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BACKGROUND: High doses of glucocorticoids and severe weight loss can cause osteoporosis. We present a case of glucocorticoid-induced osteoporosis and cachexia in an 18-year-old woman who experienced severe appetite loss leading to weight loss, amenorrhea, and multiple thoracolumbar compression fractures. CASE PRESENTATION: The patient had been receiving high-dose glucocorticoid treatment for systemic lupus erythematosus since the age of 13 and developed unexplained appetite loss since the age of 16. She subsequently developed thoracolumbar compression fractures, which necessitated repeated hospitalization. Gradual glucocorticoid tapering using belimumab and weight regain were achieved through high-calorie nutrition administration via the central vein, which helped the patient overcome her cachexic state. Romosozumab administration increased bone mineral density. CONCLUSION: Long-term administration of glucocorticoids may lead to osteoporosis and cachexia, resulting in amenorrhea, especially in young adults. Approaches that taper glucocorticoids and promote weight regain may be helpful in the management of such patients.
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Hydrated nickel hydroxides with partial aluminum substitution were synthesized using the conventional coprecipitation and soft chemistry methods. The soft chemistry derived sample showed better reversibility owing to the low activity for oxygen evolution during charging. Operando X-ray diffraction indicated the increased interlayer distance and decreased crystallinity during discharging caused by water accommodation.
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Introduction: Long-term bisphosphonate (BP) administration may cause an atypical femoral fracture that is occasionally bilateral. We encountered a case of an impending atypical femoral fracture on the contralateral side that progressed to a complete fracture early after surgery for an atypical femoral fracture. Case Report: An 83-year-old woman who had received long-term BP therapy developed a right femoral atypical incomplete fracture that progressed to a complete fracture 5 days after surgery for an atypical complete left femoral fracture. Conclusion: The findings from this case suggest that when an atypical femoral fracture occurs in patients receiving long-term BP therapy, the possibility of an impending atypical femoral fracture on the contralateral side should be considered, and radiographs or CT images should be obtained for both legs. To prevent long-term bed rest in older adults, one- or two-stage bilateral surgery should be considered when imaging reveals bilateral atypical femoral fractures.
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Spontaneous intracerebral hemorrhage (SICH) remains a devastating form of stroke. Prior use of antiplatelets or warfarin before SICH is associated with poor outcomes, but the effects of direct oral anticoagulants (DOACs) remain unclear. This study aimed to clarify trends in prior antithrombotic use and to assess the associations between prior use of antithrombotics and in-hospital mortality using a multicenter prospective registry in Japan. In total, 1085 patients were analyzed. Prior antithrombotic medication included antiplatelets in 14.2%, oral anticoagulants in 8.1%, and both in 1.8%. Prior warfarin use was significantly associated with in-hospital mortality (odds ratio [OR] 5.50, 95% confidence interval [CI] 1.30-23.26, P < 0.05) compared to no prior antithrombotic use. No such association was evident between prior DOAC use and no prior antithrombotic use (OR 1.34, 95% CI 0.44-4.05, P = 0.606). Concomitant use of antiplatelets and warfarin further increased the in-hospital mortality rate (37.5%) compared to warfarin alone (17.2%), but no such association was found for antiplatelets plus DOACs (8.3%) compared to DOACs alone (11.9%). Prior use of warfarin remains an independent risk factor for in-hospital mortality after SICH in the era of DOACs. Further strategies are warranted to reduce SICH among patients receiving oral anticoagulants and to prevent serious outcomes.
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Anticoagulantes , Hemorragia Cerebral , Fibrinolíticos , Mortalidad Hospitalaria , Sistema de Registros , Warfarina , Humanos , Mortalidad Hospitalaria/tendencias , Anciano , Femenino , Masculino , Hemorragia Cerebral/mortalidad , Hemorragia Cerebral/tratamiento farmacológico , Warfarina/uso terapéutico , Warfarina/efectos adversos , Japón/epidemiología , Anciano de 80 o más Años , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Fibrinolíticos/uso terapéutico , Fibrinolíticos/efectos adversos , Persona de Mediana Edad , Factores de Riesgo , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Estudios ProspectivosRESUMEN
Oxyhydrides with multi-anions (O2- and H-) are a recently developed material family and have attracted attention as catalysts and hydride ion conductors. High-pressure and high-temperature reactions are effective in synthesizing oxyhydrides, but the reactions sometimes result in inhomogeneous products due to insufficient diffusion of the solid components. Here, we synthesized new perovskite oxyhydrides SrVO2.4H0.6 and Sr3V2O6.2H0.8. We demonstrated that the addition of SrCl2 flux promotes diffusion during high-pressure and high-temperature reactions, and can be used for selective synthesis of the oxyhydride phases. We conducted in-situ synchrotron X-ray diffraction measurements to reveal the role of this flux and reaction pathways. We also demonstrated the electronic and magnetic properties of the newly synthesized oxyhydrides and that they work as anode materials for Li-ion batteries with excellent reversibility and high-rate characteristics, the first case with an oxyhydride. Our synthesis approach would also be effective in synthesizing various types of multi-component systems.
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OBJECTIVES: To examine the national, 6-year trends in in-hospital clinical outcomes of patients with subarachnoid haemorrhage (SAH) who underwent clipping or coiling and the prognostic influence of temporal trends in the Comprehensive Stroke Center (CSC) capabilities on patient outcomes in Japan. DESIGN: Retrospective study. SETTING: Six hundred and thirty-one primary care institutions in Japan. PARTICIPANTS: Forty-five thousand and eleven patients with SAH who were urgently hospitalised, identified using the J-ASPECT Diagnosis Procedure Combination database. PRIMARY AND SECONDARY OUTCOME MEASURES: Annual number of patients with SAH who remained untreated, or who received clipping or coiling, in-hospital mortality and poor functional outcomes (modified Rankin Scale: 3-6) at discharge. Each CSC was assessed using a validated scoring system (CSC score: 1-25 points). RESULTS: In the overall cohort, in-hospital mortality decreased (year for trend, OR (95% CI): 0.97 (0.96 to 0.99)), while the proportion of poor functional outcomes remained unchanged (1.00 (0.98 to 1.02)). The proportion of patients who underwent clipping gradually decreased from 46.6% to 38.5%, while that of those who received coiling and those left untreated gradually increased from 16.9% to 22.6% and 35.4% to 38%, respectively. In-hospital mortality of coiled (0.94 (0.89 to 0.98)) and untreated (0.93 (0.90 to 0.96)) patients decreased, whereas that of clipped patients remained stable. CSC score improvement was associated with increased use of coiling (per 1-point increase, 1.14 (1.08 to 1.20)) but not with short-term patient outcomes regardless of treatment modality. CONCLUSIONS: The 6-year trends indicated lower in-hospital mortality for patients with SAH (attributable to better outcomes), increased use of coiling and multidisciplinary care for untreated patients. Further increasing CSC capabilities may improve overall outcomes, mainly by increasing the use of coiling. Additional studies are necessary to determine the effect of confounders such as aneurysm complexity on outcomes of clipped patients in the modern endovascular era.
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Procedimientos Endovasculares , Aneurisma Intracraneal , Accidente Cerebrovascular , Hemorragia Subaracnoidea , Humanos , Hemorragia Subaracnoidea/complicaciones , Estudios Retrospectivos , Aneurisma Intracraneal/terapia , Pronóstico , Japón/epidemiología , Resultado del Tratamiento , Accidente Cerebrovascular/complicaciones , Procedimientos Endovasculares/métodosRESUMEN
The effectiveness and safety of intraoperative magnetic resonance imaging (iMRI) are evident from many reports over the past decade. However, these reports have mainly concerned surgeries for glioma and other intra-axial tumours, and applications of this approach for extra-axial tumours are poorly documented. We retrospectively examined three cases in which iMRI was used to assist in the removal of epidermoid cysts. T2-weighted images and diffusion-weighted images were acquired during the surgeries. The value to surgeons of images generated by iMRI, the length of interruption of surgery, and the safety of the patients were assessed. In this study, the images obtained through iMRI provided were clear representations of remnant tumours, even with a low-field system (0.4 Tesla). These images generated enough information to help surgeons decide whether to use an assistance device, such as an endoscope, to remove remnant tumours and whether further retraction of the brain was safe for patients and useful in tumour removal. Intraoperative MRI has long been thought unnecessary for surgery for tumours that are well demarcated and clearly visible under a surgical microscope; in this study, however, intraoperative MRI proved to be useful and safe for patients undergoing epidermoid cyst resection.
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Neoplasias Encefálicas , Quiste Epidérmico , Glioma , Humanos , Quiste Epidérmico/diagnóstico por imagen , Quiste Epidérmico/cirugía , Estudios Retrospectivos , Glioma/cirugía , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/patología , Imagen por Resonancia Magnética/métodosRESUMEN
Objectives: This study aims to investigate the effects of romosozumab on bone mineral density (BMD) and bone metabolism. Methods: In this retrospective case series, romosozumab was administered to 5 premenopausal female patients with osteoporosis and anorexia nervosa with fragility fractures. BMD and bone turnover marker changes were investigated at 6 months and 1 year after administering romosozumab. Results: BMD increased and high-turnover bone metabolism decreased 6 months and 1 year after administering romosozumab. Conclusions: Romosozumab is useful for treating osteoporosis in patients with anorexia nervosa.
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Cobalt-free, nickel-rich positive electrode materials are attracting attention because of their high energy density and low cost, and the ultimate material is LiNiO2 (LNO). One of the issues of LNO is its poor cycling performance, which needs to be improved. Referring to a current study to show the improved stability of single-crystal-like high-nickelate materials, we fabricated single-crystal-like (SC-) LNO and the counterpart polycrystalline (PC-) LNO samples and examined their electrochemical properties. SC-LNO was nearly single-crystal-like, as proved by electron backscattering diffraction, and had more cation mixing than PC-LNO. Cycle tests under 2.5-4.2 V, a 2C rate, and 45 °C conditions showed that the capacity retention of SC-LNO after 500 cycles (63.5%) was significantly better than that of PC-LNO (36.1%) under the same conditions and even better than that of PC-LNO cycled between 2.5 and 4.15 V (50.7%) with the same initial capacity as SC-LNO. The derivative dQ/dV profile of PC-LNO became featureless during a long cycling time, suggesting the progress of cation mixing in PC-LNO, whereas that of SC-LNO was better maintained, in accordance with the serious particle cracking in PC-LNO and no particle cracking found in SC-LNO as the result of post-mortem analysis after 500 cycles. The electrode impedance increase of PC-LNO was considerably larger than that of SC-LNO, corresponding to the formation of rock-salt phases at the surface and the cracked interface of the PC-LNO and the formation of scattered spinel-like phases with a thick cathode electrolyte interphase at the surface of SC-LNO. Accordingly, SC-LNO is shown to be less degraded in both the bulk nature (stable dQ/dV profile and no cracking) and the surface characteristics (high rate capacity maintenance and less impedance increase), suggesting the importance of single-crystal-like particles as durable electrode materials.
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Anterior cervical disc replacement (ACDR) using cervical artificial disc (CAD) has the advantage of maintaining the range of motion (ROM) at the surgical level, subsequently reducing the postoperative risk of adjacent disc disease. Following the approval for the clinical use in Japan, a post-marketing surveillance (PMS) study was conducted for two different types of CAD, namely, Mobi-C (metal-on-plastic design) and Prestige LP (metal-on-metal design). The objective of this prospective observational multicenter study was to analyze the first 2-year surgical results of the PMS study of 1-level ACDR in Japan. A total of 54 patients were registered (Mobi-C, n = 24, MC group; Prestige LP, n = 30, PLP group). Preoperative neurological assessment revealed radiculopathy in 31 patients (57.4%) and myelopathy in 15 patients (27.8%). Preoperative radiological assessment classified the disease category as disc herniation in 15 patients (27.8%), osteophyte in 6 patients (11.1%), and both in 33 patients (61.1%). The postoperative follow-up rates at 6 weeks, 6 months, 1 year, and 2 years after ACDR were 92.6%, 87.0%, 83.3%, and 79.6%, respectively. In both groups, patients' neurological condition improved significantly after surgery. Radiographic assessment revealed loss of mobility at the surgical level in 9.5% of patients in the MC group and in 9.1% of patients in the PLP group. No secondary surgeries at the initial surgical level and no serious adverse events were observed in either group. The present results suggest that 1-level ACDR is safe, although medium- to long-term follow-up is mandatory to further verify the validity of ACDR for Japanese patients.
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Degeneración del Disco Intervertebral , Desplazamiento del Disco Intervertebral , Disco Intervertebral , Fusión Vertebral , Reeemplazo Total de Disco , Humanos , Reeemplazo Total de Disco/efectos adversos , Reeemplazo Total de Disco/métodos , Japón , Desplazamiento del Disco Intervertebral/diagnóstico por imagen , Desplazamiento del Disco Intervertebral/cirugía , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/cirugía , Estudios de Seguimiento , Resultado del Tratamiento , Degeneración del Disco Intervertebral/diagnóstico por imagen , Degeneración del Disco Intervertebral/cirugía , Degeneración del Disco Intervertebral/etiología , Rango del Movimiento Articular , Vigilancia de Productos Comercializados , Discectomía/métodos , Disco Intervertebral/cirugíaRESUMEN
BACKGROUND: Congenital hydrocephalus occurs with some inheritable characteristics, but the mechanisms of its development remain poorly understood. Animal models provide the opportunity to identify potential genetic causes in this condition. The Hydrocephalus-Texas (H-Tx) rat strain is one of the most studied animal models for investigating the causative genetic alterations and analyzing downstream pathogenetic mechanisms of congenital hydrocephalus. METHODS: Comparative genomic hybridization (CGH) array on non-hydrocephalic and hydrocephalic H-Tx rats was used to identify causative genes of hydrocephalus. Targeted gene knockout mice were generated by CRISPR/Cas9 to study the role of this gene in hydrocephalus. RESULTS: CGH array revealed a copy number loss in chromosome 16p16 region in hydrocephalic H-Tx rats at 18 days gestation, encompassing the protein tyrosine phosphatase non-receptor type 20 (Ptpn20), a non-receptor tyrosine phosphatase, without change in most non-hydrocephalic H-Tx rats. Ptpn20-knockout (Ptpn20-/-) mice were generated and found to develop ventriculomegaly at 8 weeks. Furthermore, high expression of phosphorylated Na-K-Cl cotransporter 1 (pNKCC1) was identified in the choroid plexus (CP) epithelium of mice lacking Ptpn20 from 8 weeks until 72 weeks. CONCLUSIONS: This study determined the chromosomal location of the hydrocephalus-associated Ptpn20 gene in hydrocephalic H-Tx rats. The high level of pNKCC1 mediated by Ptpn20 deletion in CP epithelium may cause overproduction of cerebrospinal fluid and contribute to the formation of hydrocephalus in Ptpn20-/- mice. Ptpn20 may be a potential therapeutic target in the treatment of hydrocephalus.
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Plexo Coroideo , Hidrocefalia , Miembro 2 de la Familia de Transportadores de Soluto 12/metabolismo , Animales , Plexo Coroideo/metabolismo , Hibridación Genómica Comparativa , Hidrocefalia/líquido cefalorraquídeo , Ratones , Monoéster Fosfórico Hidrolasas/metabolismo , Fosforilación , Ratas , Miembro 2 de la Familia de Transportadores de Soluto 12/genética , TexasRESUMEN
To determine whether increasing thrombectomy-capable hospitals with moderate comprehensive stroke center (CSC) capabilities is a valid alternative to centralization of those with high CSC capabilities. This retrospective, nationwide, observational study used data from the J-ASPECT database linked to national emergency medical service (EMS) records, captured during 2013-2016. We compared the influence of mechanical thrombectomy (MT) use, the CSC score, and the total EMS response time on the modified Rankin Scale score at discharge among patients with acute ischemic stroke transported by ambulance, in phases I (2013-2014, 1461 patients) and II (2015-2016, 3259 patients). We used ordinal logistic regression analyses to analyze outcomes. From phase I to II, MTs increased from 2.7 to 5.5%, and full-time endovascular physicians per hospital decreased. The CSC score and EMS response time remained unchanged. In phase I, higher CSC scores were associated with better outcomes (1-point increase, odds ratio [95% confidence interval]: 0.951 [0.915-0.989]) and longer EMS response time was associated with worse outcomes (1-min increase, 1.007 [1.001-1.013]). In phase II, neither influenced the outcomes. During the transitional shortage of thrombectomy-capable hospitals, increasing hospitals with moderate CSC scores may increase nationwide access to MT, improving outcomes.
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Isquemia Encefálica , Servicios Médicos de Urgencia , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Hospitales , Humanos , Japón , Estudios Retrospectivos , Accidente Cerebrovascular/cirugía , Trombectomía , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: In previous studies, women had a higher risk of rupture of intracranial aneurysms than men, but female sex was not an independent risk factor. This may be explained by a higher prevalence of patient- or aneurysm-related risk factors for rupture in women than in men or by insufficient power of previous studies. We assessed sex differences in rupture rate taking into account other patient- and aneurysm-related risk factors for aneurysmal rupture. METHODS: We searched Embase and Pubmed for articles published until December 1, 2020. Cohorts with available individual patient data were included in our meta-analysis. We compared rupture rates of women versus men using a Cox proportional hazard regression model adjusted for the PHASES score (Population, Hypertension, Age, Size of Aneurysm, Earlier Subarachnoid Hemorrhage From Another Aneurysm, Site of Aneurysm), smoking, and a positive family history of aneurysmal subarachnoid hemorrhage. RESULTS: We pooled individual patient data from 9 cohorts totaling 9940 patients (6555 women, 66%) with 12 193 unruptured intracranial aneurysms, and 24 357 person-years follow-up. Rupture occurred in 163 women (rupture rate 1.04%/person-years [95% CI, 0.89-1.21]) and 63 men (rupture rate 0.74%/person-years [95% CI, 0.58-0.94]). Women were older (61.9 versus 59.5 years), were less often smokers (20% versus 44%), more often had internal carotid artery aneurysms (24% versus 17%), and larger sized aneurysms (≥7 mm, 24% versus 23%) than men. The unadjusted women-to-men hazard ratio was 1.43 (95% CI, 1.07-1.93) and the adjusted women/men ratio was 1.39 (95% CI, 1.02-1.90). CONCLUSIONS: Women have a higher risk of aneurysmal rupture than men and this sex difference is not explained by differences in patient- and aneurysm-related risk factors for aneurysmal rupture. Future studies should focus on the factors explaining the higher risk of aneurysmal rupture in women.
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Aneurisma Roto/epidemiología , Aneurisma Intracraneal/complicaciones , Aneurisma Intracraneal/epidemiología , Factores de Edad , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Factores Sexuales , Fumar/epidemiología , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/epidemiologíaRESUMEN
Each year, the Japan Neurosurgical Society (JNS) reports up-to-date statistics from the Japan Neurosurgical Database regarding case volume, patient demographics, and in-hospital outcomes of the overall cohort and neurosurgical subgroup according to the major classifications of main diagnosis. We hereby report patient demographics, in-hospital mortality, length of hospital stay, purpose of admission, number of medical management, direct surgery, endovascular treatment, and radiosurgery of the patients based on the major classifications and/or main diagnosis registered in 2018 and 2019 in the overall cohort (523283 and 571143 patients, respectively) and neurosurgical subgroup (177184 and 191595 patients, respectively). The patient demographics, disease severity, proportion of purpose of admission (e.g., operation, 33.9-33.5%) and emergent admission (68.4-67.8%), and in-hospital mortality (e.g., cerebrovascular diseases, 6.3-6.5%; brain tumor, 3.1-3%; and neurotrauma, 4.3%) in the overall cohort were comparable between 2018 and 2019. In total, 207783 and 225217 neurosurgical procedures were performed in the neurosurgical subgroup in 2018 and 2019, respectively, of which endovascular treatment comprised 19.1% and 20.3%, respectively. Neurosurgical management of chronic subdural hematoma (19.4-18.9%) and cerebral aneurysm (15.4-14.8%) was most common. Notably, the proportion of management of ischemic stroke/transient ischemic attack, including recombinant tissue plasminogen activator infusion and endovascular acute reperfusion therapy, increased from 7.5% in 2018 to 8.8% in 2019. The JNS statistical update represents a critical resource for the lay public, policy makers, media professionals, neurosurgeons, healthcare administrators, researchers, health advocates, and others seeking the best available data on neurosurgical practice.
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Aneurisma Intracraneal , Accidente Cerebrovascular , Humanos , Japón/epidemiología , Procedimientos Neuroquirúrgicos , Activador de Tejido PlasminógenoRESUMEN
BACKGROUND AND OBJECTIVES: We combined individual patient data (IPD) from prospective cohorts of patients with unruptured intracranial aneurysms (UIAs) to assess to what extent patients with familial UIA have a higher rupture risk than those with sporadic UIA. METHODS: For this IPD meta-analysis, we performed an Embase and PubMed search for studies published up to December 1, 2020. We included studies that (1) had a prospective study design; (2) included 50 or more patients with UIA; (3) studied the natural course of UIA and risk factors for aneurysm rupture including family history for aneurysmal subarachnoid haemorrhage and UIA; and (4) had aneurysm rupture as an outcome. Cohorts with available IPD were included. All studies included patients with newly diagnosed UIA visiting one of the study centers. The primary outcome was aneurysmal rupture. Patients with polycystic kidney disease and moyamoya disease were excluded. We compared rupture rates of familial vs sporadic UIA using a Cox proportional hazard regression model adjusted for PHASES score and smoking. We performed 2 analyses: (1) only studies defining first-degree relatives as parents, children, and siblings and (2) all studies, including those in which first-degree relatives are defined as only parents and children, but not siblings. RESULTS: We pooled IPD from 8 cohorts with a low and moderate risk of bias. First-degree relatives were defined as parents, siblings, and children in 6 cohorts (29% Dutch, 55% Finnish, 15% Japanese), totaling 2,297 patients (17% familial, 399 patients) with 3,089 UIAs and 7,301 person-years follow-up. Rupture occurred in 10 familial cases (rupture rate: 0.89%/person-year; 95% confidence interval [CI] 0.45-1.59) and 41 sporadic cases (0.66%/person-year; 95% CI 0.48-0.89); adjusted hazard ratio (HR) for familial cases 2.56 (95% CI 1.18-5.56). After adding the 2 cohorts excluding siblings as first-degree relatives, resulting in 9,511 patients, the adjusted HR was 1.44 (95% CI 0.86-2.40). DISCUSSION: The risk of rupture of UIA is 2.5 times higher, with a range from a 1.2 to 5 times higher risk, in familial than in sporadic UIA. When assessing the risk of rupture in UIA, family history should be taken into account.
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Aneurisma Roto , Aneurisma Intracraneal , Hemorragia Subaracnoidea , Aneurisma Roto/epidemiología , Niño , Humanos , Aneurisma Intracraneal/diagnóstico , Aneurisma Intracraneal/epidemiología , Aneurisma Intracraneal/genética , Estudios Prospectivos , Factores de Riesgo , Hemorragia Subaracnoidea/epidemiología , Hemorragia Subaracnoidea/genéticaRESUMEN
Glycosylation is a cell type-specific post-translational modification that can be used for biomarker identification in various diseases. Aim of this study is to explore glycan-biomarkers on transferrin (Tf) for Alzheimer's disease (AD) in cerebrospinal fluid (CSF). Glycan structures of CSF Tf were analyzed by ultra-performance liquid chromatography followed by mass spectrometry. We found that a unique mannosylated-glycan is carried by a Tf isoform in CSF (Man-Tf). The cerebral cortex contained Man-Tf as a major isofom, suggesting that CSF Man-Tf is, at least partly, derived from the cortex. Man-Tf levels were analyzed in CSF of patients with neurological diseases. Concentrations of Man-Tf were significantly increased in AD and mild cognitive impairment (MCI) comparing with other neurological diseases, and the levels correlated well with those of phosphorylated-tau (p-tau), a representative AD marker. Consistent with the observation, p-tau and Tf were co-expressed in hippocampal neurons of AD, leading to the notion that a combined p-tau and Man-Tf measure could be a biomarker for AD. Indeed, levels of p-tau x Man-Tf showed high diagnostic accuracy for MCI and AD; 84% sensitivities and 90% specificities for MCI and 94% sensitivities and 89% specificities for AD. Thus Man-Tf could be a new biomarker for AD.
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Idiopathic normal pressure hydrocephalus (iNPH) is a condition resulting from impaired cerebrospinal fluid (CSF) absorption and excretion characterized by a triad of symptoms comprising dementia, gait disturbance (impaired trunk balance), and urinary incontinence. CSF biomarkers not only assist in diagnosis but are also important for analyzing the pathology and understanding appropriate treatment indications. As the neuropathological findings characteristic of iNPH have yet to be defined, there remains no method to diagnose iNPH with 100% sensitivity and specificity. Neurotoxic proteins are assumed to be involved in the neurological symptoms of iNPH, particularly the appearance of cognitive impairment. The symptoms of iNPH can be reversed by improving CSF turnover through shunting. However, early diagnosis is essential as once neurodegeneration has progressed, pathological changes become irreversible and symptom improvement is minimal, even after shunting. Combining a variety of diagnostic methods may lead to a more definitive diagnosis and accurate prediction of the prognosis following shunt treatment. Identifying comorbidities in iNPH using CSF biomarkers does not contraindicate shunting-based intervention, but does limit the improvement in symptoms it yields, and provides vital information for predicting post-treatment prognosis.
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Hidrocéfalo Normotenso , Biomarcadores , Derivaciones del Líquido Cefalorraquídeo , Diagnóstico Precoz , Humanos , Hidrocéfalo Normotenso/diagnóstico , Hidrocéfalo Normotenso/epidemiología , Hidrocéfalo Normotenso/cirugía , PronósticoRESUMEN
Spontaneous intracranial hypotension (SIH) is caused by cerebrospinal fluid (CSF) leakage. Patients with SIH experience postural headaches, nausea, etc., due to CSF hypovolemia. Imaging studies and clinical examinations, such as radioisotope (RI) scintigraphy, are useful for diagnosing SIH. However, 20-30% of patients do not show typical morphology and clinical test results. We previously reported that CSF contains transferrin (Tf) isoforms:"brain-type" Tf derived from the choroid plexus and "serum-type" Tf derived from blood. We showed that both isoforms increased in the CSF of patients with SIH by Western blotting. In the present study, we demonstrate that conventional ELISA for quantifying total Tf is useful for diagnosing SIH more accurately than Western blotting. In addition, SIH with chronic subdural hematoma (CSDH) was also accurately diagnosed.ãTotal Tf in the CSF can serve as a useful biomarker for diagnosing SIH with or without CSDH.
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Hipotensión Intracraneal , Biomarcadores , Encéfalo , Pérdida de Líquido Cefalorraquídeo/diagnóstico , Humanos , Hipotensión Intracraneal/diagnóstico , TransferrinaRESUMEN
BACKGROUND: The amyloid-ß oligomers, consisting of 10-20 monomers (AßO10-20), have strong neurotoxicity and are associated with cognitive impairment in Alzheimer's disease (AD). However, their role in patients with idiopathic normal pressure hydrocephalus (iNPH) is poorly understood. OBJECTIVE: We hypothesized that cerebrospinal fluid (CSF) AßO10-20 accumulates in patients with iNPH, and its clearance after CSF shunting contributes to neurological improvement. We measured CSF AßO10-20 levels before and after CSF shunting in iNPH patients evaluating their diagnostic and prognostic role. METHODS: We evaluated two iNPH cohorts: "evaluation" (cohort-1) with 32 patients and "validation" (cohort-2) with 13 patients. Comparison cohorts included: 27 neurologically healthy controls (HCs), and 16 AD, 15 Parkinson's disease (PD), and 14 progressive supranuclear palsy (PSP) patients. We assessed for all cohorts CSF AßO10-20 levels and their comprehensive clinical data. iNPH cohort-1 pre-shunting data were compared with those of comparison cohorts, using cohort-2 for validation. Next, we compared cohort-1's clinical and CSF data: 1) before and after CSF shunting, and 2) increased versus decreased AßO10-20 levels at baseline, 1 and 3 years after shunting. RESULTS: Cohort-1 had higher CSF AßO10-20 levels than the HCs, PD, and PSP cohorts. This result was validated with data from cohort-2. CSF AßO10-20 levels differentiated cohort-1 from the PD and PSP groups, with an area under receiver operating characteristic curve of 0.94. AßO10-20 levels in cohort-1 decreased after CSF shunting. Patients with AßO10-20 decrease showed better cognitive outcome than those without. CONCLUSION: AßO10-20 accumulates in patients with iNPH and is eliminated by CSF shunting. AßO10-20 can be an applicable diagnostic and prognostic biomarker.