position, downbeat nystagmus after right, left, and up gaze, and upbeat nystagmus after down gaze. Although his limb ataxia was mild, his trunk ataxia was so pronounced that he was unable to walk without support. We strongly suspected paraneoplastic syndrome and tested for neuronal autoantibodies. The anti-Ma2 antibody was strongly positive in the blood and cerebrospinal fluid but other antineuronal autoantibodies were negative. Computed tomography showed an enlarged lymph node in the right axilla but no masses. Biopsy confirmed a diagnosis of NLPHL. The NLPHL cells stained with anti-Ma-2 antibody in the cytoplasm, suggesting these abnormal cells contained protein that was cross-reactive with Ma-2. CONCLUSIONS: To the best of our knowledge, this is the first case of anti-Ma2-associated PCD in a patient with NLPHL that was confirmed using immunostaining of the lymph node tissue with anti-Ma2 antibody. Our case confirms an association between anti-Ma2-associated PCD and NLPHL.


Assuntos
Antígenos de Neoplasias/imunologia , Doença de Hodgkin/complicações , Proteínas do Tecido Nervoso/imunologia , Degeneração Paraneoplásica Cerebelar/etiologia , Degeneração Paraneoplásica Cerebelar/imunologia , Idoso , Autoanticorpos/sangue , Autoanticorpos/imunologia , Autoantígenos/imunologia , Doença de Hodgkin/imunologia , Humanos , Masculino , Degeneração Paraneoplásica Cerebelar/diagnóstico , Tomografia Computadorizada por Raios X
6.
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
7.
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
8.
BMC Neurol ; 19(1): 252, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31653203

RESUMO

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a demyelinating disorder caused by JC virus (JCV). Although detecting JCV DNA in the cerebrospinal fluid (CSF) by real-time polymerase chain reaction (PCR) is useful, diagnosis is difficult when JCV concentrations are low. We therefore aimed to lower the detection limit of real-time PCR testing by enriching JCV in the CSF via ultrafiltration. METHODS: Virus suspensions and CSF specimens from 20 untreated patients with suspected PML were collected and total DNAs were extracted. The JCV large T gene was detected by quantitative real-time PCR under condition with and without prior centrifugal ultrafiltration. RESULTS: The JCV DNA was reliably detected to a lower limit of 10 copies/mL of virus suspension by real-time PCR with ultrafiltration. When using this method, the quantity of JCV DNA per PCR reaction increased 3.2- to 8.7-fold compared with the standard procedure. Seven patients were positive for JCV when using the standard procedure, and an additional patient was positive when using ultrafiltration. All JCV-positive patients had neurological features and magnetic resonance imaging findings compatible with PML. CONCLUSIONS: The detection limit of JCV DNA by real-time PCR can be lowered by viral enrichment using ultrafiltration. Our simple protocol offers a valuable tool for PML diagnosis when extremely low copy numbers of JCV are released into the CSF or when brain biopsy is not feasible.


Assuntos
DNA Viral/líquido cefalorraquidiano , Vírus JC/isolamento & purificação , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Reação em Cadeia da Polimerase em Tempo Real/métodos , Ultrafiltração/métodos , Adulto , Feminino , Humanos , Leucoencefalopatia Multifocal Progressiva/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade
9.
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
10.
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
11.
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
12.
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
14.
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
15.
BMJ Case Rep ; 20182018 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-30262533

RESUMO

We report the case of a patient with PIGT mutations who experienced recurrent aseptic meningitis 121 times over 16 years before developing paroxysmal nocturnal haemoglobinuria (PNH). Each episode was preceded by urticaria and arthralgia. After developing PNH, haemolysis occurred prior to meningitis. Flow cytometry revealed deficiency of the glycophosphatidylinositol (GPI)-anchored complement regulatory proteins, CD59 and CD55, and he was diagnosed with PNH. All the symptoms disappeared on administering eculizumab, an anti-C5 antibody. We did not detect mutation in PIGA, which is regarded as the cause of PNH. However, we detected a germ-line mutation and a somatic microdeletion in chromosome 20q including PIGT; PIGT is essential for transferring GPI anchor to the precursors of CD59 and CD55, which play important roles in complement regulation. Loss of these proteins leads to complement overactivation, causing inflammatory symptoms, including recurrent meningitis. PIGT mutations should be considered a novel pathogenesis of recurrent meningitis of unknown aetiology.


Assuntos
Aciltransferases/genética , Anticorpos Monoclonais Humanizados/uso terapêutico , Hemoglobinúria Paroxística , Meningite Asséptica/etiologia , Lesão Renal Aguda/etiologia , Idoso , Citometria de Fluxo , Mutação em Linhagem Germinativa , Glicosilfosfatidilinositóis/biossíntese , Hemoglobinúria Paroxística/complicações , Hemoglobinúria Paroxística/diagnóstico , Hemoglobinúria Paroxística/tratamento farmacológico , Hemoglobinúria Paroxística/genética , Humanos , Masculino , Meningite Asséptica/tratamento farmacológico
16.
Intern Med ; 57(24): 3659-3662, 2018 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-30101927

RESUMO

Loss of consciousness occurs in post-hyperventilation apnea, but its pathophysiology remains unclear. We herein report a patient with post-hyperventilation apnea showing spindle activity on electroencephalogram (EEG). The patient was alert and breathing spontaneously before the hyperventilation test, but loss of consciousness and apnea with spindle activity on EEG occurred when the end-tidal CO2 decreased during the hyperventilation test. She recovered consciousness and spontaneous breathing with the disappearance of the spindle activity on EEG when the end-tidal CO2 increased after the hyperventilation test. The loss of consciousness during post-hyperventilation apnea might be due to the focal involvement of the ascending-activating mesodiencephalic reticular formation.


Assuntos
Apneia/etiologia , Eletroencefalografia , Hiperventilação/complicações , Hiperventilação/fisiopatologia , Inconsciência/etiologia , Adulto , Apneia/fisiopatologia , Feminino , Humanos , Inconsciência/fisiopatologia
17.
Intern Med ; 57(18): 2727-2734, 2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-29709947

RESUMO

A 37-year-old woman with systemic lupus erythematosus presented with gait disturbance and cognitive dysfunction. Brain magnetic resonance imaging (MRI) revealed small, punctate, T2-/fluid-attenuated inversion recovery-hyperintense and T1-hypointense lesions without gadolinium enhancement, which is atypical for progressive multifocal leukoencephalopathy (PML). On a pathological examination of biopsied brain tissues, JC virus-infected cells were hardly detected via immunohistochemistry but were certainly detected via in situ hybridization, conclusively verifying the PML diagnosis. After tapering off the immunosuppressant and mefloquine administration, the MRI findings revealed gradual improvement, and she has been stable for over 18 months. A punctate MRI pattern is not specific to natalizumab-associated PML but may be a ubiquitous early sign useful for the early diagnosis of PML.


Assuntos
Leucoencefalopatia Multifocal Progressiva/diagnóstico por imagem , Leucoencefalopatia Multifocal Progressiva/patologia , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/patologia , Imagem por Ressonância Magnética , Adulto , Biópsia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/virologia , Feminino , Humanos , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Imunossupressores , Hibridização In Situ , Vírus JC/isolamento & purificação , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Mefloquina/efeitos adversos , Mefloquina/uso terapêutico , Natalizumab/efeitos adversos , Natalizumab/uso terapêutico
18.
Lancet Neurol ; 17(6): 519-529, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29685815

RESUMO

BACKGROUND: Despite the introduction of plasmapheresis and immunoglobulin therapy, many patients with Guillain-Barré syndrome still have an incomplete recovery. Evidence from pathogenesis studies suggests the involvement of complement-mediated peripheral nerve damage. We aimed to investigate the safety and efficacy of eculizumab, a humanised monoclonal antibody against the complement protein C5, in patients with severe Guillain-Barré syndrome. METHODS: This study was a 24 week, multicentre, double-blind, placebo-controlled, randomised phase 2 trial done at 13 hospitals in Japan. Eligible patients with Guillain-Barré syndrome were aged 18 years or older and could not walk independently (Guillain-Barré syndrome functional grade 3-5). Patients were randomly assigned (2:1) to receive 4 weeks of intravenous immunoglobulin plus either eculizumab (900 mg) or placebo; randomisation was done via a computer-generated process and web response system with minimisation for functional grade and age. The study had a parallel non-comparative single-arm outcome measure. The primary outcomes were efficacy (the proportion of patients with restored ability to walk independently [functional grade ≤2] at week 4) in the eculizumab group and safety in the full analysis set. For the efficacy endpoint, we predefined a response rate threshold of the lower 90% CI boundary exceeding 50%. This trial is registered with ClinicalTrials.gov, number, NCT02493725. FINDINGS: Between Aug 10, 2015, and April 21, 2016, 34 patients were assigned to receive either eculizumab (n=23) or placebo (n=11). At week 4, the proportion of the patients able to walk independently (functional grade ≤2) was 61% (90% CI 42-78; n=14) in the eculizumab group, and 45% (20-73; n=5) in the placebo group. Adverse events occurred in all 34 patients. Three patients had serious adverse events: two in the eculizumab group (anaphylaxis in one patient and intracranial haemorrhage and abscess in another patient) and one in the placebo group (depression). The possibility that anaphylaxis and intracranial abscess were related to eculizumab could not be excluded. No deaths or meningococcal infections occurred. INTERPRETATION: The primary outcome measure did not reach the predefined response rate. However, because this is a small study without statistical comparison with the placebo group, the efficacy and safety of eculizumab could be investigated in larger, randomised controlled trials. FUNDING: The Japan Agency for Medical Research and Development, Ministry of Health, Labor and Welfare, and Alexion Pharmaceuticals.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome de Guillain-Barré/tratamento farmacológico , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Atividade Motora , Recuperação de Função Fisiológica , Resultado do Tratamento
20.
Rinsho Shinkeigaku ; 57(12): 785-787, 2017 Dec 27.
Artigo em Japonês | MEDLINE | ID: mdl-29187691

RESUMO

A 67-year-old man presented with hoarseness, dysarthria and deviation of the tongue to the left side the day after the open-heart operation under general anesthesia. Brain MRI demonstrated no causal lesion, and laryngoscope showed left vocal cord abductor palsy, so we diagnosed him with Tapia's syndrome (i.e., concomitant paralysis of the left recurrent and hypoglossal nerve). His neurological symptoms recovered gradually and improved completely four months after the onset. Tapia's syndrome is a rare condition caused by the extra cranial lesion of the recurrent laryngeal branch of the vagus nerve and the hypoglossal nerve, and mostly described as a complication of tracheal intubation. In this case, transesophageal echo probe has been held in the left side of the pharynx, so compression to the posterior wall of pharynx by the probe resulted in this condition, and to the best of our knowledge, this is the first report of Tapia's syndrome due to transesophageal echocardiography during an open-heart operation. This rare syndrome should be considered as a differential diagnosis of dysarthria and tongue deviation after a procedure associated with compression to the pharynx.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Ecocardiografia Transesofagiana/efeitos adversos , Doenças do Nervo Hipoglosso/etiologia , Complicações Intraoperatórias/etiologia , Paralisia das Pregas Vocais/etiologia , Idoso , Diagnóstico Diferencial , Disartria/etiologia , Ecocardiografia Transesofagiana/instrumentação , Humanos , Doenças do Nervo Hipoglosso/diagnóstico , Masculino , Síndrome , Paralisia das Pregas Vocais/diagnóstico
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