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BACKGROUND AND PURPOSE: Takotsubo cardiomyopathy (TCM) is a serious autonomic complication of Guillain-Barré syndrome (GBS). However, the association between TCM and GBS has not been investigated in detail. We investigated the characteristics of GBS patients with TCM (GBS-TCM). METHODS: Clinical features and anti-ganglioside antibody between the GBS-TCM patients and 62 classical GBS patients without TCM as control patients were compared. RESULTS: Eight GBS-TCM patients were identified, in whom TCM was diagnosed at a mean of 6.5 [range 3-42] days after the onset of GBS. The age at onset of GBS was elder in the GBS-TCM patients than in the control GBS patients (76.5 [56-87] vs. 52 [20-88] years, p < 0.01). Notably, cranial nerve deficits, particularly in the lower cranial nerves, were observed in all GBS-TCM patients (100% vs. 41.9%, p < 0.01). Additionally, the GBS-TCM patients showed a higher GBS disability score at nadir (5 [4-5] vs. 4 [1-5], p < 0.01), and lower Medical Research Council sum scores at admission and nadir (37 [30-44] vs. 48 [12-60] at admission, p < 0.05, and 20 [12-44] vs. 40 [0-60] at nadir, p < 0.05, respectively). Mechanical ventilation was more frequently required in the GBS-TCM patients (62.5% vs. 11.3%, p < 0.01). Three GBS-TCM patients were positive for anti-ganglioside antibodies. CONCLUSIONS: TCM occurred at a relatively early phase of GBS. The characteristics of GBS-TCM were the elder, lower cranial nerve involvements, severe limb weakness, and respiratory failure.
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Síndrome de Guillain-Barré , Cardiomiopatía de Takotsubo , Humanos , Cardiomiopatía de Takotsubo/etiología , Cardiomiopatía de Takotsubo/complicaciones , Síndrome de Guillain-Barré/complicaciones , Síndrome de Guillain-Barré/fisiopatología , Femenino , Persona de Mediana Edad , Anciano , Masculino , Anciano de 80 o más Años , Adulto , Adulto Joven , Gangliósidos/inmunología , Autoanticuerpos/sangre , Estudios RetrospectivosRESUMEN
Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic neurodegenerative disease. This multicenter, randomized phase 3 study evaluated the efficacy and safety of 0.3 mg/kg intravenous mogamulizumab, a monoclonal antibody targeting-CC chemokine receptor 4, every 12 weeks in HAM/TSP patients. This study comprised a 24-week double-blind, placebo-controlled period, 24-week open-label period, and extension treatment period. The primary endpoint was the proportion of patients with a ≥ 1-grade improvement in the Osame motor disability score (OMDS). Secondary endpoints were changes in HTLV-1 proviral load, 10-m timed walk, cerebrospinal fluid (CSF) neopterin levels, and safety. The exploratory endpoint was CSF chemokine C-X-C motif ligand 10 (CXCL10) levels. Thirty-four and 33 patients were randomized to mogamulizumab and placebo arms, respectively. At the end of the double-blind period, no significant difference was found in the OMDS improvement rate or other secondary efficacy endpoints assessing motor activities. However, the mogamulizumab arm showed a significant decrease in HTLV-1 proviral load (- 59.39 ± 29.91% vs. placebo 2.32 ± 36.31%) and CSF neopterin (p < 0.001)/CXCL10 levels (p = 0.004). The baseline OMDS pattern and the 60-80% HTLV-1 proviral load reduction were sustained through the open-label and extension treatment periods. Although a higher incidence of rash (69.2%) was reported, the safety profile was similar compared with a previous phase 1/2a study. We found no significant difference in clinical benefit; however, mogamulizumab may provide long-term clinical benefit by preventing disease progression, as CSF neopterin/CXCL10 levels are associated with long-term prognosis in HAM/TSP.Clinical Trial Registration Number: NCT03191526 (registered date: 6-June-2017).
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Anticuerpos Monoclonales Humanizados , Virus Linfotrópico T Tipo 1 Humano , Neopterin , Paraparesia Espástica Tropical , Humanos , Método Doble Ciego , Anticuerpos Monoclonales Humanizados/administración & dosificación , Masculino , Persona de Mediana Edad , Femenino , Paraparesia Espástica Tropical/tratamiento farmacológico , Paraparesia Espástica Tropical/líquido cefalorraquídeo , Adulto , Anciano , Neopterin/líquido cefalorraquídeo , Virus Linfotrópico T Tipo 1 Humano/efectos de los fármacos , Quimiocina CXCL10/líquido cefalorraquídeo , Carga Viral/efectos de los fármacos , Resultado del TratamientoRESUMEN
Background and objective: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral microvascular disease characterized by the development of vascular dementia and lacunar infarctions. This study aimed to identify the genetic and clinical features of CADASIL in Japan. Methods: We conducted genetic analysis on a case series of patients clinically diagnosed with CADASIL. Clinical and imaging analyses were performed on 32 patients with pathogenic mutations in the NOTCH3 gene. To assess the presence of cerebral microbleeds (CMBs), we utilized several established rating scales including the Fazekas scale, Scheltens rating scale, and Microbleed Anatomical Rating Scale, based on brain MRI images. Results: Among the 32 CADASIL patients, 24 cases were found carrying the R75P mutation in NOTCH3, whereas the remaining eight cases had other NOTCH3 mutations (R75Q, R110C, C134F, C144F, R169C, and R607C). The haplotype analysis of the R75P mutation uncovered the presence of a founder effect. A brain MRI analysis revealed that cases with the R75P mutation had a significantly higher total number of CMBs, particularly in the thalamus when compared to patients with other NOTCH3 mutations. Among 15 out of 24 cases with the R75P mutation, we observed a notable clustering of CMBs in the thalamus, termed microbleed clustering in thalamus sign (MCT sign). Conclusion: We propose that the MCT sign observed in NOTCH3 R75P-related CADASIL patients may serve as a potentially characteristic imaging feature. This finding offers further insights into the interactions between genotypes and phenotypes between NOTCH3 and CADASIL.
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BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder that causes motor symptoms and autonomic dysfunction. However, autonomic function tests commonly performed in PD can only evaluate either the sympathetic or parasympathetic nervous system. Therefore, the purpose of this pilot study is to investigate whether power spectral analysis of heart rate variability could detect both sympathetic and parasympathetic nervous dysfunctions in patients with PD. METHODS: Seventeen patients with PD and 11 healthy control subjects underwent electrocardiogram recording for the spectral analysis of heart rate variability to obtain values of low-frequency (LF) (0.04-0.15 Hz) and high-frequency (HF) (0.15-0.4 Hz) powers. Moreover, we examined the coefficient of variation of R-R intervals (CVRR) as a parameter of parasympathetic function in all participants and performed 123I-metaiodobenzylguanidine scintigraphy to measure the heart-to-mediastinum ratio as a parameter of cardiac sympathetic innervation in patients with PD. RESULTS: The median age of control subjects and PD patients was 63 and 66 years old, respectively. The median Hoehn and Yahr scale of PD patients was stage 2. The values of resting LF and HF powers widely varied. The median values of resting LF powers of control subjects and PD patients and those of HF powers were 169 and 70 ms2, 279 and 65 ms2, respectively, the difference was statistically insignificant. Approximately 41% of patients with PD had values below the first quartile of resting LF powers (< 58 ms2) or HF powers (< 50 ms2); however, no control subject had such low values. Positive correlations were found between resting LF powers and heart-to-mediastinum ratios of 123I-metaiodobenzylguanidine uptake (r = 0.6) and between resting HF powers and CVRRs (r = 0.7). The resting LF power was also associated with CVRRs and constipation. Furthermore, a positive correlation was observed between resting LF powers and resting HF powers in patients with PD (r = 0.8). CONCLUSIONS: The power spectral analysis of heart rate variability may be useful as a screening tool for detecting autonomic dysfunctions by detecting low resting LF and HF powers in patients with PD. Sympathetic and parasympathetic nerves may be concurrently damaged in patients with PD.
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Enfermedad de Parkinson , Disautonomías Primarias , Anciano , Frecuencia Cardíaca/fisiología , Humanos , Persona de Mediana Edad , Sistema Nervioso Parasimpático , Enfermedad de Parkinson/complicaciones , Proyectos PilotoRESUMEN
BACKGROUND: Recessive mutations in SLC12A6 have been linked to hereditary motor sensory neuropathy with agenesis of the corpus callosum. Patients with early-onset peripheral neuropathy associated with SLC12A6 heterozygous variants were reported in 2016. Only five families and three variants have been reported to date, and the spectrum is unclear. Here, we aim to describe the clinical and mutation spectra of SLC12A6-related Charcot-Marie-Tooth (CMT) disease in Japanese patients. METHODS: We extracted SLC12A6 variants from our DNA microarray and targeted resequencing data obtained from 2598 patients with clinically suspected CMT who were referred to our genetic laboratory by neurological or neuropediatric departments across Japan. And we summarized the clinical and genetic features of these patients. RESULTS: In seven unrelated families, we identified one previously reported and three novel likely pathogenic SLC12A6 heterozygous variants, as well as two variants of uncertain significance. The mean age of onset for these patients was 17.5 ± 16.1 years. Regarding electrophysiology, the median motor nerve conduction velocity was 39.6 ± 9.5 m/sec. For the first time, we observed intellectual disability in three patients. One patient developed epilepsy, and her brain MRI revealed frontal and temporal lobe atrophy without changes in white matter and corpus callosum. CONCLUSIONS: Screening for the SLC12A6 gene should be considered in patients with CMT, particularly those with central nervous system lesions, such as cognitive impairment and epilepsy, regardless of the CMT subtype.
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Enfermedad de Charcot-Marie-Tooth , Simportadores , Adolescente , Adulto , Enfermedad de Charcot-Marie-Tooth/genética , Niño , Preescolar , Femenino , Heterocigoto , Humanos , Lactante , Japón , Mutación , Simportadores/genética , Adulto JovenRESUMEN
Here, we present the case of a 15-year-old Japanese girl with Dystonia 28, childhood-onset; DYT28 (MIM#606834) showing early-onset generalized progressive dystonia and status dystonicus. The patient was genetically undiagnosed and had not responded to various medications. By trio-based whole exome sequencing and in silico analyses, we identified a de novo heterozygous variant of KMT2B: NM_014727.2: c.7828C > T, p(Arg2610Cys). Globus pallidus internus deep brain stimulation (GPi-DBS) therapy was considered; however, the therapy could not be performed due to the patient's poor nutritional status and repeated infections. GPi-DBS is considered to be an effective treatment for patients with KMT2B mutations, and genetic diagnosis is important before progression to status dystonicus.
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Distonía/genética , N-Metiltransferasa de Histona-Lisina/genética , Niño , Distonía/patología , Femenino , Humanos , Mutación Missense , FenotipoRESUMEN
Spinocerebellar ataxia type 8 (SCA8) is a rare hereditary cerebellar ataxia showing mainly pure cerebellar ataxia. We herein report cases of SCA8 in Japanese monozygotic twins that presented with nystagmus, dysarthria, and limb and truncal ataxia. Their ATXN8OS CTA/CTG repeats were 25/97. They showed similar manifestations, clinical courses, and cerebellar atrophy on magnetic resonance imaging. Some of their pedigrees had nystagmus but not ataxia. These are the first monozygotic twins with SCA8 to be reported anywhere in the world. Although not all subjects with the ATXN8OS CTG expansion develop cerebellar ataxia, these cases suggest the pathogenesis of ATXN8OS repeat expansions in hereditary cerebellar ataxia.
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ARN Largo no Codificante/genética , Degeneraciones Espinocerebelosas/genética , Degeneraciones Espinocerebelosas/patología , Gemelos Monocigóticos , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética , Linaje , Expansión de Repetición de TrinucleótidoRESUMEN
Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) is a motor and sensory neuronopathy with autosomal dominant inheritance, adult onset, slowly progressive course, and is associated with TRK-fused gene (TFG) mutation. At advanced stages, respiratory failure and dysphagia becomes life-threatoning, and patients typically die by their 70s. Although there is currently no evidence for effective treatment, a therapy may be found by elucidation of the function of TFG. Recently its pathomechanism has been proposed to be associated with abnormalities in protein transfer from the endoplasmic reticulum. Such pathomechanisms might involve a similar process in amyotrophic lateral sclerosis; thus, its pathomechanisms and treatment strategy might make it a good model for neurodegenerative disorders. It is of great value to clarify the natural history of HMSN-P, in oder to judge the treatment effect. By evaluating 97 patients (79 out of 97 were examined and all confirmed with p.Pro 285 Leu mutation) in this study, it was confirmed that this disease follows a uniform course in the earlier stages, and there are individual differences in the onset between 20 and 30 years. Such uniformity might be due to the proposed single gene abnormality. At advanced stages, there are larger individual differences in the progression, but the reasons for these are unknown. Longer survival might be achieved with a better care for respiratory failure and dysphagia if such cares were undertaken at appropriate times.
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BACKGROUND: Cortical gray matter (GM) and white matter (WM) deterioration are signals of neurodegeneration and increased dementia risk; however, their specific etiologies in dementia-free aging is unclear. OBJECTIVE: The objective of this study was to examine potentially modifiable risk factors of GM and WM degeneration in a well-characterized cohort of dementia-free elderly. METHODS: 96 Okinawan elderly participants (age 83.6) from the Keys to Optimal Cognitive Aging Project (KOCOA) underwent MRI and cognitive evaluation. Serum markers of inflammation (interleukin-6 (IL-6), high sensitivity C-reactive protein), cerebrovascular disease (systolic blood pressure (SBP) 140+, hemoglobin A1C (HgbA1C), total cholesterol), and essential minerals (copper (Cu), magnesium, and calcium) were examined in relation to mean cortical thickness (MCT) and white matter hyperintensities (WMH), adjusting for age and gender. Voxel-based morphometry (VBM) analyses identified relationships between regional GM density and the above markers. RESULTS: Decreased MCT was associated with SBP 140 + (pâ=â0.029) and increased serum IL-6 (pâ=â0.036), HgbA1C (pâ=â0.002), and Cu (pâ=â0.025). In VBM analyses, increased IL-6, HgbA1C, and Cu were associated with decreased GM density in temporal lobe regions. HgbA1C (pâ=â0.004) was associated with greater WMH volume. CONCLUSIONS: Peripheral markers of Cu, CVD risk, and inflammation are associated with MRI-markers of decreased brain health in dementia-free Okinawan elderly, with regional cortical thinning in areas involved in early accumulation of Alzheimer's disease pathology. Results identify potentially modifiable biomarkers as targets in the prevention of dementia in older individuals.
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Envejecimiento , Corteza Cerebral/patología , Demencia/complicaciones , Demencia/patología , Anciano , Anciano de 80 o más Años , Corteza Cerebral/diagnóstico por imagen , Cobre/sangre , Demencia/diagnóstico por imagen , Demencia/epidemiología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Interleucina-6/sangre , Japón/epidemiología , Imagen por Resonancia Magnética , Masculino , Pruebas Neuropsicológicas , Análisis de Regresión , Estudios Retrospectivos , Factores de Riesgo , Sustancia Blanca/patologíaRESUMEN
OBJECTIVES: In this study, we evaluated the prevalence of lower urinary tract symptoms and the associated clinical features in patients with chronic stroke. METHODS: Patients with stroke who had been regularly followed up at general medical hospitals in Okinawa, Japan were enrolled in the study. The patients were asked to complete a self-reported questionnaire regarding their physical activity, medical history, and the core lower urinary tract symptom score (CLSS) questionnaire, with anonymity. The association between each urinary disturbance category and the clinical characteristics of the patients such as age, gender, physical activity, and underlying disease was evaluated. RESULTS: In total, 51 patients (33 men and 18 women; mean age, 71.7 years) were eligible for analysis. The average time after the first stroke onset was 8.5 years. Nocturia and urgency incontinence had the greatest impact on the quality of life. Overactive bladder symptoms such as nocturia, urgency, urgency incontinence, and stress urinary incontinence were associated with age, female sex, and having a co-existing medical condition (such as ischemic heart disease, hypertension, and depression). Voiding symptoms such as slow stream and straining were associated with age and physical activity after stroke. CONCLUSIONS: Storage symptom is associated with not only neurological deficits but also sex and the presence of general diseases, whereas voiding symptom is influenced by physical activity in patients with chronic stroke. Therefore, lower urinary tract symptoms should be carefully monitored and physical rehabilitation should also be considered in patients with stroke.
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Ejercicio Físico , Síntomas del Sistema Urinario Inferior/epidemiología , Accidente Cerebrovascular/epidemiología , Factores de Edad , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Comorbilidad , Trastorno Depresivo/epidemiología , Femenino , Humanos , Hipertensión/epidemiología , Japón/epidemiología , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/epidemiología , Nocturia/epidemiología , Prevalencia , Calidad de Vida , Factores Sexuales , Encuestas y Cuestionarios , Vejiga Urinaria Hiperactiva/epidemiología , Incontinencia Urinaria/epidemiología , Incontinencia Urinaria de Esfuerzo/epidemiología , Incontinencia Urinaria de Urgencia/epidemiologíaRESUMEN
OBJECTIVE: It is not known whether autonomic neuropathy is a feature of Sjögren's syndrome (SS) or whether it is related to circulating antiganglionic acetylcholine receptor (gAChR) antibodies. The goal of the present study was to investigate the autonomic dysfunction in patients with SS and the associations between autonomic dysfunction, anti-gAChR antibodies, and clinical features of SS. METHODS: (1) The first observational study tested for the presence of gAChR antibodies in the serum samples from 39 patients with SS (absent information regarding autonomic symptoms) and healthy volunteers. (2) In the second study, serological and clinical data from 10 Japanese patients diagnosed with SS were reviewed. These patients showed autonomic dysfunction, and luciferase immunoprecipitation systems (LIPS) test was conducted to detect anti-α3 and anti-ß4 gAChR antibodies. (3) In the final analysis, we combined the data of seropositive SS patients with autonomic symptom from the first study with all of the patients from the second study, and analyzed the clinical features. RESULTS: (1) The LIPS assay revealed that anti-gAChRα3 and anti-gAChRß4 antibodies were detected in the sera from patients with SS (23.1%, 9/39). Five of nine SS patients had autonomic symptoms. (2) Anti-α3 and anti-ß4 gAChR antibodies were also detected in 80.0% (8/10) of patients with SS with autonomic symptoms. Six of the ten patients were diagnosed as having SS after neurological symptoms developed. These seropositive patients had predominant and severe autonomic symptoms and were diagnosed with autonomic neuropathy. (3) Thirteen of fifteen SS patients with autonomic symptoms (86.7%) were seropositive for anti-gAChR antibodies, and we confirmed sicca complex, orthostatic hypotension, upper and lower gastrointestinal (GI) symptoms, and bladder dysfunction at high rates. CONCLUSION: The present results suggest the possibility of anti-gAChR antibodies aiding the diagnostics of SS with autonomic dysfunction.
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Autoanticuerpos/sangre , Receptores Colinérgicos/inmunología , Síndrome de Sjögren/inmunología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Síndrome de Sjögren/sangreRESUMEN
BACKGROUND: Epidemiological studies have found frequent consumption of fatty fish is protective against cognitive decline. However, the association between circulating omega-3 polyunsaturated fatty acid (PUFA) levels and cognitive functions among the oldest old is not well known. OBJECTIVE: To examine the association between serum PUFA levels and cognitive function among community-dwelling, non-demented elderly aged over 80 years old. METHODS: The data came from the Keys to Optimal Cognitive Aging (KOCOA) study; an ongoing cohort of relatively healthy volunteers aged over 80 years old, living in Okinawa, Japan. One hundred eighty five participants (mean age 84.1±3.4 years) assessed in 2011 who were free from frank dementia (defined as Clinical Dementia Ratingâ<1.0) were used for the current cross-sectional study. We examined whether serum omega-3 PUFAs (docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]), arachidonic acid (AA), EPA/AA ratio, DHA/AA ratio, and DHA+EPA are associated with (1) age and (2) global cognitive function (Japanese MMSE) and executive function (Verbal Fluency Letter). Data was analyzed univariately by t-test and multivariately by cumulative logistic regression models controlling for age, gender, years of education, obesity, hypertension, diabetes, and dyslipidemia. RESULTS: Serum DHA levels decreased with increasing age (pâ=â0.04). Higher global cognitive function was associated with higher levels of serum EPA (pâ=â0.03) and DHAâ+âEPA (pâ=â0.03) after controlling for confounders. CONCLUSIONS: Higher serum EPA and DHAâ+âEPA levels were independently associated with better scores on global cognitive function among the oldest old, free from dementia. Longitudinal follow-up studies are warranted.
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Cognición/fisiología , Ácidos Grasos Omega-3/sangre , Factores de Edad , Anciano de 80 o más Años , Ácido Araquidónico/sangre , Análisis Químico de la Sangre , Estudios Transversales , Escolaridad , Femenino , Humanos , Japón/epidemiología , Modelos Logísticos , Masculino , Escala del Estado Mental , Obesidad/sangre , Obesidad/epidemiología , Obesidad/psicología , Estudios Prospectivos , Factores SexualesRESUMEN
Dementia, which dramatically increased in recent years is one of the most important issues in the modern society. Solutions for prevention and management of dementia have not been established. Since hypertension status in middle-age period is known as a risk for the future development of dementia, antihypertensive treatment during such period is important. On the contrary, the influence on the dementia development of hypertension during old-age period has not been clarified yet. Since some reports showed that the antihypertensive treatment prevented the development of dementia, the proper antihypertensive treatment would be considered. It is still unknown that of which kind of antihypertensive drug is most effective for preventing dementia, since clinical trials have not been performed on such hypothesis to be solved. Recent report on the network meta-analysis showed that angiotensin receptor blockers were most effective. Future study should be done for develop the evidence for preventing dementia as a primary endpoint.
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Antihipertensivos/uso terapéutico , Calcio/metabolismo , Cognición/efectos de los fármacos , Demencia/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Animales , Cognición/fisiología , Trastornos del Conocimiento/tratamiento farmacológico , HumanosRESUMEN
An 82-year-old man had a transient ischemic attack (TIA) with symptoms of consciousness disturbance and right hemiparesis while resting in a sitting position after breakfast. His symptoms improved around 1 h after onset when he lied in a supine position and received intravenous hydration. Duplex carotid ultrasonography revealed severe stenosis of the left common carotid artery. A decrease in the brain perfusion reserve was confirmed by acetazolamide-stress brain perfusion scintigraphy. Moreover, ambulatory blood pressure monitoring revealed a reduction in systolic blood pressure below 90 mmHg after each meal, indicating postprandial hypotension (PPH). The PPH was improved by oral administration of α-glucosidase inhibitor without any subsequent recurrences of TIA. The patient was diagnosed with TIA of hemodynamic origin that was induced by PPH and exhibited severe carotid stenosis. PPH is common in elderly people, and it should be recognized as a significant trigger for ischemic cerebrovascular disease.
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Estenosis Carotídea/complicaciones , Ingestión de Alimentos , Hipotensión/complicaciones , Ataque Isquémico Transitorio/etiología , Anciano de 80 o más Años , Humanos , MasculinoRESUMEN
We herein report an unusual case of profound brain infarction of the posterior circulation due to a dolichoectatic vertebrobasilar dissecting aneurysm (DVDA) originating from atherosclerosis. On autopsy, diffuse atherosclerosis was observed with a multi-fusiform aneurysm measuring 1 to 2 cm in diameter ranging from the left vertebral artery to the basilar artery. The microscopic findings of the aneurysm revealed severe stenosis of the artery caused by intimal thickening, intimal flap formation and thrombosis, indicating the presence of a dissecting aneurysm originating from atherosclerosis. The DVDA observed in this case was considered to be slowly progressive and associated with the development of atherosclerosis. The etiology of structural destabilization in patients with DVDA involves rupture of the internal elastic lamina, which is dislodged by massive hematomas that form atheromatous lesions.
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Disección Aórtica/patología , Aterosclerosis/patología , Insuficiencia Vertebrobasilar/patología , Disección Aórtica/etiología , Aterosclerosis/complicaciones , Autopsia , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Vertebrobasilar/etiologíaRESUMEN
BACKGROUND: OX40 is a member of the tumor necrosis factor receptor family that is expressed primarily on activated CD4+ T cells and promotes the development of effector and memory T cells. Although OX40 has been reported to be a target gene of human T-cell leukemia virus type-1 (HTLV-1) viral transactivator Tax and is overexpressed in vivo in adult T-cell leukemia (ATL) cells, an association between OX40 and HTLV-1-associated inflammatory disorders, such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), has not yet been established. Moreover, because abrogation of OX40 signals ameliorates chronic inflammation in animal models of autoimmune disease, novel monoclonal antibodies against OX40 may offer a potential treatment for HTLV-1-associated diseases such as ATL and HAM/TSP. RESULTS: In this study, we showed that OX40 was specifically expressed in CD4+ T cells naturally infected with HTLV-1 that have the potential to produce pro-inflammatory cytokines along with Tax expression. We also showed that OX40 was overexpressed in spinal cord infiltrating mononuclear cells in a clinically progressive HAM/TSP patient with a short duration of illness. The levels of the soluble form of OX40 (sOX40) in the cerebrospinal fluid (CSF) from chronic progressive HAM/TSP patients or from patients with other inflammatory neurological diseases (OINDs) were not different. In contrast, sOX40 levels in the CSF of rapidly progressing HAM/TSP patients were higher than those in the CSF from patients with OINDs, and these patients showed higher sOX40 levels in the CSF than in the plasma. When our newly produced monoclonal antibody against OX40 was added to peripheral blood mononuclear cells in culture, HTLV-1-infected T cells were specifically removed by a mechanism that depends on antibody-dependent cellular cytotoxicity. CONCLUSIONS: Our study identified OX40 as a key molecule and biomarker for rapid progression of HAM/TSP. Furthermore, blocking OX40 may have potential in therapeutic intervention for HAM/TSP.
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Expresión Génica , Virus Linfotrópico T Tipo 1 Humano/patogenicidad , Paraparesia Espástica Tropical/patología , Receptores OX40/análisis , Adulto , Anciano , Anciano de 80 o más Años , Animales , Biomarcadores/líquido cefalorraquídeo , Líquido Cefalorraquídeo/química , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: The purpose of this study was to identify typical clinical characteristics to predict early motor worsening (EMW) of patients with penetrating artery infarction. METHODS: We reviewed 65 consecutive patients with pure motor hemiparesis, sensorimotor stroke, and ataxic hemiparesis. EMW was defined as deterioration by ≥1 point on the National Institutes of Health Stroke Scale for motor function within 5 days of admission. RESULTS: EMW was observed in 22 patients (34%). HbA1c levels were higher in patients with EMW than in those without EMW (7.9 ± 2.6 vs. 6.3 ± 1.6%; p < 0.01). The percentage of EMW patients with intracranial artery stenosis (ICAS) was greater than that of non-EMW patients with ICAS (13/22 patients, 59% vs. 8/43 patients, 19%; p < 0.01). Multivariate logistic regression analysis indicated that HbA1c levels ≥7.0% (OR 3.0, 95% CI 1.5-6.8; p < 0.005) or ICAS (OR 2.3, 95% CI 1.2-4.8; p < 0.05) increased the risk of EMW, and the combination of these factors increased the risk in an additive manner (OR 7.6, 95% CI 2.5-40; p < 0.005). CONCLUSION: HbA1c levels ≥7.0% and/or ICAS in patients with penetrating artery infarction are associated with EMW.
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Infarto Encefálico/complicaciones , Estenosis Carotídea/patología , Hemoglobina Glucada/análisis , Trastornos del Movimiento/etiología , Anciano , Infarto Encefálico/sangre , Infarto Encefálico/patología , Femenino , Humanos , Angiografía por Resonancia Magnética , Imagen por Resonancia Magnética , Masculino , Trastornos del Movimiento/sangre , Trastornos del Movimiento/patologíaRESUMEN
We report on transoral carotid ultrasonography using a micro convex probe with B-flow imaging for determining spontaneous extracranial internal carotid artery dissection just below the petrous portion. A 49-year-old man suffered cortical and subcortical infarction in the region of the right middle cerebral artery. Magnetic resonance angiography on the third day of admission revealed spontaneous recanalization of the right internal carotid artery associated with an intimal flap-like structure at the petrous portion. Transoral carotid ultrasonography using a micro convex probe revealed right extracranial internal carotid artery dissection, showing an increased diameter of the right extracranial internal carotid artery with double lumen formation, stenosis of the true lumen, and a mobile intimal flap in B-flow imaging. Transoral carotid ultrasonography using a micro convex probe was helpful to attempt a self-expanding stent for recanalizing right extracranial internal carotid artery dissection. The patient recovered and was discharged ambulatory. The size of the micro convex probe was optimum for transoral carotid ultrasonography in our patient. Micro convex probe is more commonly used than the standard transoral carotid ultrasonography probe, which lacks versatility. We consider that transoral carotid ultrasonography using a micro convex probe could be routinely used for ultrasonographic evaluation of extracranial internal carotid artery dissection.
Asunto(s)
Disección de la Arteria Carótida Interna/diagnóstico por imagen , Estenosis Carotídea/diagnóstico por imagen , Ultrasonografía Doppler en Color/instrumentación , Disección de la Arteria Carótida Interna/complicaciones , Disección de la Arteria Carótida Interna/terapia , Estenosis Carotídea/complicaciones , Estenosis Carotídea/terapia , Procedimientos Endovasculares/instrumentación , Diseño de Equipo , Humanos , Infarto de la Arteria Cerebral Media/diagnóstico , Infarto de la Arteria Cerebral Media/etiología , Angiografía por Resonancia Magnética , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Stents , Resultado del TratamientoAsunto(s)
Ecocardiografía Transesofágica , Endocarditis no Infecciosa/diagnóstico por imagen , Infarto de la Arteria Cerebral Media/etiología , Adulto , Anticoagulantes/uso terapéutico , Heparina/uso terapéutico , Humanos , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/fisiopatología , Imagen por Resonancia Magnética , Masculino , RecurrenciaRESUMEN
We report a case of a 62-year-old man diagnosed as Crow-Fukase syndrome (POEMS syndrome), in which the serial platelet count and vascular endothelial growth factor (VEGF) concentration were determined before and during the state of disseminated intravascular coagulation (DIC). The serum VEGF concentration was noted to be gradually decreased prior to DIC, after which it abruptly decreased with a corresponding drop in platelet count upon the onset of DIC. The physiological effects of VEGF are viewed as one of the causative factors in DIC and its abrupt and excessive release may have caused the exacerbation of the patient's clinical symptoms.