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1.
Intern Med ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38897956

RESUMO

Huntington's disease (HD) is a dominantly inherited neurological disorder characterized by chorea, psychiatric symptoms, and cognitive decline but typically lacks muscular atrophy and weakness. We herein report a case of genetically confirmed HD showing progressive systemic weakness with findings of upper and lower motor neuron involvement due to amyotrophic lateral sclerosis (ALS). The current patient and the previously reported cases with complications of HD and ALS indicate that cytosine-adenine-guanine (CAG) repeat expansion in the huntingtin gene might have a pathogenic role in causing the two neurological disorders.

2.
Intern Med ; 62(23): 3545-3548, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37062747

RESUMO

We herein report a case of anti-gamma aminobutyric acid type A receptor antibody-associated encephalitis (anti-GABAA-RE) with progressive aphasia and generalized tonic-clonic seizures. Cerebral magnetic resonance imaging (MRI) showed cortical brain lesions coupled with hypermetabolism on fluorodeoxyglucose-positron emission tomography. After two courses of methylprednisolone pulse therapy, improvements in neurological symptoms without sequelae and the total disappearance of MRI lesions were observed. Upon encountering patients with refractory status epilepticus, multifocal cerebral MRI lesions, and suspected autoimmune encephalitis, especially in cases with thymoma, it would be prudent to suspect anti-GABAA-RE and consider the evaluation of anti-GABAA receptor antibody and methylprednisolone pulse therapy.


Assuntos
Encefalite , Neoplasias do Timo , Humanos , Encéfalo/patologia , Receptores de GABA-A/metabolismo , Encefalite/diagnóstico por imagem , Encefalite/tratamento farmacológico , Imageamento por Ressonância Magnética/métodos , Anticorpos , Neoplasias do Timo/complicações , Metilprednisolona/uso terapêutico , Glucose/metabolismo , Autoanticorpos
3.
J Neurol Sci ; 448: 120618, 2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-37001413

RESUMO

Neuronal intranuclear inclusion disease (NIID) is a clinically complex neurological disorder that appears sporadically or autosomally. Expansions of intronic GGC trinucleotide repeats in the NOTCH2 N-terminal-like C (NOTCH2NLC) gene cause NIID. In this study, to clarify the clinical characteristics useful for the differential diagnosis of NIID, clinical data of neurological examination, neuroimaging, and nerve conduction studies of six NIID patients diagnosed by pathological or genetic investigations were analyzed. Clinically useful characteristics for diagnosing NIID include general hyporeflexia, episodic disturbance of consciousness, sensory disturbance, miosis, and dementia. Furthermore, neuroimaging findings, such as leukoencephalopathy in T2-weighted magnetic resonance imaging and a linear high intensity of subcortical U-fibers in diffusion-weighted imaging (DWI), as well as decreased motor nerve conduction velocity, are especially important biomarkers for NIID. However, it is necessary to remember that these features may not always be present, as shown in one of the cases who did not have a DWI abnormality in this study. This study also investigated whether expanded GGC repeats were translated into polyglycine. Immunohistochemical analysis using a custom antibody raised against putative C-terminal polypeptides followed by polyglycine of uN2CpolyG revealed that polyglycines were localized in the intranuclear inclusions in skin biopsy specimens from all six patients, suggesting its involvement in the pathogenesis of NIID.


Assuntos
Corpos de Inclusão Intranuclear , Doenças Neurodegenerativas , Humanos , Corpos de Inclusão Intranuclear/patologia , Doenças Neurodegenerativas/diagnóstico por imagem , Doenças Neurodegenerativas/genética , Peptídeos
4.
J Neurol Sci ; 438: 120281, 2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-35609364

RESUMO

To elucidate clinically useful imaging characteristics of multiple system atrophy with predominant cerebellar ataxia (MSA-C) at the initial stage showing pure cerebellar ataxia but unfilling consensus criteria (MSA-pc), clinical and neuroradiological analyses on cerebral MRI and single-photon emission computed tomography (SPECT) for measuring regional cerebral blood flow (rCBF) were performed. Seven MSA-pc patients meeting the above condition at an initial evaluation were identified, and all the MSA-pc patients later developed autonomic dysfunction and finally fulfilled the criteria for probable or possible category of MSA-C. For comparison, two patients with spinocerebellar ataxia type 6 and three patients with idiopathic cerebellar ataxia who did not exhibit autonomic dysfunction for more than three years were enrolled in this study (non-MSA-pc). As non-ataxic controls without cerebellar involvement, seven patients with Parkinson's disease were also enrolled. As a result, MRI analysis clarified a smaller pontine area and significant laterality of middle cerebellar peduncle (MCP) width in MSA-pc in comparison to non-MSA-pc and controls. SPECT analysis revealed that pontine rCBF was reduced even at the initial stage of MSA-pc. Moreover, the laterality of cerebellar rCBF values and the laterality of MCP width in MSA-pc patients exhibited a significant positive correlation, indicating anatomical and functional laterality of afferent projections to cerebellum is a characteristic finding for MSA-pc. These neuroimaging characteristics could be clinically useful to consider the possibility of the criteria-unfulfilled MSA and promote an earlier intervention after obtaining a diagnosis of probable MSA-C.


Assuntos
Ataxia Cerebelar , Pedúnculo Cerebelar Médio , Atrofia de Múltiplos Sistemas , Ataxia Cerebelar/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Lateralidade Funcional , Humanos , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada de Emissão de Fóton Único/métodos
5.
Clin Neurol Neurosurg ; 212: 107070, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34894573

RESUMO

We report a case of a 59-year-old man with hypertrophic pachymeningitis (HP), initially presenting as a tumefactive lesion that disappeared spontaneously. He developed headache and left abducens nerve palsy 2 years before admission, and cerebral magnetic resonance imaging (MRI) revealed a round mass lesion. Meningioma was initially considered, but the lesion disappeared spontaneously along with the symptoms. However, 6 months before admission, left abducens nerve palsy reappeared. Repeated MRI revealed multiple intracranial tumefactive lesions. HP was diagnosed based on the pathological analysis of the biopsied specimen. HP can appear as a vanishing tumor, and pathological evaluation is essential for a precise diagnosis. If spontaneous disappearance of tumefactive intracranial lesions is encountered, the possibility of HP should be considered.


Assuntos
Dura-Máter/diagnóstico por imagem , Meningite/diagnóstico , Doenças Neuroinflamatórias/diagnóstico , Humanos , Hipertrofia/diagnóstico , Masculino , Pessoa de Meia-Idade
6.
Front Neurol ; 12: 645625, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305778

RESUMO

In Alzheimer's disease, the apolipoprotein E gene (APOE) ε2 allele is a protective genetic factor, whereas the APOE ε4 allele is a genetic risk factor. However, both the APOE ε2 and the APOE ε4 alleles are genetic risk factors for lobar intracerebral hemorrhage. The reasons for the high prevalence of lobar intracerebral hemorrhage and the low prevalence of Alzheimer's disease with the APOE ε2 allele remains unknown. Here, we describe the case of a 79-year-old Japanese female with Alzheimer's disease, homozygous for the APOE ε2 allele. This patient presented with recurrent lobar hemorrhages and multiple cortical superficial siderosis. The findings on the 11C-labeled Pittsburgh Compound B-positron emission tomography (PET) were characteristic of Alzheimer's disease. 18F-THK5351 PET revealed that the accumulation of 18F-THK 5351 in the right pyramidal tract at the pontine level, the cerebral peduncle of the midbrain, and the internal capsule, reflecting the lesions of the previous lobar intracerebral hemorrhage in the right frontal lobe. Moreover, 18F-THK5351 accumulated in the bilateral globus pallidum, amygdala, caudate nuclei, and the substantia nigra of the midbrain, which were probably off-target reaction, by binding to monoamine oxidase B (MAO-B). 18F-THK5351 were also detected in the periphery of prior lobar hemorrhages and a cortical subarachnoid hemorrhage, as well as in some, but not all, areas affected by cortical siderosis. Besides, 18F-THK5351 retentions were observed in the bilateral medial temporal cortices and several cortical areas without cerebral amyloid angiopathy or prior hemorrhages, possibly where tau might accumulate. This is the first report of a patient with Alzheimer's disease, carrying homozygous APOE ε2 allele and presenting with recurrent lobar hemorrhages, multiple cortical superficial siderosis, and immunohistochemically vascular amyloid ß. The 18F-THK5351 PET findings suggested MAO-B concentrated regions, astroglial activation, Waller degeneration of the pyramidal tract, neuroinflammation due to CAA related hemorrhages, and possible tau accumulation.

7.
Front Neurol ; 12: 543866, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33889121

RESUMO

Lobar cerebral microbleeds (CMBs) in Alzheimer's disease (AD) are associated with cerebral amyloid angiopathy (CAA) due to vascular amyloid beta (Aß) deposits. However, the relationship between lobar CMBs and clinical subtypes of AD remains unknown. Here, we enrolled patients with early- and late-onset amnestic dominant AD, logopenic variant of primary progressive aphasia (lvPPA) and posterior cortical atrophy (PCA) who were compatible with the AD criteria. We then examined the levels of cerebrospinal fluid (CSF) biomarkers [Aß1-42, Aß1-40, Aß1-38, phosphorylated tau 181 (P-Tau), total tau (T-Tau), neurofilament light chain (NFL), and chitinase 3-like 1 protein (YKL-40)], analyzed the number and localization of CMBs, and measured the cerebral blood flow (CBF) volume by 99mTc-ethyl cysteinate dimer single photon emission computerized tomography (99mTc ECD-SPECT), as well as the mean cortical standard uptake value ratio by 11C-labeled Pittsburgh Compound B-positron emission tomography (11C PiB-PET). Lobar CMBs in lvPPA were distributed in the temporal, frontal, and parietal lobes with the left side predominance, while the CBF volume in lvPPA significantly decreased in the left temporal area, where the number of lobar CMBs and the CBF volumes showed a significant inversely correlation. The CSF levels of NFL in lvPPA were significantly higher compared to the other AD subtypes and non-demented subjects. The numbers of lobar CMBs significantly increased the CSF levels of NFL in the total AD patients, additionally, among AD subtypes, the CSF levels of NFL in lvPPA predominantly were higher by increasing number of lobar CMBs. On the other hand, the CSF levels of Aß1-38, Aß1-40, Aß1-42, P-Tau, and T-Tau were lower by increasing number of lobar CMBs in the total AD patients. These findings may suggest that aberrant brain hypoperfusion in lvPPA was derived from the brain atrophy due to neurodegeneration, and possibly may involve the aberrant microcirculation causing by lobar CMBs and cerebrovascular injuries, with the left side dominance, consequently leading to a clinical phenotype of logopenic variant.

8.
JAMA Neurol ; 78(7): 853-863, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34047774

RESUMO

Importance: Repeat expansion of CGG in LRP12 has been identified as the causative variation of oculopharyngodistal myopathy (OPDM). However, to our knowledge, the clinicopathologic features of OPDM with CGG repeat expansion in LRP12 (hereafter referred to as OPDM_LRP12) remain unknown. Objective: To identify and characterize the clinicopathologic features of patients with OPDM_LRP12. Design, Setting, and Participants: This case series included 208 patients with a clinical or clinicopathologic diagnosis of oculopharyngeal muscular dystrophy (OPDM) from January 1, 1978, to December 31, 2020. Patients with GCN repeat expansions in PABPN1 were excluded from the study. Repeat expansions of CGG in LRP12 were screened by repeat primed polymerase chain reaction and/or Southern blot. Main Outcomes and Measures: Clinical information, muscle imaging data obtained by either computed tomography or magnetic resonance imaging, and muscle pathologic characteristics. Results: Sixty-five Japanese patients with OPDM (40 men [62%]; mean [SD] age at onset, 41.0 [10.1] years) from 59 families with CGG repeat expansions in LRP12 were identified. This represents the most common OPDM subtype among all patients in Japan with genetically diagnosed OPDM. The expansions ranged from 85 to 289 repeats. A negative correlation was observed between the repeat size and the age at onset (r2 = 0.188, P = .001). The most common initial symptoms were ptosis and muscle weakness, present in 24 patients (37%). Limb muscle weakness was predominantly distal in 53 of 64 patients (83%), but 2 of 64 patients (3%) had predominantly proximal muscle weakness. Ptosis was observed in 62 of 64 patients (97%), and dysphagia or dysarthria was observed in 63 of 64 patients (98%). A total of 21 of 64 patients (33%) had asymmetric muscle weakness. Aspiration pneumonia was seen in 11 of 64 patients (17%), and 5 of 64 patients (8%) required mechanical ventilation. Seven of 64 patients (11%) developed cardiac abnormalities, and 5 of 64 patients (8%) developed neurologic abnormalities. Asymmetric muscle involvement was detected on computed tomography scans in 6 of 27 patients (22%) and on magnetic resonance imaging scans in 4 of 15 patients (27%), with the soleus and the medial head of the gastrocnemius being the worst affected. All 42 muscle biopsy samples showed rimmed vacuoles. Intranuclear tubulofilamentous inclusions were observed in only 1 of 5 patients. Conclusions and Relevance: This study suggests that OPDM_LRP12 is the most frequent OPDM subtype in Japan and is characterized by oculopharyngeal weakness, distal myopathy that especially affects the soleus and gastrocnemius muscles, and rimmed vacuoles in muscle biopsy.


Assuntos
Expansão das Repetições de DNA , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Distrofias Musculares/diagnóstico , Adolescente , Adulto , Feminino , Humanos , Japão , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Debilidade Muscular , Músculo Esquelético/patologia , Linhagem , Adulto Jovem
9.
J Clin Neurosci ; 72: 244-251, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31839382

RESUMO

In clinical settings, it is often difficult to distinguish inclusion body myositis (IBM) from other neuromuscular diseases. In order to clarify clinically useful characteristics for making the differential diagnosis of IBM, we performed clinical, epidemiological, and neuroimaging analyses in patients with various types of neuromuscular disorders. We enrolled 333 patients with myopathy and 12 patients with amyotrophic lateral sclerosis (ALS) who had been hospitalized in our department from January 1, 1979, to December 31, 2018. Among them, 18 patients with IBM, 16 patients with polymyositis (PM), and 12 patients with ALS who showed equivalent severity of muscle weakness in their lower limbs underwent the quantitative neuroimaging analysis using lower limb CT and clinical assessment. Patients with IBM exhibited significantly greater muscular degeneration in the rectus femoris, vastus, sartorius, adductor, anterior calf, and medial gastrocnemius muscles than those with PM or ALS. The ratio of the remaining muscle area of the quadriceps relative to that of the hamstrings and the duration from onset to CT imaging were negatively correlated in patients with IBM, indicating that the anterior thigh muscles were preferentially affected over the posterior muscles. Characteristic muscular degeneration in the lower limbs on CT imaging may aid for making the diagnosis of IBM.


Assuntos
Esclerose Lateral Amiotrófica/diagnóstico por imagem , Miosite de Corpos de Inclusão/diagnóstico por imagem , Polimiosite/diagnóstico por imagem , Adulto , Esclerose Lateral Amiotrófica/patologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Debilidade Muscular , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Miosite de Corpos de Inclusão/patologia , Polimiosite/patologia , Tomografia Computadorizada por Raios X
10.
J Clin Neurosci ; 71: 135-140, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31501004

RESUMO

Cerebellar ataxia and Parkinson's disease are neurodegenerative disorders clinically characterized by motor disabilities including gait disturbance. This study aimed to investigate the usefulness of an infrared depth sensor device to quantitatively evaluate gait disturbances in patients with movement disorders. 25 ataxic, 25 Parkinson's disease, and 25 control subjects were enrolled and evaluated their walk. Stride length, feet interval, gait rhythm, and a ratio of the actual walking route length to the linear distance between the start and goal points (A/L ratio) were assessed and compared. Outcome correlations with clinical scales were also analyzed. The average stride length was shorter in ataxic subjects or Parkinson's disease subjects than in control subjects. The average feet interval was larger in ataxic subjects than in control subjects. The stride length coefficient of variation (CV), gait rhythm CV, and average and standard deviations of the A/L ratio were larger in ataxic or Parkinson's disease subjects than in control subjects. Ataxic subjects exhibited significant positive correlations between the CV of stride length or average feet interval and scale for the assessment and rating of ataxia scores or international cooperative ataxia rating scale scores. Parkinson's disease subjects exhibited a significant correlation between the average stride length, CV of stride length, or standard deviation of A/L ratio and unified Parkinson's disease rating scale score. The device used in this study differentiated the characteristics of gait disturbance in each movement disorder and quantitatively evaluated ataxia or Parkinson's disease severity, indicating its potential clinical utility across applications.


Assuntos
Ataxia Cerebelar/diagnóstico , Análise da Marcha/instrumentação , Doença de Parkinson/diagnóstico , Idoso , Feminino , Análise da Marcha/métodos , Humanos , Raios Infravermelhos , Pessoa de Meia-Idade
11.
Front Neurol ; 11: 757, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32849216

RESUMO

Inclusion body myopathy (IBM) with Paget's disease of bone (PDB) and frontotemporal dementia (IBMPFD) presents with multiple symptoms and an unknown etiology. Valosin-containing protein (VCP) has been identified as the main causative gene of IBMPFD. However, no studies on neurofilament light chain (NFL) as a cerebrospinal fluid (CSF) marker of axonal neurodegeneration or on YKL-40 as a CSF marker of glial neuroinflammation have been conducted in IBMPFD patients with VCP mutations. A 65-year-old man presented with progressive muscle atrophy and weakness of all limbs, non-fluent aphasia, and changes in personality and behavior. Cerebral MRI revealed bilateral frontal and temporal atrophy. 99mTc-HMDP bone scintigraphy and pelvic CT revealed remodeling changes and active osteoblastic accumulations in the right medial iliac bone. Muscle biopsy demonstrated multiple rimmed vacuoles in muscle cells with myogenic and neurogenic pathological alterations. After the patient was clinically diagnosed with IBMPFD, DNA analysis of the VCP gene revealed a cytosine (C) to thymine (T) (C→ T) mutation, resulting in an amino acid exchange of arginine to cysteine (p.R155C mutation). The CSF levels of NFL at two time points (12 years apart) were higher than those in non-dementia controls (CTR) and Alzheimer's disease (AD); lower than those in frontotemporal dementia with motor neuron disease (FTD-MND); and comparable to those in patients with behavioral variant frontotemporal dementia (bvFTD), progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS). The CSF levels of YKL-40 were comparable at both time points and higher than those in CTR; lower than those in FTD-MND; and comparable to those in bvFTD, PSP, CBS, and AD. The CSF levels of phosphorylated tau 181 (P-Tau) and total tau (T-Tau) were not significantly different from those in CTR and other neurodegenerative diseases, except those in AD, which were significantly elevated. This is the first report that demonstrates increased NFL and YKL-40 CSF levels in an IBMPFD patient with a VCP mutation (p.R155C); NFL and YKL-40 levels were comparable to those in bvFTD, PSP, CBS, and AD and higher than those in CTR. Our results suggest that IBMPFD neuropathology may involve both axonal neurodegeneration and glial neuroinflammation.

12.
Intern Med ; 59(9): 1219-1222, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32051380

RESUMO

We herein report the case of a 65-year-old woman diagnosed with myasthenia gravis (MG) after complaining of double vision. The patient had anti-low-density lipoprotein receptor-related protein 4 (LRP4) antibody in her serum, although antibodies against the acetylcholine receptor and muscle-specific tyrosine kinase were not detected. Chest computed tomography showed an anterior mediastinal tumor with a high uptake on fluorodeoxyglucose-positron emission tomography. Endoscopic thymectomy successfully ameliorated her ocular symptoms and showed the lesion to be thymoma. The present case revealed that anti-LRP4 antibody-associated MG can be associated with thymoma, which has been regarded as a rare complication of this disease thus far.


Assuntos
Miastenia Gravis/diagnóstico , Timoma/diagnóstico , Neoplasias do Timo/diagnóstico , Idoso , Autoanticorpos/sangue , Diagnóstico Diferencial , Feminino , Humanos , Proteínas Relacionadas a Receptor de LDL/imunologia , Miastenia Gravis/sangue , Miastenia Gravis/complicações , Tomografia por Emissão de Pósitrons , Timectomia , Timoma/complicações , Timoma/diagnóstico por imagem , Timoma/cirurgia , Neoplasias do Timo/complicações , Neoplasias do Timo/diagnóstico por imagem , Neoplasias do Timo/cirurgia , Tomografia Computadorizada por Raios X/efeitos adversos
13.
Rinsho Shinkeigaku ; 55(5): 333-8, 2015.
Artigo em Japonês | MEDLINE | ID: mdl-26028196

RESUMO

A 56-year-old man suffered from diffuse large B-cell lymphoma (DLBCL) originated from the stomach. He received R-CHOP therapy, and had a complete remission. However, at age 57, he experienced left shoulder pain and weakness of left arm, and his muscle weakness and sensory disturbance subacutely progressed to other limbs. Cervical and lumbosacral MRI showed enhanced extended lesions of cervical, thoracic, lumbar, and sacral nerve roots and cauda equina. Cerebrospinal fluid analysis revealed a sustained low glucose level. Nerve conduction study showed abnormalities of measurement parameters of F-waves in all limbs. A diagnosis of recurrent DLBCL presenting neurolymphomatosis could be established by repeated cytology of cerebrospinal fluid. He received high dose methotrexate therapy, but his symptoms were worsened to tetraplegia. It should be noticed that DLBCL can involve spinal nerve roots extensively.


Assuntos
Raízes Nervosas Espinhais/patologia , Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Líquido Cefalorraquidiano/citologia , Ciclofosfamida/administração & dosagem , Citodiagnóstico , Progressão da Doença , Doxorrubicina/administração & dosagem , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Imageamento por Ressonância Magnética , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Quadriplegia/etiologia , Indução de Remissão , Rituximab , Vincristina/administração & dosagem
14.
Intern Med ; 53(7): 793-5, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24694499

RESUMO

We herein report the case of a 67-year-old Japanese man diagnosed with sporadic Parkinson's disease (PD) at 52 years of age who presented with oculogyric crisis (OGC) in the off period. Ordinarily, OGC is caused by postencephalitic parkinsonism or the chronic use of antidopaminergic medications. The OGC began at 65 years of age and was associated with the wearing-off of symptoms. The dominant OGC feature was tonic deviations in eye posture induced by looking upward with prominent retrocollis. The administration of control dopaminergic medications led to improvements in the wearing-off phenomenon and OGC. This observation confirms that sporadic PD can induce OGC in the off period.


Assuntos
Transtornos da Motilidade Ocular/etiologia , Doença de Parkinson/diagnóstico , Transtornos da Percepção/etiologia , Idoso , Diagnóstico Diferencial , Humanos , Masculino , Transtornos da Motilidade Ocular/diagnóstico , Doença de Parkinson/complicações , Transtornos da Percepção/diagnóstico
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