Severe disease reactivation in seropositive neuromyelitis optica spectrum disorders patients after stopping eculizumab treatment.

INTRODUCTION: Neuromyelitis optica spectrum disorders (NMOSD) is an autoimmune, inflammatory disease of the central nervous system affecting the optic nerves and spinal cord. Most NMOSD patients have autoantibodies against the astrocyte water channel protein aquaporin-4 (AQP4). Eculizumab treatment is used effectively and safely in AQP4-IgG+ NMOSD. Our study evaluated the prognosis and outcomes of all clinical trial (PREVENT) patients from Turkey who received eculizumab treatment for AQP4-IgG+ NMOSD. METHOD: Clinical and demographic data of all patients enrolled in the PREVENT and OLE clinical trial in Turkey were analyzed during the study period and after the study ended. Clinical follow-up results were recorded in detail in patients who had to discontinue eculizumab treatment. RESULTS: The study included 10 patients who participated in PREVENT and OLE. Seven patients completed the studies, three patients did not continue the study and were switched to other treatments. Only one of the seven patients was able to continue treatment after eculizumab was approved in AQP4-IgG+NMOSD. The other six patients could not continue treatment due to reimbursement conditions. Four of the six patients who could not continue eculizumab treatment experienced early relapse (within the first three months after stopping the drug). All of these patients had high disease activity before eculizumab and had never relapsed under eculizumab treatment over the long term. CONCLUSION: Eculizumab was used effectively and safely in Turkish AQP4-IgG+NMOSD patients with high disease activity. Disease reactivation and relapse may occur after discontinuation of eculizumab treatment in patients with a long-term stable course. In these cases, close monitoring for disease reactivation is recommended.

The Turkish experience of COVID-19 infection in people with NMOSD and MOGAD: A milder course?

BACKGROUND: COVID-19 is a multisystemic infection with variables consequences depending on individual and comorbid conditions. The course and outcomes of COVID-19 during neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) are not clearly known. OBJECTIVE/METHODS: The aim of this study was to examine the features and outcomes of COVID-19 infection in NMOSD and MOGAD patients. The patients' demographic and clinical factors, disease modifying treatment (DMT) used and disease information of COVID-19 infection were recorded. Conditions leading to hospitalization and severe exposure to COVID-19 infection were also analyzed. RESULTS: The study included 63 patients from 25 centers. Thirty-two patients (50.8%) belong to AQP-4 seropositive group, 13 (20.6%) and 18 (28.6%) were in MOG-positive and double-seronegative groups, respectively. Risk factors for severe COVID-19 infection and hospitalization were advanced age, high disability level and the presence of comorbid disease. Disease severity was found to be high in double-seronegative NMOSD and low in MOGAD patients. No statistically significant effect of DMTs on disease severity and hospitalization was found. CONCLUSION: In NMOSD and MOGAD patients, advanced age, high disability and presence of comorbid disease pose risks for severe COVID-19 infection. There was no direct significant effect of DMTs for COVID-19 infection.

Evaulating peripapillary vessel density in regressed papilledema in idiopathic intracranial hypertension patients.

PURPOSE: To evaluate the retinal nerve fiber layer (RNFL) thickness, the ganglion cell complex (GCC) and vessel density of the radial peripapillary capillary (RPC) plexus of eyes with regressed papilledema in idiopathic intracranial hypertension (IIH) patients using optical coherence tomography angiography (OCT-A) and comparing the results with healthy controls. MATERIALS AND METHODS: Fifty-one eyes of 31 patients diagnosed with IIH and 52 eyes of 52 healthy subjects were enrolled in this study. All patients underwent a complete ophthalmological examination and a 4.5 × 4.5 mm peripapillary OCT-A scanning. The quantitative results of the peripapillary RNFL and GCC thicknesses and vessel density of the RPC were analyzed. RESULTS: The vessel density in the inferior, superior nasal, and inferior nasal sectors of the patients with IIH significantly exceeded the vessel density of the healthy controls (P = 0.008, P = 0.008, and P = 0.000, respectively). The RNFL and GCC thickness measurements were comparable in both groups. CONCLUSIONS: Patients with IIH show vascular abnormalities in the inferior nasal region, which can be detected with OCT-A. As a noninvasive imaging modality, OCT-A could provide a new perspective for understanding the pathophysiology of IIH and could also be useful in the follow-up of these patients.

Design of ß-Titanium microstructures for implant materials.

The present work addresses the design of ß-Titanium alloy, TNTZ, microstructure to be used in biomedical applications as implant materials. The TNTZ alloy has recently started to attract interest in the area of biomedical engineering as it can provide elastic modulus values that are comparable to the modulus of the human bone. Such a match between the implant and bone significantly increases the compatibility and functionality of the implant material with the human body. Experimental studies reveal that the modulus of TNTZ varies around 55-60 GPa, whereas the bones typically have modulus around 25-30 GPa. Therefore, to achieve a better match in modulus values and further improve the compatibility of the implant, we present a computational design study. As the properties of materials are significantly affected by the underlying microstructure, we focus on identifying the optimum microstructures. Our goal is to minimize the difference between the elastic modulus values of the microstructure and the bone. To ensure the manufacturability of such an optimum design solution, we analyze the microstructural evolution during deformation processing to obtain the optimum microstructure that can be processed. The outcomes of our analysis demonstrated that the elastic modulus of TNTZ can be as low as 48 GPa.

Uncertainty Quantification for Ti-7Al Alloy Microstructure with an Inverse Analytical Model (AUQLin).

The present study addresses an inverse problem for observing the microstructural stochasticity given the variations in the macro-scale material properties by developing an analytical uncertainty quantification (UQ) model called AUQLin. The uncertainty in the material property is modeled with the analytical algorithm, and then the uncertainty propagation to the microstructure is solved with an inverse problem that utilizes the transformation of random variables principle. The inverse problem leads to an underdetermined linear system, and thus produces multiple solutions to the statistical features of the microstructure. The final solution is decided by solving an optimization problem which aims to minimize the difference between the computed and experimental statistical parameters of the microstructure. The final result for the computed microstructural uncertainty is found to provide a good match to the experimental microstructure information.

Multi-scale computational modeling of lightweight aluminum-lithium alloys.

The present study addresses the multi-scale computational modeling of a lightweight Aluminum-Lithium (Al-Li) 2070 alloy. The Al-Li alloys display significant anisotropy in material properties because of their strong crystallographic texture. To understand the relationships between processing, microstructural textures at different material points and tailored material properties, a multi-scale simulation is performed by controlling the texture evolution during deformation. To achieve the multi-scale framework, a crystal plasticity model based on a one-point probability descriptor, Orientation Distribution Function (ODF), is implemented to study the texture evolution. Next, a two-way coupled multi-scale model is developed, where the deformation gradient at the macro-scale integration points is passed to the micro-scale ODF model and the homogenized stress tensor at the micro-scale is passed back to the macro-scale model. A gradient-based optimization scheme which incorporates the multi-scale continuum sensitivity method is utilized to calibrate the slip system parameters of the alloy using the available experimental data. Next, the multi-scale simulations are performed for compression and tension using the calibrated crystal plasticity model, and the texture data is compared to the experiments. With the presented multi-scale modeling scheme, we achieve the location-specific texture predictions for a new generation Al-Li alloy for different deformation processes.

Antiepileptic treatment for anti-NMDA receptor encephalitis: the need for video-EEG monitoring.

Anti-NMDA receptor encephalitis is a severe disorder characterised clinically by seizures, autonomic instability, and severe disturbances of memory, behaviour, and cognition. Due to the severity of symptoms, many patients are admitted to the intensive care unit. For some patients, the presence of various movement disorders and abnormal autonomic signs, as well as a history of seizures, lead to a false impression of status epilepticus, which is reported in 6% of the cases. Here, we present two young female patients, one of whom had ovarian teratoma. Both patients were referred to our neurological intensive care unit with a diagnosis of status epilepticus. However, prolonged video-EEG findings were compatible with encephalopathy. We avoided aggressive treatment with intravenous anaesthetics and both patients recovered after immunotherapy, one of whom received surgery. Physicians should be cautious in interpreting abnormal movements and autonomic signs in such patients and video-EEG monitoring is advised when status epilepticus is suspected. [Published with video sequences].

[Assessment of the effect of intrathecal levobupivacaine combined with fentanyl or morphine on postoperative analgesia in patients undergoing cesarean section]. / Sezaryenlerde intratekal levobupivakaine ilave edilen fentanil ve morfinin postoperatif agri üzerine etkisinin degerlendirilmesi.

OBJECTIVES: Our prospective, randomized, double-blind study aimed to detect the effect of intrathecal levobupivacaine combined with fentanyl or morphine on the postoperative analgesia in patients undergoing cesarean section. METHODS: After approval by the hospital ethics committee and obtaining written informed consent, ASA I-II parturients undergoing elective cesarean section were enrolled in this study. None of the patients had any contraindication for spinal anesthesia or sensitivity to local anesthetics. Patients were randomly assigned in a double-blinded fashion to receive either intrathecal 10 mg 5% levobupivacaine + 0.1 mg morphine (Group M, n=30) or 10 mg 5% levobupivacaine + 20 mcg fentanyl (Group F, n=30). The onset of sensorial block and anesthesia, interval of effective analgesia until the first analgesic requirement, disappearance of motor block according to modified Bromage scale, duration of spinal analgesia, additional analgesic requirement, amount of additional analgesic, adverse effects, and postoperative patient satisfaction were recorded. RESULTS: The additional analgesic requirement period was significantly longer in Group M than Group F (p<0.001). Intraoperative and postoperative complications were significantly higher in Group F than Group M (p<0.05). Intended, delivered and total analgesic amount values were significantly higher in Group F than Group M (p<0.001). Patient satisfaction and presentation elsewhere were significantly higher in Group M than Group F (p<0.01). CONCLUSION: Despite more adverse effects, additional analgesic requirement is lower in Group M, and the long-term painless postoperative period accounts for the choice by mothers.