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1.
J Stroke Cerebrovasc Dis ; 33(8): 107778, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38795797

RESUMEN

OBJECTIVES: Patients with acute ischemic stroke (AIS) often have an accumulation of pre-existing comorbidities, but its clinical impact on outcomes after mechanical thrombectomy (MT) remains unknown. Therefore, we examined whether comorbidity burden before AIS onset could predict clinical outcomes after MT. METHODS: In this retrospective cohort, we enrolled consecutive patients with community-onset AIS who underwent MT between April 2016 and December 2021. To evaluate each patient's comorbidity burden, we calculated Charlson comorbidity index (CCI), then classified the patients into the High CCI (≥ 3) and the Low CCI (< 3) groups. The primary outcome was a good neurological outcome at 90 days, defined as a modified Rankin scale 0-2 or no worse than the previous daily conditions. All-cause mortality at 90 days and hemorrhagic complications after MT were also compared between the two groups. We estimated the odds ratios and their confidence intervals using a multivariable logistic regression model. RESULTS: A total of 388 patients were enrolled, of whom 86 (22.2%) were classified into the High CCI group. Patients in the High CCI group were less likely to achieve a good neurological outcome (adjusted odds ratio of 0.26 [95% confidence interval, 0.12-0.58]). Moreover, symptomatic intracranial hemorrhage was more common in the High CCI (14.0% vs. 4.6%; adjusted odds ratio, 4.10 [95% confidence interval, 1.62-10.3]). CONCLUSIONS: Comorbidity burden assessed by CCI was associated with clinical outcomes after MT. CCI has the potential to become a simple and valuable tool for predicting neurological prognosis among patients with AIS and MT.


Asunto(s)
Comorbilidad , Accidente Cerebrovascular Isquémico , Trombectomía , Humanos , Masculino , Estudios Retrospectivos , Femenino , Anciano , Resultado del Tratamiento , Persona de Mediana Edad , Factores de Riesgo , Factores de Tiempo , Medición de Riesgo , Accidente Cerebrovascular Isquémico/epidemiología , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/terapia , Accidente Cerebrovascular Isquémico/mortalidad , Trombectomía/efectos adversos , Trombectomía/mortalidad , Anciano de 80 o más Años , Evaluación de la Discapacidad , Recuperación de la Función , Hemorragias Intracraneales/epidemiología , Hemorragias Intracraneales/mortalidad
2.
Am J Emerg Med ; 58: 120-125, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35679654

RESUMEN

OBJECTIVE: Central nervous system (CNS) infections are often suspected in adult patients with fever-associated seizures. However, it is unclear whether lumbar puncture (LP) is routinely required in patients with fever-associated seizures. This study aimed to examine the prevalence of meningitis and encephalitis in adult patients with fever-associated seizures and to evaluate whether LP is routinely required. METHODS: We retrospectively studied patients aged ≥16 years who presented to the emergency department with complaints of seizures and fever above 37.5 °C who were admitted to the hospital between January 2017 and December 2019. LP was performed when the emergency physician suspected meningitis or encephalitis. Neurologists assessed patients with normal cerebrospinal fluid (CSF) findings and those admitted without LP after hospitalization. A neurologist confirmed the diagnoses of meningitis and encephalitis. RESULTS: The study included 148 patients. Ninety-seven patients (65.5%) were male, and the median age was 60 years. LP was performed in 105 patients (70.9%), and 14 (13.4%) had CSF pleocytosis. Meningitis and encephalitis were diagnosed in nine patients (6.1%), of whom four (2.8%) had CNS infections. Patients diagnosed with meningitis and encephalitis were more likely to have Glasgow Coma Scale <13 (P = 0.03) and less likely to have a history of seizures or epilepsy (P = 0.04) and had higher C-reactive protein levels than the other patients (P = 0.02). CONCLUSION: The prevalence of meningitis or encephalitis is relatively low in adult patients with fever-associated seizures. Lumbar puncture is considered unnecessary to be performed routinely, but its indication should be carefully considered with reference to the clinical course, comorbidities, and blood tests. Further validation studies with larger sample sizes are needed to confirm the findings of this study.


Asunto(s)
Infecciones del Sistema Nervioso Central , Encefalitis , Meningitis , Convulsiones Febriles , Adulto , Femenino , Humanos , Masculino , Meningitis/diagnóstico , Persona de Mediana Edad , Estudios Retrospectivos , Convulsiones/diagnóstico , Convulsiones/epidemiología , Convulsiones/etiología , Punción Espinal
3.
Medicina (Kaunas) ; 58(6)2022 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-35744058

RESUMEN

Background and Objectives: Intrinsically disordered proteins (IDPs) and proteins containing intrinsically disordered regions (IDRs) are known to be involved in various human diseases. Since the IDPs/IDRs are fluctuating between many structural substrates, the dynamical behavior of the disease-related IDPs/IDRs needs to be characterized to elucidate the mechanisms of the pathogenesis of the diseases. As protein motions have a hierarchy ranging from local side-chain motions, through segmental motions of loops or disordered regions, to diffusive motions of entire molecules, segmental motions, as well as local motions, need to be characterized. Materials and Methods: Combined analysis of quasielastic neutron scattering (QENS) spectra with the structural data provides information on both the segmental motions and the local motions of the IDPs/IDRs. Here, this method is applied to re-analyze the QENS spectra of the troponin core domain (Tn-CD), various mutants of which cause the pathogenesis of familial cardiomyopathy (FCM), and α-synuclein (αSyn), amyloid fibril formation of which is closely related to the pathogenesis of Parkinson's disease, collected in the previous studies. The dynamical behavior of wild-type Tn-CD, FCM-related mutant Tn-CD, and αSyn in the different propensity states for fibril formation is characterized. Results: In the Tn-CD, the behavior of the segmental motions is shown to be different between the wild type and the mutant. This difference is likely to arise from changes in the intramolecular interactions, which are suggested to be related to the functional aberration of the mutant Tn-CD. In αSyn, concerted enhancement of the segmental motions and the local motions is observed with an increased propensity for fibril formation, suggesting the importance of these motions in fibril formation. Conclusions: Characterization of the segmental motions as well as the local motions is thus useful for discussing how the changes in dynamical behavior caused by the disease-related mutations and/or environmental changes could be related to the functional and/or behavioral aberrations of these proteins.


Asunto(s)
Proteínas Intrínsecamente Desordenadas , Enfermedad de Parkinson , Difusión , Humanos , Proteínas Intrínsecamente Desordenadas/química , Proteínas Intrínsecamente Desordenadas/metabolismo , Neutrones , Enfermedad de Parkinson/metabolismo
4.
FASEB J ; 33(3): 3647-3658, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30481062

RESUMEN

Pleiotropic protein promoting DNA repair A (PprA) is a key protein facilitating the extreme radiation resistance of Deinococcus radiodurans. PprA is a unique protein to the genus Deinococcus and exists as an oligomer ranging from a tetramer to an ∼100-mer depending on protein concentrations. Here, the X-ray crystal structure of PprA was determined to clarify how PprA confers radiation resistance. The tertiary structure of dimeric PprA was elucidated by using mutants obtained with random and site-directed mutagenesis methods (W183R and A139R); these mutants have disabled DNA binding and polymerization functions. Because the mutant A139R and W183R proteins have dimeric assemblies with 2 different interfaces (Interfaces 1 and 2), the linear and oligomerized PprA model was constructed as a left-handed face-to-face periodic screw structure. In addition, the linear structure in solution was confirmed by small-angle scattering experiments. The site-directed mutational analysis identified essential basic amino acids for DNA binding. These analytical data support the hypothesis that a complex assembly of PprA molecules, which are extended and have a screw structure, surrounds and stretches the DNA strand, acting as a novel guide to colocalize the DNA strands for efficient DNA repairs.-Adachi, M., Shimizu, R., Shibazaki, C., Satoh, K., Fujiwara, S., Arai, S., Narumi, I., Kuroki, R. Extended structure of pleiotropic DNA repair-promoting protein PprA from Deinococcus radiodurans.


Asunto(s)
Proteínas Bacterianas/genética , Reparación del ADN/genética , Deinococcus/genética , Aminoácidos/genética , ADN/genética , Tolerancia a Radiación/genética
5.
Neural Plast ; 2020: 7169025, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33224189

RESUMEN

[This corrects the article DOI: 10.1155/2017/9358092.].

6.
J Stroke Cerebrovasc Dis ; 29(6): 104798, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32249205

RESUMEN

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.


Asunto(s)
Hemorragia Cerebral/etiología , Hematoma/etiología , Linfoma de Células B/complicaciones , Neoplasias Vasculares/complicaciones , Anciano de 80 o más Años , Antígenos CD20/análisis , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Biomarcadores de Tumor/análisis , Biopsia , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/patología , Ciclofosfamida/administración & dosificación , Imagen de Difusión por Resonancia Magnética , Doxorrubicina/administración & dosificación , Hematoma/diagnóstico por imagen , Hematoma/patología , Humanos , Inmunohistoquímica , Linfoma de Células B/diagnóstico por imagen , Linfoma de Células B/tratamiento farmacológico , Linfoma de Células B/patología , Masculino , Prednisona/administración & dosificación , Rituximab/administración & dosificación , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Neoplasias Vasculares/diagnóstico por imagen , Neoplasias Vasculares/tratamiento farmacológico , Neoplasias Vasculares/patología , Vincristina/administración & dosificación
7.
J Struct Biol ; 205(2): 196-205, 2019 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-30599212

RESUMEN

Small-angle X-ray scattering experiments were carried out to investigate the structural changes of cardiac thin filaments induced by the cardiomyopathy-causing E244D mutation in troponin T (TnT). We examined native thin filaments (NTF) from a bovine heart, reconstituted thin filaments containing human cardiac wild-type Tn (WTF), and filaments containing the E244D mutant of Tn (DTF), in the absence and presence of Ca2+. Analysis by model calculation showed that upon Ca2+-activation, tropomyosin (Tm) and Tn in the WTF and NTF moved together in a direction to expose myosin-binding sites on actin. On the other hand, Tm and Tn of the DTF moved in the opposite directions to each other upon Ca2+-activation. These movements caused Tm to expose more myosin-binding sites on actin than the WTF, suggesting that the affinity of myosin for actin is higher for the DTF. Thus, the mutation-induced structural changes in thin filaments would increase the number of myosin molecules bound to actin compared with the WTF, resulting in the force enhancement observed for the E244D mutation.


Asunto(s)
Citoesqueleto de Actina/metabolismo , Cardiomiopatías/genética , Troponina T/genética , Troponina/metabolismo , Citoesqueleto de Actina/genética , Animales , Humanos , Mutación , Tropomiosina/genética , Tropomiosina/metabolismo , Troponina/genética
8.
Biochim Biophys Acta Proteins Proteom ; 1865(12): 1781-1789, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28923663

RESUMEN

Troponin (Tn), consisting of three subunits (TnC, TnI, and TnT), regulates cardiac muscle contraction in a Ca2+-dependent manner. Various point mutations of human cardiac Tn are known to cause familial hypertrophic cardiomyopathy due to aberration of the regulatory function. In this study, we investigated the effects of one of these mutations, K247R of TnT, on the picosecond dynamics of the Tn core domain (Tn-CD), consisting of TnC, TnI and TnT2 (183-288 residues of TnT), by carrying out the quasielastic neutron scattering measurements on the reconstituted Tn-CD containing either the wild-type TnT2 (wtTn-CD) or the mutant TnT2 (K247R-Tn-CD) in the absence and presence of Ca2+. It was found that Ca2+-binding to the wtTn-CD decreases the residence time of atomic motions in the Tn-CD with slight changes in amplitudes, suggesting that the regulatory function mainly requires modulation of frequency of atomic motions. On the other hand, the K247R-Tn-CD shows different dynamic behavior from that of the wtTn-CD both in the absence and presence of Ca2+. In particular, the K247R-Tn-CD exhibits a larger amplitude than the wtTn-CD in the presence of Ca2+, suggesting that the mutant can explore larger conformational space than the wild-type. This increased flexibility should be relevant to the functional aberration of this mutant.


Asunto(s)
Cardiomiopatías/genética , Neutrones , Mutación Puntual , Dispersión de Radiación , Troponina T/genética , Calcio/metabolismo , Cardiomiopatías/etiología , Humanos , Mutación , Conformación Proteica
9.
Neural Plast ; 2017: 9358092, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28326199

RESUMEN

We investigated the clinical predictors of the degree of recovery in patients with prolonged disorders of consciousness (PDC) caused by traumatic brain injury. Fourteen patients with PDC underwent two diffusion tensor imaging (DTI) studies; the first and second scans were performed at 345.6 ± 192.6 and 689.1 ± 272.2 days after the injury, respectively. In addition to the temporal changes in each of these diffusion parameters, fractional anisotropy (FA), mean diffusivity, axial diffusivity (AD), and radial diffusivity were assessed over a 1-year period. Relationship of clinical and DTI parameters with recovery from PDC (RPDC) was evaluated using Spearman's rank-correlation and stepwise multiple linear regression analysis. The mean FA and number of voxels with FA values > 0.4 (VsFA0.4) were significantly decreased at the second scan. A significant positive correlation was observed between the degree of RPDC and mean FA (r = 0.60) and VsFA0.4 (r = 0.68) as well as between the difference in VsFA0.4 (r = 0.63) and AD (r = 0.54) between the first and second scans. On multiple linear regression analysis, initial severity of PDC and the difference in AD remained significantly associated with the degree of RPDC. The microstructural white matter changes observed in this study indicate their potential relation with the degree of RPDC over the longer term.


Asunto(s)
Lesiones Traumáticas del Encéfalo/complicaciones , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Trastornos de la Conciencia/diagnóstico por imagen , Trastornos de la Conciencia/patología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Adulto , Anciano , Anciano de 80 o más Años , Anisotropía , Trastornos de la Conciencia/etiología , Imagen de Difusión Tensora , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Recuperación de la Función , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Adulto Joven
10.
Biochem Biophys Res Commun ; 459(3): 493-7, 2015 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-25747714

RESUMEN

Various biological functions related to cell motility are driven by the interaction between the partner proteins, actin and myosin. To obtain insights into how this interaction occurs, the internal dynamics of F-actin and myosin subfragment-1 (S1) were characterized by the quasielastic neutron scattering measurements on the solution samples of F-actin and S1. Contributions of the internal motions of the proteins to the scattering spectra were separated from those of the global macromolecular diffusion. Analysis of the spectra arising from the internal dynamics showed that the correlation times of the atomic motions were about two times shorter for F-actin than for S1, suggesting that F-actin fluctuates more rapidly than S1. It was also shown that the fraction of the immobile atoms is larger for S1 than for F-actin. These results suggest that F-actin actively facilitates the binding of myosin by utilizing the more frequent conformational fluctuations than those of S1.


Asunto(s)
Actinas/química , Actinas/metabolismo , Subfragmentos de Miosina/química , Subfragmentos de Miosina/metabolismo , Animales , Movimiento Celular/fisiología , Pollos , Elasticidad , Simulación de Dinámica Molecular , Difracción de Neutrones , Conformación Proteica , Dominios y Motivos de Interacción de Proteínas , Conejos
11.
No Shinkei Geka ; 43(4): 323-9, 2015 Apr.
Artículo en Japonés | MEDLINE | ID: mdl-25838303

RESUMEN

The flash visual evoked potential (VEP) is a useful diagnostic modality for visual preservation during surgery. Decreased VEP amplitude is recognized to indicate visual deterioration;however, whether intraoperative VEP can detect visual improvement remains unclear. We describe a craniopharyngioma case with a significant increase in VEP amplitude during surgery. A 67-year-old woman presented with progressive gait disturbance and impaired consciousness. Head magnetic resonance imaging demonstrated a sellar-suprasellar tumor compressing the optic chiasm upward with significant ventricular dilation. Her Glasgow Coma Scale was E3V3M5. Visual fields and acuity could not be examined because of impaired consciousness, and she could not see/recognize objects on a table. Preoperative VEP showed reproducible waveforms. Tumor removal by the extended transsphenoidal approach was performed with VEP monitoring. Increased VEP amplitude was observed after dural incision and persisted until the surgery ended. Postoperative VEP waveforms were also reproducible, but visual fields/acuity could not be examined because of cognitive dysfunction. Useful visual function was restored, and she became independent in daily life. The histological diagnosis was craniopharyngioma. The patient underwent ventriculo-peritoneal shunting for hydrocephalus 16 days after tumor removal. The postoperative course was uneventful and she was transferred to another hospital for rehabilitation. Intraoperative VEP may indicate visual improvement during surgery, which is a useful objective assessment for visual function in patients with impaired consciousness and cognitive dysfunction.


Asunto(s)
Craneofaringioma/cirugía , Potenciales Evocados Visuales , Anciano , Craneofaringioma/fisiopatología , Cardioversión Eléctrica , Femenino , Humanos , Imagen por Resonancia Magnética , Monitoreo Intraoperatorio , Neoplasias Hipofisarias , Resultado del Tratamiento
12.
J Stroke Cerebrovasc Dis ; 23(5): 805-10, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-23954610

RESUMEN

Spontaneous dissection of the vertebral artery (VA) is a major vascular lesion causing lateral medullary infarction (LMI). A dilated surface appearance of the VA is a feature of VA dissection and can be observed on basiparallel anatomic scanning (BPAS)-magnetic resonance imaging (MRI). The aim of this study was to validate BPAS-MRI in the diagnosis of VA dissection in patients with LMI. The subjects of the present study were 41 consecutive patients with LMI within 7 days of onset. The diagnosis of VA dissection was made with the clinical criteria-based diagnosis. Percent (%) dilatation of the VA on BPAS-MRI was calculated by comparing the maximum surface diameter of the intracranial VA to the diameter of the distal normal surface of the VA. Fourteen patients (34%) were diagnosed with VA dissection. The optimal cutoff % dilatation of the VA for dissection was more than 169%. The sensitivity and specificity of % dilatation of VA more than 169% and aneurysmal dilatation, stenosis, or occlusion on magnetic resonance angiography (MRA) for VA dissection were 92.9% and 81.5%, respectively. BPAS-MRI combined with time-of-flight-MRA is a useful tool for the diagnosis of VA dissection in patients with acute LMI.


Asunto(s)
Infarto Cerebral/diagnóstico , Angiografía por Resonancia Magnética , Disección de la Arteria Vertebral/diagnóstico , Arteria Vertebral/patología , Adulto , Anciano , Infarto Cerebral/patología , Dilatación Patológica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Sistema de Registros , Reproducibilidad de los Resultados , Disección de la Arteria Vertebral/patología
13.
Cureus ; 16(6): e63417, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39077292

RESUMEN

The diagnosis of intravascular large B-cell lymphoma (IVLBCL) is often challenging owing to its nonspecific clinical manifestations and imaging findings. Herein, we present a rare case of IVLBCL in which seizure was the initial symptom, and unilateral hemispheric hyperperfusion on arterial spin labeling (ASL) was the only abnormal finding observed on brain magnetic resonance imaging (MRI). A 68-year-old male with a history of hypertension and type 2 diabetes was transferred to the emergency room owing to the sudden onset of altered consciousness and abnormal behavior. Upon arrival, the patient was disoriented and confused, and cerebrospinal fluid analysis revealed pleocytosis and elevated protein level. Even after the administration of acyclovir and antiepileptic drugs, his consciousness remained impaired, with repeated transient right hemiparesis indicating a focal seizure. The initial and follow-up MRI scans showed no obvious abnormalities in diffusion-weighted imaging (DWI), T2-weighted imaging, or susceptibility-weighted imaging (SWI); however, ASL revealed markedly increased blood flow to the left hemisphere. Subsequently, the rapid elevation of serum lactate dehydrogenase (LDH) and soluble interleukin-2 receptor (sIL-2R) levels after admission led to the diagnosis of IVLBCL by random skin biopsy and bone marrow examination. Despite the initiation of chemotherapy, the patient developed tumor lysis syndrome and succumbed to multiple organ failure. This case underscores the importance of considering IVLBCL in adult patients with refractory seizures and highlights the potential utility of ASL on MRI for early diagnosis.

14.
Int J Infect Dis ; 147: 107201, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39103011

RESUMEN

Burkholderia cepacia complex (BCC) encompasses opportunistic pathogen with various clinical manifestations ranging from no symptoms to severe respiratory infections and septicemia. Central nervous system infections caused by BCC are rare. To the best of our knowledge, we present the first reported case of choroid plexitis caused by BCC after severe COVID-19. A 67-year-old woman who had been previously diagnosed with COVID-19 presented with a mild fever and headache. Gadolinium-enhanced T1-weighted brain magnetic resonance imaging showed contrast effects in the right choroid plexus and encapsulated abscess. Gram staining of cerebrospinal fluid revealed the presence of gram-negative rods. Broad-range polymerase chain reaction amplification of 16S ribosomal RNA from the cerebrospinal fluid, followed by sequence analysis, identified BCC; thus, choroid plexitis caused by BCC was diagnosed. After prolonged antimicrobial treatment with a multiantibiotic regimen, the patient recovered completely. This case highlights the importance of long-term therapy with a carefully selected multiantibiotic regimen to achieve complete recovery after BCC infection.


Asunto(s)
Infecciones por Burkholderia , Complejo Burkholderia cepacia , COVID-19 , SARS-CoV-2 , Humanos , Femenino , COVID-19/complicaciones , COVID-19/diagnóstico , Anciano , Complejo Burkholderia cepacia/aislamiento & purificación , Infecciones por Burkholderia/diagnóstico , Infecciones por Burkholderia/tratamiento farmacológico , Antibacterianos/uso terapéutico , Plexo Coroideo/microbiología , Plexo Coroideo/patología , Plexo Coroideo/diagnóstico por imagen , Imagen por Resonancia Magnética , Coroiditis/microbiología , Coroiditis/tratamiento farmacológico , Coroiditis/diagnóstico
15.
Cureus ; 16(7): e63972, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39104995

RESUMEN

Meningoencephalitis caused by varicella-zoster virus (VZV) is a serious condition requiring prompt antiviral treatments, but magnetic resonance imaging (MRI) findings are often normal, limiting early diagnostic utility. We report a case of severe VZV-associated meningoencephalitis characterized by diffuse T2 hyperintense lesions covering the brain surface on MRI, presumed to be vasogenic edema. An immunocompetent 78-year-old Japanese woman presented with a disturbance of consciousness preceded by seven days of headache. On admission, she was in a semi-coma with intermittent convulsive seizures and had a localized skin rash with blisters on her back. Brain MRI showed diffuse T2 hyperintensity on the brain surface with an elevated apparent diffusion coefficient and the marked gadolinium-contrast enhancement of the pia-arachnoid membrane and vessel walls. Polymerase chain reaction using cerebrospinal fluid revealed the presence of VZV, and then she was diagnosed with VZV-associated meningoencephalitis. Treatment with acyclovir and corticosteroids was initiated, leading to some clinical improvement; however, the patient developed acute non-occlusive mesenteric ischemia and died on the 10th day of hospitalization. The characteristic MRI findings observed in our patient may be useful in considering the pathogenesis and early diagnosis of this rare entity.

16.
Thorac Cancer ; 15(23): 1772-1775, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38924375

RESUMEN

We present the case of a 34-year-old Japanese man with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer and brain metastases. After central nervous system (CNS) disease progression with alecintib and brigatinib, treatment with lorlatinib resulted in a good intracranial response. In this case, we investigated brain penetration ratio of brigatinib using cerebrospinal fluid and paired serum samples, and the ratio was 0.012. Further, we investigated resistance mechanisms via next-generation sequencing (NGS) using lung biopsy at lung cancer diagnosis and brain biopsy sample at progressive disease of brigatinib. No apparent resistance mechanism of known ALK resistance, such as ALK mutations, amplifications, epithelial-mesenchymal transition (EMT) and bypass pathway activation were detected. Taken together, we speculate that the low CNS penetration rate of brigatinib confers CNS progression. Further studies are warranted to reveal the resistance mechanism and propose a treatment strategy for CNS progression in ALK-positive patients.


Asunto(s)
Adenocarcinoma del Pulmón , Aminopiridinas , Quinasa de Linfoma Anaplásico , Carbazoles , Resistencia a Antineoplásicos , Lactamas Macrocíclicas , Lactamas , Neoplasias Pulmonares , Compuestos Organofosforados , Piperidinas , Pirazoles , Pirimidinas , Humanos , Masculino , Compuestos Organofosforados/uso terapéutico , Compuestos Organofosforados/farmacología , Compuestos Organofosforados/administración & dosificación , Lactamas/uso terapéutico , Adulto , Aminopiridinas/uso terapéutico , Aminopiridinas/farmacología , Quinasa de Linfoma Anaplásico/genética , Pirimidinas/uso terapéutico , Pirimidinas/farmacología , Pirimidinas/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Lactamas Macrocíclicas/uso terapéutico , Lactamas Macrocíclicas/farmacología , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/genética , Pirazoles/uso terapéutico , Pirazoles/farmacología , Carbazoles/uso terapéutico , Carbazoles/farmacología , Carbazoles/administración & dosificación , Piperidinas/uso terapéutico , Piperidinas/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/secundario
17.
Thorac Cancer ; 2024 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-39425544

RESUMEN

INTRODUCTION: Paraneoplastic neurological syndrome (PNS) is associated with small-cell lung cancer (SCLC). However, the frequency and characteristics of PNS and the efficacy of anticancer treatment for these patients have not been investigated in the Japanese/Asian population previously. Therefore, we aimed to better understand PNS by evaluating real-world data from patients with PNS complicated by SCLC. METHODS: Patients diagnosed with Stage II-IV SCLC at a single center between August 2007 and April 2021 were retrospectively analyzed. The primary outcome was the incidence of PNS. The secondary outcomes were the change in performance status (PS) after treatment commencement and outcomes following anticancer treatment, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS: A total of 318 patients were evaluated; PNS was present in 2.8% (n = 9) of the overall population. All patients with PNS exhibited poor Eastern Cooperative Oncology Group PS (≥2); moreover, 78% of patients had a PS score of 3-4. An improvement in PS was observed in 56% (n = 5) of patients. Patients with PNS exhibited treatment efficacies similar to patients without PNS (ORR: 89% vs. 83%, p = 1.0; PFS: 7.6 vs. 5.7 months, p = 0.69; OS: not reached vs. 15.6 months, p = 0.23). CONCLUSIONS: A total of 2.8% of patients had SCLC complicated by PNS, with poor PS observed. However, anticancer therapy led to an improvement in PS and comparable ORR, as well as PFS and OS similar to those observed in patients without PNS. Thus, anticancer therapy should be considered in patients with PNS.

18.
Artículo en Inglés | MEDLINE | ID: mdl-39322544

RESUMEN

Endovascular treatment (EVT) is a potential therapeutic option for extracranial vertebral artery (VA) stenosis; however, its efficacy or optimal procedures remain unknown. This study aimed to investigate the recent status of EVT for extracranial VA stenosis in Japan using a nationwide registry. We conducted a post hoc analysis of the Japanese Registry of Neuroendovascular Therapy 4 that enrolled patients who underwent EVT at 166 hospitals in Japan from 2015 to 2019. The outcomes of this study were as follows: procedural success indicating that the planned procedure was completed, modified Rankin Scale (mRS) score at 30 days, and procedure-related complications evaluated according to the procedure during EVT (percutaneous transluminal angioplasty vs. stenting and with or without the use of embolic protection devices [EPDs]). Of 308 eligible patients, 301 (95%) were treated for atherosclerotic stenosis, predominantly by stenting (74%). EPDs were used in 43%, primarily with the distal balloon (63%). The proportion of procedural success was 98%. Functional independence (mRS of 0-2) at 30 days was achieved in 80% of the total cohort, and there were no differences between patients treated with or without stenting or EPDs (74% vs. 82%, p = 0.12, and 80% vs. 80%, p = 0.93). Procedural complications occurred in 28 (9.1%) patients similarly in each group, with distal embolism and vessel dissection being common. In conclusion, EVT is a reasonable option for extracranial VA stenosis as a daily clinical practice. This study emphasizes the potential of EVT in managing extracranial VA stenosis and the need for further research to refine treatment strategies.

19.
J Neurol Sci ; 466: 123247, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39326368

RESUMEN

BACKGROUND: Endovascular therapy (EVT) has shown high therapeutic efficacy for acute large vessel occlusion (LVO); however, recanalization is unsuccessful in some cases. This study aimed to examine the characteristics and prognostic impact of unsuccessful recanalization after EVT compared with medical treatment alone. METHODS: We conducted a post hoc analysis of RESCUE-Japan Registry 2, a nationwide registry of 2408 consecutive patients with acute LVO. Patients without successful recanalization after EVT (thrombolysis in cerebral infarction grade ≤ 2a) were classified into the Unsuccessful EVT group, and compared with the No-EVT group. To account for selection bias, the outcomes were compared in a propensity score-matched cohort. The outcomes included the modified Rankin Scale (mRS) score at 90 days and intracranial hemorrhage within 72 h after the LVO onset. RESULTS: Among 188 (14.7 %) patients in the Unsuccessful EVT group out of 1281 who underwent EVT, 147 were matched with the No-EVT group, with comparable baseline characteristics. Patients in the Unsuccessful EVT group had a higher distribution of mRS score at 90 days and were less likely to achieve mRS 0-2 compared to those in the No-EVT group (23 % vs. 34 %, OR:0.58, 95 % CI:0.35-0.98). All-cause mortality was higher in the Unsuccessful EVT group (16 % vs. 6.8 %, OR: 2.54, 95 % CIs: 1.16-5.55). Symptomatic intracranial hemorrhage was more frequently observed in the Unsuccessful EVT group (5.4 % vs. 0.7 %, OR: 8.40, 95 % CIs: 1.04-68.1). CONCLUSIONS: The clinical outcomes of patients without successful recanalization after EVT were worse than those who did not undergo EVT.

20.
Neurol Med Chir (Tokyo) ; 64(8): 309-315, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38839294

RESUMEN

We reported the main results of the Japanese Registry of Neuroendovascular Therapy (JR-NET) 4, a nationwide surveillance of therapy (NET) in Japan from January 2015 to December 2019. JR-NET 4 registered consecutive patients who underwent NETs by Japan Society of Neuroendovascular Therapy (JSNET) -certified specialists. The primary endpoint was functional independence (mRS score of 0-2) at 30 days post-NET, with secondary endpoints focusing on technical success and major adverse events within 30 days.A total of 63,230 patients and 60,354 NET procedures from 166 participating centers were analyzed. During the study period, NET cases have consistently increased, with an increase in the proportion of elderly patients. A significant trend shift was observed in the distribution of NET procedures, with endovascular treatment for acute ischemic stroke that showed a dramatic increase in 5 years. This trend aligns with key randomized clinical trials from 2015 that presented the efficacy of this treatment. Clinical outcomes at 30 days posttreatment revealed that endovascular treatment for acute ischemic stroke and other NETs maintained safety and effectiveness despite varying prevalence of functional independence between target diseases. The study also observed a steady increase in emergency treatment cases, reflecting the increase in acute ischemic stroke, a time-sensitive medical condition.This comprehensive surveillance highlights the trend of NET practices in Japan, driven by clinical evidence and advancements in treatment devices. Although these findings were specific to Japan, they offer valuable insights into the broader trends in NETs and acute stroke care.


Asunto(s)
Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Sistema de Registros , Humanos , Japón , Procedimientos Endovasculares/tendencias , Anciano , Masculino , Femenino , Persona de Mediana Edad , Accidente Cerebrovascular Isquémico/terapia , Accidente Cerebrovascular Isquémico/epidemiología , Anciano de 80 o más Años , Resultado del Tratamiento , Pueblos del Este de Asia
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