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BACKGROUND: During gynecological laparoscopic surgery, pneumoperitoneum and the Trendelenburg position (TP) can lead to increased intracranial pressure (ICP). However, it remains unclear whether perioperative fluid therapy impacts ICP. The purpose of this research was to evaluate the impact of restrictive fluid (RF) therapy versus conventional fluid (CF) therapy on ICP in gynecological laparoscopic surgery patients by measuring the ratio of the optic nerve sheath diameter (ONSD) to the eyeball transverse diameter (ETD) using ultrasound. METHODS: Sixty-four patients who were scheduled for laparoscopic gynecological surgery were randomly assigned to the CF group or the RF group. The main outcomes were differences in the ONSD/ETD ratios between the groups at predetermined time points. The secondary outcomes were intraoperative circulatory parameters (including mean arterial pressure, heart rate, and urine volume changes) and postoperative recovery indicators (including extubation time, length of post-anaesthesia care unit stay, postoperative complications, and length of hospital stay). RESULTS: There were no statistically significant differences in the ONSD/ETD ratio and the ONSD over time between the two groups (all p > 0.05). From T2 to T4, the ONSD/ETD ratio and the ONSD in both groups were higher than T1 (all p < 0.001). From T1 to T2, the ONSD/ETD ratio in both groups increased by 14.3%. However, the extubation time in the RF group was shorter than in the CF group [median difference (95% CI) -11(-21 to -2) min, p = 0.027]. There were no differences in the other secondary outcomes. CONCLUSION: In patients undergoing laparoscopic gynecological surgery, RF did not significantly lower the ONSD/ETD ratio but did shorten the tracheal extubation time, when compared to CF. TRIAL REGISTRATION: ChiCTR2300079284. Registered on December 29, 2023.
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Fluidoterapia , Procedimientos Quirúrgicos Ginecológicos , Presión Intracraneal , Laparoscopía , Nervio Óptico , Ultrasonografía , Humanos , Femenino , Laparoscopía/métodos , Nervio Óptico/diagnóstico por imagen , Adulto , Procedimientos Quirúrgicos Ginecológicos/métodos , Presión Intracraneal/fisiología , Fluidoterapia/métodos , Ultrasonografía/métodos , Persona de Mediana Edad , Inclinación de Cabeza , Ojo , Estudios Prospectivos , Hipertensión Intracraneal/etiología , Hipertensión Intracraneal/diagnóstico por imagen , Complicaciones Posoperatorias/prevención & controlRESUMEN
BACKGROUND: During laparoscopic hysterectomy (LH), the elevation of intra-abdominal and intra-thoracic pressures due to pneumoperitoneum (PP) results in an increase in intracranial pressure (ICP). The Trendelenburg position (TP) is an accentuating factor. This trial aimed to assess the effect of intravenous (IV) lidocaine infusion on optic nerve sheath diameter (ONSD), a widely accepted surrogate measure for ICP, during PP and TP. METHODS: A randomized, placebo-controlled study was conducted on 66 patients scheduled for LH, equally divided into a lidocaine group and a saline group. ONSD, the primary outcome, was recorded before induction (T1), before PP initiation in the supine position (T2), five minutes (T3), 30 minutes (T4), and 60 minutes (T5) after PP and TP, and five minutes after termination of PP in the supine position (T6). Secondary outcomes included numerical rating scale (NRS) scores at arrival to the post-anesthesia care unit (PACU), 6, 12, and 24 hours after surgery, and postoperative adverse effects. RESULTS: ONSD at T4 and T5 was significantly lower in the lidocaine group than in the saline group (T4: 4.94±0.43 mm vs. 5.27±0.37 mm; P =0.003, T5: 5.08±0.46 vs. 5.41±0.38 mm; P =0.004). The lidocaine group had significantly lower NRS values than the saline group only at PACU arrival (median [Q1-Q3]: 5 [4-6] vs. 6 [5-6.25]; P =0.016). Fewer patients in the lidocaine group experienced postoperative headache (P =0.029). CONCLUSIONS: IV lidocaine during LH can attenuate the ONSD distension, decrease pain scores at PACU arrival, and reduce the incidence of postoperative headache.
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Anestésicos Locales , Histerectomía , Laparoscopía , Lidocaína , Nervio Óptico , Humanos , Femenino , Lidocaína/administración & dosificación , Persona de Mediana Edad , Nervio Óptico/efectos de los fármacos , Anestésicos Locales/administración & dosificación , Adulto , Infusiones Intravenosas , Inclinación de Cabeza , Método Doble Ciego , Presión Intracraneal/efectos de los fármacosRESUMEN
A 72-year-old woman with relapsed FLT3-ITD-positive acute myeloid leukemia was treated with gilteritinib and achieved complete remission with incomplete hematological recovery. However, two months later, she developed optic nerve infiltration and lost vision in her right eye while maintaining hematological remission on gilteritinib. Intrathecal injection of cytotoxic drugs reduced the number of blasts in the cerebrospinal fluid (CSF), but her vision did not recover. At the onset of optic nerve infiltration, at a dose of 80 mg/day gilteritinib, the plasma trough and CSF levels of gilteritinib were 151.9 ng/ml and 1.9 ng/ml, respectively, with a central nervous system (CNS) penetration rate of 1.3%. Hematologic progressive disease (PD) was detected after 40 days, and the patient died one month later. Target sequencing at the time of hematologic PD revealed the FLT3 F691L mutation, which is known to confer resistance to gilteritinib. In this patient, pharmacokinetic (low CNS penetration of gilteritinib) and pharmacodynamic (acquisition of a drug resistance mutation) mechanisms were thought to be responsible for the CNS relapse and hematologic PD, respectively. We believe this is a valuable case to report considering the scarcity of data on CNS penetration of FLT3 inhibitors and their effects on CNS disease in the literature.
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Compuestos de Anilina , Leucemia Mieloide Aguda , Pirazinas , Recurrencia , Tirosina Quinasa 3 Similar a fms , Humanos , Tirosina Quinasa 3 Similar a fms/genética , Leucemia Mieloide Aguda/tratamiento farmacológico , Pirazinas/administración & dosificación , Pirazinas/uso terapéutico , Anciano , Femenino , Compuestos de Anilina/uso terapéutico , Compuestos de Anilina/administración & dosificación , Tiofenos/administración & dosificación , Tiofenos/uso terapéutico , Nervio Óptico/patología , Mutación , Resultado FatalRESUMEN
Experimental autoimmune encephalomyelitis is a demyelinating disease that causes paralysis in laboratory rats. This condition lacks treatment that reverses damage to the myelin sheaths of neuronal cells. Therefore, in this study, treatment with EPO as a neuroprotective effect was established to evaluate the ERK 1/2 signaling pathway and its participation in the EAE model. EPO was administered in 5000 U/Kg Sprague Dawley rats. U0126 was used as an inhibitor of the ERK 1/2 pathway to demonstrate the possible activation of this pathway in the model. Spinal cord and optic nerve tissues were evaluated using staining techniques such as H&E and the Luxol Fast Blue myelin-specific technique, as well as immunohistochemistry of the ERK 1/2 protein. The EPO-treated groups showed a decrease in cellular sampling in the spinal cord tissues but mainly in the optic nerve, as well as an increase in the expression of the ERK 1/2 protein in both tissues. The findings of this study suggest that EPO treatment reduces cellular death in EAE-induced rats by regulating the ERK pathway.
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Encefalomielitis Autoinmune Experimental , Eritropoyetina , Sistema de Señalización de MAP Quinasas , Fármacos Neuroprotectores , Nervio Óptico , Ratas Sprague-Dawley , Médula Espinal , Animales , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/metabolismo , Encefalomielitis Autoinmune Experimental/patología , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Eritropoyetina/farmacología , Nervio Óptico/efectos de los fármacos , Nervio Óptico/patología , Nervio Óptico/metabolismo , Ratas , Médula Espinal/metabolismo , Médula Espinal/efectos de los fármacos , Médula Espinal/patología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Femenino , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Proteína Quinasa 1 Activada por Mitógenos/metabolismoRESUMEN
As the primary connection between the eye and brain, the optic nerve plays a pivotal role in visual information transmission. Injuries to the optic nerve can occur for various reasons, including trauma, glaucoma, and neurodegenerative diseases. Retinal ganglion cells (RGCs), a type of neurons that extend axons through the optic nerve, can rapidly respond to injury and initiate cell death. Additionally, following optic nerve injury microglia, which serve as markers of neuroinflammation, transition from a resting state to an activated state. The phosphorylation of collapsin response mediator protein2 (CRMP2) in the semaphorin 3A (Sema3A) signalling pathway affects several processes, including axon guidance and neuron regeneration. In this study, we used an optic nerve crush (ONC) mouse model to investigate the effects of suppressing CRMP2 phosphorylation on microglia activation. We found that CRMP2 phosphorylation inhibitor suppressed RGCs loss and promoted neuronal regeneration following ONC. In addition, CRMP2 S522A mutant (CRMP2 KI) mice exhibited decreased microglial activation in both the retina and optic nerve following ONC. These results suggest that inhibiting the phosphorylation of CRMP2 can alleviate the loss of RGCs and microglial activation after optic nerve injury, providing insight into the development of treatments for optical neuropathies and neurodegenerative diseases.
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Péptidos y Proteínas de Señalización Intercelular , Microglía , Regeneración Nerviosa , Proteínas del Tejido Nervioso , Traumatismos del Nervio Óptico , Nervio Óptico , Retina , Células Ganglionares de la Retina , Semaforina-3A , Animales , Traumatismos del Nervio Óptico/fisiopatología , Traumatismos del Nervio Óptico/metabolismo , Traumatismos del Nervio Óptico/tratamiento farmacológico , Microglía/metabolismo , Microglía/efectos de los fármacos , Fosforilación , Ratones , Regeneración Nerviosa/efectos de los fármacos , Péptidos y Proteínas de Señalización Intercelular/genética , Proteínas del Tejido Nervioso/genética , Células Ganglionares de la Retina/efectos de los fármacos , Células Ganglionares de la Retina/metabolismo , Nervio Óptico/metabolismo , Semaforina-3A/genética , Semaforina-3A/metabolismo , Retina/efectos de los fármacos , Retina/metabolismo , Compresión Nerviosa , Ratones Endogámicos C57BL , Masculino , Modelos Animales de Enfermedad , Ratones TransgénicosRESUMEN
Wolfram syndrome (WS) is a rare childhood disease characterized by diabetes mellitus, diabetes insipidus, blindness, deafness, neurodegeneration and eventually early death, due to autosomal recessive mutations in the WFS1 (and WFS2) gene. While it is categorized as a neurodegenerative disease, it is increasingly becoming clear that other cell types besides neurons may be affected and contribute to the pathogenesis. MRI studies in patients and phenotyping studies in WS rodent models indicate white matter/myelin loss, implicating a role for oligodendroglia in WS-associated neurodegeneration. In this study, we sought to determine if oligodendroglia are affected in WS and whether their dysfunction may be the primary cause of the observed optic neuropathy and brain neurodegeneration. We demonstrate that 7.5-month-old Wfs1∆exon8 mice display signs of abnormal myelination and a reduced number of oligodendrocyte precursor cells (OPCs) as well as abnormal axonal conduction in the optic nerve. An MRI study of the brain furthermore revealed grey and white matter loss in the cerebellum, brainstem, and superior colliculus, as is seen in WS patients. To further dissect the role of oligodendroglia in WS, we performed a transcriptomics study of WS patient iPSC-derived OPCs and pre-myelinating oligodendrocytes. Transcriptional changes compared to isogenic control cells were found for genes with a role in ER function. However, a deep phenotyping study of these WS patient iPSC-derived oligodendroglia unveiled normal differentiation, mitochondria-associated endoplasmic reticulum (ER) membrane interactions and mitochondrial function, and no overt signs of ER stress. Overall, the current study indicates that oligodendroglia functions are largely preserved in the WS mouse and patient iPSC-derived models used in this study. These findings do not support a major defect in oligodendroglia function as the primary cause of WS, and warrant further investigation of neurons and neuron-oligodendroglia interactions as a target for future neuroprotective or -restorative treatments for WS.
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Células Madre Pluripotentes Inducidas , Oligodendroglía , Fenotipo , Síndrome de Wolfram , Animales , Células Madre Pluripotentes Inducidas/patología , Síndrome de Wolfram/patología , Síndrome de Wolfram/genética , Oligodendroglía/patología , Ratones , Humanos , Modelos Animales de Enfermedad , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Masculino , Nervio Óptico/patología , Ratones Endogámicos C57BL , FemeninoRESUMEN
Fish retinal ganglion cells (RGCs) can regenerate after optic nerve lesions (ONLs). We previously reported that heat shock factor 1 (HSF1) and Yamanaka factors increased in the zebrafish retina 0.5-24 h after ONLs, and they led to cell survival and the transformation of neuro-stem cells. We also showed that retinoic acid (RA) signaling and transglutaminase 2 (TG2) were activated in the fish retina, performing neurite outgrowth 5-30 days after ONLs. In this study, we found that RA signaling and TG2 increased within 0.5 h in the zebrafish retina after ONLs. We examined their interaction with the TG2-specific morpholino and inhibitor due to the significantly close initiation time of TG2 and HSF1. The inhibition of TG2 led to the complete suppression of HSF1 expression. Furthermore, the results of a ChIP assay with an anti-TG2 antibody evidenced significant anti-TG2 immunoprecipitation of HSF1 genome DNA after ONLs. The inhibition of TG2 also suppressed Yamanaka factors' gene expression. This rapid increase in TG2 expression occurred 30 min after the ONLs, and RA signaling occurred 15 min before this change. The present study demonstrates that TG2 regulates Yamanaka factors via HSF1 signals in the acute phase of fish optic nerve regeneration.
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Factores de Transcripción del Choque Térmico , Regeneración Nerviosa , Nervio Óptico , Proteína Glutamina Gamma Glutamiltransferasa 2 , Transglutaminasas , Pez Cebra , Animales , Pez Cebra/genética , Proteína Glutamina Gamma Glutamiltransferasa 2/metabolismo , Transglutaminasas/genética , Transglutaminasas/metabolismo , Regeneración Nerviosa/genética , Nervio Óptico/metabolismo , Factores de Transcripción del Choque Térmico/metabolismo , Factores de Transcripción del Choque Térmico/genética , Tretinoina/farmacología , Tretinoina/metabolismo , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo , Proteínas de Unión al GTP/metabolismo , Proteínas de Unión al GTP/genética , Células Ganglionares de la Retina/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Traumatismos del Nervio Óptico/metabolismo , Traumatismos del Nervio Óptico/genética , Transducción de SeñalRESUMEN
Glaucoma is a neurodegenerative disease affecting millions worldwide, characterised by retinal ganglion cell (RGC) degeneration which leads to blindness in more advanced cases. Although the pathogenesis and underlying mechanisms of glaucoma are not fully understood, there are theories that hint at demyelination playing a role in the disease process. Demyelination, or the degeneration of the myelin sheath surrounding axons, has been found in previous studies using animal models of glaucoma and clinical assessments of glaucoma patients. However, this has not been fully realised or quantified in glaucoma patients. Utilising postmortem optic nerve samples from glaucoma and healthy subjects, various immunohistochemical and morphological assessments were performed to determine the extent, if any, of demyelination in glaucomatous optic nerves. Our findings revealed that alongside nerve shrinkage and degeneration of nerve tissue fascicles, there were significantly less myelin proteins, specifically myelin basic protein (MBP), in glaucoma optic nerves. Additionally, the loss of MBP was correlated with decreased oligodendrocyte (OLG) precursors and increasing glial activity. This further supports previous evidence that demyelination may be a secondary degenerative process associated with glaucoma disease progression. Not only do these results provide evidence for potential disease mechanisms, but this is also the first study to quantify optic nerve demyelination in glaucoma postmortem tissue.
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Enfermedades Desmielinizantes , Glaucoma , Nervio Óptico , Humanos , Nervio Óptico/patología , Glaucoma/patología , Glaucoma/metabolismo , Anciano , Masculino , Femenino , Enfermedades Desmielinizantes/patología , Persona de Mediana Edad , Autopsia , Anciano de 80 o más Años , Proteína Básica de Mielina/metabolismo , Células Ganglionares de la Retina/patología , Vaina de Mielina/patologíaRESUMEN
Purpose: Experimental autoimmune encephalomyelitis (EAE) scoring, the most commonly used primary outcome metric for an in vivo model of multiple sclerosis (MS), is highly variable and subjective. Here we explored the use of visual biomarkers in EAE as more objective and clinically relevant primary outcomes. Methods: Motor impairment in myelin oligodendrocyte glycoprotein-immunized C57BL/6J mice was quantified using a five-point EAE grading scale. Pattern electroretinography (pERG) and retinal ganglion cell/inner plexiform layer (RGC/IPL) complex thickness were measured 60 days after induction. Optic nerve histopathology was analyzed at endpoint. Results: EAE mice displayed motor impairments ranging from mild to severe. Significant correlations were seen between pERG amplitude and last EAE score, mean EAE score, and cumulative EAE score. Optical coherence tomography (OCT) analysis demonstrated a significant correlation between thinning of the RGC/IPL complex and both EAE score and pERG amplitude. Optic nerve histopathology showed significant correlations between demyelination and cumulative EAE score, pERG amplitude, and RGC/IPL complex thickness, as well as between immune cell infiltration and cumulative EAE score, pERG amplitude, and RGC/IPL complex thickness in EAE mice. Conclusions: Unlike EAE scoring, pERG and OCT show direct measurement of retinal structure and function. Therefore we conclude that visual outcomes are well suited as a direct assessment of optic nerve involvement in this EAE model of MS while also being indicative of motor impairment. Translational Relevance: Standardizing directly translatable measurements as primary outcome parameters in the murine EAE model could lead to more rapid and relevant testing of new therapeutic approaches for mitigating MS.
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Biomarcadores , Electrorretinografía , Encefalomielitis Autoinmune Experimental , Ratones Endogámicos C57BL , Neuritis Óptica , Células Ganglionares de la Retina , Tomografía de Coherencia Óptica , Animales , Encefalomielitis Autoinmune Experimental/patología , Encefalomielitis Autoinmune Experimental/fisiopatología , Neuritis Óptica/patología , Neuritis Óptica/fisiopatología , Neuritis Óptica/inmunología , Ratones , Femenino , Electrorretinografía/métodos , Células Ganglionares de la Retina/patología , Nervio Óptico/patología , Glicoproteína Mielina-Oligodendrócito/inmunología , Modelos Animales de EnfermedadRESUMEN
OBJECTIVE: This study aimed to develop and test a model for predicting dysthyroid optic neuropathy (DON) based on clinical factors and imaging markers of the optic nerve and cerebrospinal fluid (CSF) in the optic nerve sheath. METHODS: This retrospective study included patients with thyroid-associated ophthalmopathy (TAO) without DON and patients with TAO accompanied by DON at our hospital. The imaging markers of the optic nerve and CSF in the optic nerve sheath were measured on the water-fat images of each patient and, together with clinical factors, were screened by Least absolute shrinkage and selection operator. Subsequently, we constructed a prediction model using multivariate logistic regression. The accuracy of the model was verified using receiver operating characteristic curve analysis. RESULTS: In total, 80 orbits from 44 DON patients and 90 orbits from 45 TAO patients were included in our study. Two variables (optic nerve subarachnoid space and the volume of the CSF in the optic nerve sheath) were found to be independent predictive factors and were included in the prediction model. In the development cohort, the mean area under the curve (AUC) was 0.994, with a sensitivity of 0.944, specificity of 0.967, and accuracy of 0.901. Moreover, in the validation cohort, the AUC was 0.960, the sensitivity was 0.889, the specificity was 0.893, and the accuracy was 0.890. CONCLUSIONS: A combined model was developed using imaging data of the optic nerve and CSF in the optic nerve sheath, serving as a noninvasive potential tool to predict DON.
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Oftalmopatía de Graves , Enfermedades del Nervio Óptico , Nervio Óptico , Humanos , Masculino , Femenino , Persona de Mediana Edad , Nervio Óptico/diagnóstico por imagen , Nervio Óptico/patología , Oftalmopatía de Graves/líquido cefalorraquídeo , Oftalmopatía de Graves/diagnóstico por imagen , Enfermedades del Nervio Óptico/diagnóstico por imagen , Enfermedades del Nervio Óptico/líquido cefalorraquídeo , Enfermedades del Nervio Óptico/diagnóstico , Adulto , Estudios Retrospectivos , Curva ROC , Biomarcadores/líquido cefalorraquídeo , Líquido Cefalorraquídeo/diagnóstico por imagen , AncianoRESUMEN
Neuromyelitis optica spectrum disorder (NMOSD), also known as Devic disease, is an autoimmune central nervous system disorder in humans that commonly causes inflammatory demyelination in the optic nerves and spinal cord. Inflammation in the optic nerves is termed optic neuritis (ON). ON is a common clinical presentation; however, it is not necessarily present in all NMOSD patients. ON in NMOSD can be relapsing and result in severe vision loss. To the best of our knowledge, no study utilises deep learning to classify ON changes on MRI among patients with NMOSD. Therefore, this study aims to deploy eight state-of-the-art CNN models (Inception-v3, Inception-ResNet-v2, ResNet-101, Xception, ShuffleNet, DenseNet-201, MobileNet-v2, and EfficientNet-B0) with transfer learning to classify NMOSD patients with and without chronic ON using optic nerve magnetic resonance imaging. This study also investigated the effects of data augmentation before and after dataset splitting on cropped and whole images. Both quantitative and qualitative assessments (with Grad-Cam) were used to evaluate the performances of the CNN models. The Inception-v3 was identified as the best CNN model for classifying ON among NMOSD patients, with accuracy of 99.5%, sensitivity of 98.9%, specificity of 93.0%, precision of 100%, NPV of 99.0%, and F1-score of 99.4%. This study also demonstrated that the application of augmentation after dataset splitting could avoid information leaking into the testing datasets, hence producing more realistic and reliable results.
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Aprendizaje Profundo , Imagen por Resonancia Magnética , Redes Neurales de la Computación , Neuromielitis Óptica , Nervio Óptico , Neuritis Óptica , Humanos , Neuromielitis Óptica/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Neuritis Óptica/diagnóstico por imagen , Nervio Óptico/diagnóstico por imagen , Nervio Óptico/patología , Femenino , Adulto , Masculino , Persona de Mediana Edad , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
OBJECTIVES: Optic neuritis is a common clinical presentation in patients suffering from multiple sclerosis (MS). Even though optic neuritis is not part of the MS diagnostic criteria, the diagnosis and consideration of differential diagnoses are important in clinical routine. For the evaluation of the optic nerves with MRI, T2-weighted images with fat suppression, known as short tau inversion recovery sequences (STIR), are often used. Besides that, double inversion recovery (DIR) sequences are being used increasingly in MS patients, especially to determine cortical lesions. The Aim of this study was to evaluate the 3D-DIR for the detection of lesions in the optic nerves in MS patients. METHODS: MR examinations of 45 MS-patients containing both STIR and DIR images were independently assessed by two neuroradiologic experienced radiologists, blinded to clinical data. A third neuroradiologic, an experienced radiologist, evaluated the images together, also considering clinical data. These results were considered ground truth and statistically compared to the results of the single readings. To objectify our findings, ROI measurements of affected and unaffected optic nerve segments were made, and a contrast ratio (CR) was calculated. RESULT: DIR images are statistically equivalent to STIR images concerning the detection of lesions in the optic nerve (p < 0.001). The sensitivity of DIR images (84.7 %) and STIR images (77 %), as well as the specificity (92.2 % and 91.2 %), are comparable. The interrater reliability was substantial for both sequences (κ = 0,73) as well as separated for the STIR images (κ = 0.744) and the DIR images (κ = 0.707). The objective analysis revealed significantly higher CRs in DIR images (p < 0.001). CONCLUSION: 3D DIR images showed similar sensitivity and specificity for detecting optic nerve lesions in comparison to dedicated 2D images of the optic nerve. When 3D DIR images are part of the routine scan protocol for evaluating MS patients, additional 2D imaging of the optic nerve is no longer necessary.
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Imagenología Tridimensional , Imagen por Resonancia Magnética , Esclerosis Múltiple , Nervio Óptico , Neuritis Óptica , Humanos , Imagen por Resonancia Magnética/métodos , Femenino , Adulto , Masculino , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/complicaciones , Persona de Mediana Edad , Neuritis Óptica/diagnóstico por imagen , Nervio Óptico/diagnóstico por imagen , Nervio Óptico/patología , Adulto Joven , Sensibilidad y EspecificidadRESUMEN
Bilateral edematous optic disc swelling from papilledema is caused by elevated intracranial pressure (ICP). Idiopathic intracranial hypertension (IIH), a clinical syndrome with elevated ICP of unclear etiology, is a frequent cause of this condition. IIH typically affects obese middle-aged females. Papilledema usually has a fairly symmetrical bilateral pattern. Unilateral papilledema is a rare disorder that must be detected early to avoid optic nerve damage. However, the etiology of unilateral papilledema remains unclear. Based on bilateral optic nerve sheath diameter measurements, we aimed to find an explanation for the unilaterality in this rare case.
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Nervio Óptico , Papiledema , Humanos , Papiledema/diagnóstico , Papiledema/etiología , Femenino , Nervio Óptico/patología , Nervio Óptico/diagnóstico por imagen , Disco Óptico , Adulto , Presión Intracraneal , Agudeza Visual , Tomografía de Coherencia Óptica/métodos , Seudotumor Cerebral/diagnóstico , Seudotumor Cerebral/complicaciones , Imagen por Resonancia MagnéticaRESUMEN
Armadillo repeat-containing X-linked protein-1 (Armcx1) is a poorly characterized transmembrane protein that regulates mitochondrial transport in neurons. Its overexpression has been shown to induce neurite outgrowth in embryonic neurons and to promote retinal ganglion cell (RGC) survival and axonal regrowth in a mouse optic nerve crush model. In order to evaluate the functions of endogenous Armcx1 in vivo, we have created a conditional Armcx1 knockout mouse line in which the entire coding region of the Armcx1 gene is flanked by loxP sites. This Armcx1fl line was crossed with mouse strains in which Cre recombinase expression is driven by the promoters for ß-actin and Six3, in order to achieve deletion of Armcx1 globally and in retinal neurons, respectively. Having confirmed deletion of the gene, we proceeded to characterize the abundance and morphology of RGCs in Armcx1 knockout mice aged to 15 months. Under normal physiological conditions, no evidence of aberrant retinal or optic nerve development or RGC degeneration was observed in these mice. The Armcx1fl mouse should be valuable for future studies investigating mitochondrial morphology and transport in the absence of Armcx1 and in determining the susceptibility of Armcx1-deficient neurons to degeneration in the setting of additional heritable or environmental stressors.
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Proteínas del Dominio Armadillo , Células Ganglionares de la Retina , Animales , Ratones , Proteínas del Dominio Armadillo/genética , Proteínas del Dominio Armadillo/metabolismo , Ratones Noqueados , Nervio Óptico/metabolismo , Retina/metabolismo , Células Ganglionares de la Retina/metabolismoRESUMEN
A compromised capacity to maintain NAD pools is recognized as a key underlying pathophysiological feature of neurodegenerative diseases. NAD acts as a substrate in major cell functions including mitochondrial homeostasis, cell signalling, axonal transport, axon/Wallerian degeneration, and neuronal energy supply. Dendritic degeneration is an early marker of neuronal stress and precedes cell loss. However, little is known about dendritic structural preservation in pathologic environments and remodelling in mature neurons. Retinal ganglion cell dendritic atrophy is an early pathological feature in animal models of the disease and has been demonstrated in port-mortem human glaucoma samples. Here we report that a nicotinamide (a precursor to NAD through the NAD salvage pathway) enriched diet provides robust retinal ganglion cell dendritic protection and preserves dendritic structure in a rat model of experimental glaucoma. Metabolomic analysis of optic nerve samples from the same animals demonstrates that nicotinamide provides robust metabolic neuroprotection in glaucoma. Advances in our understanding of retinal ganglion cell metabolic profiles shed light on the energetic shift that triggers early neuronal changes in neurodegenerative diseases. As nicotinamide can improve visual function short term in existing glaucoma patients, we hypothesize that a portion of this visual recovery may be due to dendritic preservation in stressed, but not yet fully degenerated, retinal ganglion cells.
Asunto(s)
Modelos Animales de Enfermedad , Glaucoma , Fármacos Neuroprotectores , Niacinamida , Células Ganglionares de la Retina , Animales , Niacinamida/farmacología , Células Ganglionares de la Retina/efectos de los fármacos , Células Ganglionares de la Retina/patología , Células Ganglionares de la Retina/metabolismo , Glaucoma/metabolismo , Glaucoma/patología , Fármacos Neuroprotectores/farmacología , Ratas , Relación Dosis-Respuesta a Droga , Masculino , Administración Oral , Nervio Óptico/efectos de los fármacos , Nervio Óptico/patología , Nervio Óptico/metabolismo , Neuroprotección/efectos de los fármacos , Neuroprotección/fisiología , Dendritas/efectos de los fármacos , Dendritas/patología , Dendritas/metabolismo , Complejo Vitamínico B/farmacología , Complejo Vitamínico B/administración & dosificaciónRESUMEN
As part of the central nervous system, the optic nerve, composed of axons from retinal ganglion cells (RGCs), generally fails to regenerate on its own when injured in adult mammals. An innovative approach to promoting optic nerve regeneration involves manipulating the interactions between amacrine cells (ACs) and RGCs. Here, we identified a unique AC subtype, dopaminergic ACs (DACs), that responded early after optic nerve crush by down-regulating neuronal activity and reducing retinal dopamine (DA) release. Activating DACs or augmenting DA release with levodopa demonstrated neuroprotective effects and modestly enhanced axon regeneration. Within this context, we pinpointed the DA receptor D1 (DRD1) as a critical mediator of DAC-derived DA and showed that RGC-specific Drd1 overexpression effectively overcame subtype-specific barriers to regeneration. This strategy markedly boosted RGC survival and axon regeneration after crush and preserved vision in a glaucoma model. This study unveils the crucial role of DAC-derived DA signaling in optic nerve regeneration, holding promise for therapeutic insights into neural repair.