ABSTRACT
A high-fidelity synthetic diagnostic has been developed for the ITER core x-ray crystal spectrometer diagnostic based on x-ray ray tracing. This synthetic diagnostic has been used to model expected performance of the diagnostic, to aid in diagnostic design, and to develop engineering tolerances. The synthetic model is based on x-ray ray tracing using the recently developed xicsrt ray tracing code and includes a fully three-dimensional representation of the diagnostic based on the computer aided design. The modeled components are: plasma geometry and emission profiles, highly oriented pyrolytic graphite pre-reflectors, spherically bent crystals, and pixelated x-ray detectors. Plasma emission profiles have been calculated for Xe44+, Xe47+, and Xe51+, based on an ITER operational scenario available through the Integrated Modelling & Analysis Suite database, and modeled within the ray tracing code as a volumetric x-ray source; the shape of the plasma source is determined by equilibrium geometry and an appropriate wavelength distribution to match the expected ion temperature profile. All individual components of the x-ray optical system have been modeled with high-fidelity producing a synthetic detector image that is expected to closely match what will be seen in the final as-built system. Particular care is taken to maintain preservation of photon statistics throughout the ray tracing allowing for quantitative estimates of diagnostic performance.
ABSTRACT
Neutral [X-{Ir2 }-{Ir2 }-X] (X=Cl, Br, SCN, I) and dicationic [L-{Ir2 }-{Ir2 }-L]2+ (L=MeCN, Me2 CO) tetrametallic iridium chains made by connecting two dinuclear {Ir2 } units ({Ir2 }=[Ir2 (µ-OPy)2 (CO)4 ], OPy=2-pyridonate) by an iridium-iridium bond are described. The complexes exhibit fractional averaged oxidation states of +1.5 and electronic delocalization along the metallic chain. While the axial ligands do not significantly affect the metal-metal bond lengths, the metallic chain has a significant impact on the iridium-L/X bond distances. The complexes show free rotation around the unsupported iridium-iridium bond in solution, with a low-energy transition state for the chloride chain. The absorption spectra of these complexes show characteristic bands at 438-504â nm, which can be fine-tuned by varying the terminal capping ligands.
ABSTRACT
Piperazine rings are essential motifs frequently found in commercial drugs. However, synthetic methodologies are mainly limited to N-substituted piperazines, preventing structural diversity. Disclosed herein is a straightforward catalytic method for the synthesis of complex C-substituted piperazines based on an uncommon head-to-head coupling of easily prepared imines. This 100% atom-economic process allows the selective formation of a sole diastereoisomer, a broad substrate scope, and a good functional group tolerance employing a bench-stable iridium catalyst under mild reaction conditions. Key to the success is the addition of N-oxides to the reaction mixture, as they notably enhance the catalytic activity and selectivity.
ABSTRACT
Alzheimer's disease (AD) is the most common cause of dementia among older adults. APOE3 Christchurch (R136S, APOE3Ch ) variant homozygosity was reported in an individual with extreme resistance to autosomal dominant AD due to the PSEN1 E280A mutation. This subject had a delayed clinical age at onset and resistance to tauopathy and neurodegeneration despite extremely high amyloid plaque burden. We established induced pluripotent stem (iPS) cell-derived cerebral organoids from this resistant case and from a non-protected kindred control (with PSEN1 E280A and APOE3/3 ). We used CRISPR/Cas9 gene editing to successfully remove the APOE3Ch to wild type in iPS cells from the protected case and to introduce the APOE3Ch as homozygote in iPS cells from the non-protected case to examine causality. We found significant reduction of tau phosphorylation (pTau 202/205 and pTau396) in cerebral organoids with the APOE3Ch variant, consistent with the strikingly reduced tau pathology found in the resistant case. We identified Cadherin and Wnt pathways as signaling mechanisms regulated by the APOE3Ch variant through single cell RNA sequencing in cerebral organoids. We also identified elevated ß-catenin protein, a regulator of tau phosphorylation, as a candidate mediator of APOE3Ch resistance to tauopathy. Our findings show that APOE3Ch is necessary and sufficient to confer resistance to tauopathy in an experimental ex-vivo model establishing a foundation for the development of novel, protected case-inspired therapeutics for tauopathies, including Alzheimer's.
ABSTRACT
Summary: Background. Kikuchi-Fujimoto Disease (KFD) or histiocytic necrotizing lymphadenitys is a rare disorder characterized by subacute necrotizing regional lymphadenopathy. It is usually presented as painful cervical nodes and associated with fever, headache, night sweats, nausea, vomiting and sore throat. Etiology of KFD is still unclear, two theories have been proposed: infections and autoimmune origin. Due to recent reports of KFD related to COVID-19 vaccination, the novelty of the mechanism of these vaccines and the immunomodulated role of both matters, a literature and adverse event databases review was carried out in order to shed light on the relationship between these two matters. Methods. A search in the Spanish and the European adverse events databases (FEDRA and Eudravigilance) was performed. Search criteria were any drug and the diagnosis "Histiocytic necrotizing lymphadenitis" according to the Medical Dictionary for Medical Activities version 25.0. All adverse events registered as June 2, 2022, were included. Results. FEDRA encompassed two KFD reports, one related to a mRNA COVID-19 vaccine. Eudravigilance included a total of 62 KFD cases, 14 of them associated to COVID-19 vaccines and eight to other vaccines. Conclusions. Pharmacovigilance is of utter importance in detecting adverse events caused by new vaccines. More research is needed to establish a final connection between KFD and COVD-19 vaccines, but due to the physiopathology of the condition, how vaccines stimulate the immune system and the high number of reported KFD cases with vaccines given its rare incidence, it is plausible to think that both entities are related.
Subject(s)
COVID-19 Vaccines , COVID-19 , Histiocytic Necrotizing Lymphadenitis , Humans , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Histiocytic Necrotizing Lymphadenitis/etiology , Histiocytic Necrotizing Lymphadenitis/complications , Pharmacovigilance , Vaccination/adverse effectsABSTRACT
Resumen Introducción: el estudio analizó (a) las diferencias entre madres y padres en sus actividades matemáticas en el hogar y en otros factores del ambiente matemático (actitudes, ansiedad, creencias y expectativas matemáticas) y (b) la asociación entre los factores del ambiente matemático y las actividades matemáticas en el hogar. Método: participaron 266 familias de niños y niñas chilenos de primer a tercer grado de primaria (edad promedio = 93.35 meses, DE = 11.45 meses). Ambos padres contestaron un cuestionario sobre matemáticas en el hogar. Resultados: las madres reportaron realizar actividades matemáticas con mayor frecuencia que los padres. Análisis de ecuaciones estructurales mostraron que las actividades matemáticas realizadas por los padres se relacionaron con sus creencias, actitudes y expectativas matemáticas; mientras que las de las madres se relacionaron con sus creencias, actitudes y género de los niños. Conclusiones: los hallazgos aportan a la comprensión del ambiente matemático en el hogar.
Abstract Introduction: The study analyzes (a) the differences between mothers and fathers in their home math activities and home math environment factors (math attitudes, anxiety, beliefs, and expectations) and (b) the associations among the home math environment factors and home math activities of Chilean families. Method: Participants were 266 families of boys and girls attending grades 1-3 (mean age = 93.35 months, DS = 11.45 months). Both parents of each child independently answered a home math questionnaire. Results: Mothers reported doing more math activities with their children than fathers. The structural equation model analyses showed that the frequency with which fathers engage in home math activities was related to their math beliefs, attitudes, and expectations, whereas maternal home math activities were related to their beliefs, attitudes, and the gender of the child. Conclusions: The findings contribute to the understanding of the home math environment.
ABSTRACT
Monochromators for synchrotron radiation beamlines typically use perfect crystals for the hard X-ray regime and gratings for soft X-rays. There is an intermediate range, typically 1-3â keV (tender X-rays), which common perfect crystals have difficulties covering and gratings have low efficiency, although some less common crystals with high d-spacing could be suitable. To evaluate the suitability of these crystals for a particular beamline, it is useful to evaluate the crystals' performance using tools such as ray-tracing. However, simulations for double-crystal monochromators are only available for the most used crystals such as Si, Ge or diamond. Here, an upgrade of the SHADOW ray-tracing code and complementary tools in the OASYS suite are presented to simulate high d-spacing crystals with arbitrary, and sometimes complex, structures such as beryl, YB66, muscovite, etc. Isotropic and anisotropic temperature factors are also considered. The YB66 crystal with 1936 atomic sites in the unit cell is simulated, and its applicability for tender X-ray monochromators is discussed in the context of new low-emittance storage rings.
ABSTRACT
Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic extracellular matrix disease caused by deficiency in type VII collagen (Col VII). The disease manifests with devastating mucocutaneous fragility leading to progressive fibrosis and metastatic squamous cell carcinomas. Although Col VII abundance is considered the main predictor of symptom course, previous studies have revealed the existence of mutation-independent mechanisms that control disease progression. Here, to investigate and validate new molecular modifiers of wound healing and fibrosis in a natural human setting, and toward development of disease-modulating treatment of RDEB, we performed gene expression profiling of primary fibroblast from RDEB siblings with marked phenotypic variations, despite having equal COL7A1 genotype. Gene enrichment analysis suggested that severe RDEB was associated with enhanced response to TGF-ß stimulus, oxidoreductase activity, and cell contraction. Consistently, we found an increased response to TGF-ß, higher levels of basal and induced reactive oxygen species (ROS), and greater contractile ability in collagen lattices in RDEB fibroblasts (RDEBFs) from donors with severe RDEB vs mild RDEB. Treatment with antioxidants allowed a reduction of the pro-fibrotic and contractile phenotype. Importantly, our analyses revealed higher expression and deposition in skin of the relatively uncharacterized small leucine-rich extracellular proteoglycan PRELP/prolargin associated with milder RDEB manifestations. Mechanistic investigations showed that PRELP effectively attenuated fibroblasts' response to TGF-ß1 stimulus and cell contractile capacity. Moreover, PRELP overexpression in RDEBFs enhanced RDEB keratinocyte attachment to fibroblast-derived extracellular matrix in the absence of Col VII. Our results highlight the clinical relevance of pro-oxidant status and hyper-responsiveness to TGF-ß in RDEB severity and progression. Of note, our study also reveals PRELP as a novel and natural TGF-ß antagonist with a likely dermo-epidermal pro-adhesive capacity.
Subject(s)
Epidermolysis Bullosa Dystrophica , Collagen Type VII/genetics , Epidermolysis Bullosa Dystrophica/genetics , Extracellular Matrix Proteins/genetics , Fibroblasts/metabolism , Fibrosis , Glycoproteins , Humans , Mutation , Small Leucine-Rich Proteoglycans/genetics , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/metabolismABSTRACT
Neuroleptic malignant syndrome is a rare medical emergency associated with the use of antipsychotics and other antidopaminergic drugs. There is no specific test, and diagnosis is based on high clinical suspicion and good differential diagnosis. A clinical picture consistent with hyperthermia, muscle rigidity, altered level of consciousness, together with signs of rhabdomyolysis in analytical studies and a history of taking neuroleptic drugs are the key elements in the detection of this entity. Due to its low incidence and potential mortality, it is essential to publish case reports of neuroleptic malignant syndrome in order to raise awareness of this entity and facilitate diagnostic suspicion when encountering a patient with compatible symptoms. The following is the case of a 79 year old patient with chronic alcohol consumption as the only history of interest, who was given a single dose of haloperidol after an episode of delirium in the postoperative period of conventional trauma surgery. She subsequently developed a picture of progressive deterioration of the level of consciousness, diaphoresis, generalized muscle rigidity, hyperthermia, together with severe metabolic acidosis, hyperlacticaemia, rhabdomyolysis, hypertransaminasemia and hypocalcemia. After ruling out other entities compatible with the clinical picture, neuroleptic malignant syndrome was given as the main diagnostic hypothesis. Diagnosis was confirmed after clinical and analytical improvement following treatment with dantrolene. The patient was discharged from hospital with no sequelae a few days after onset of the condition.
Subject(s)
Antipsychotic Agents , Neuroleptic Malignant Syndrome , Rhabdomyolysis , Aged , Antipsychotic Agents/adverse effects , Female , Fever , Humans , Muscle Rigidity/complications , Muscle Rigidity/drug therapy , Neuroleptic Malignant Syndrome/complications , Neuroleptic Malignant Syndrome/etiology , Postoperative Period , Rhabdomyolysis/chemically induced , Rhabdomyolysis/complicationsABSTRACT
INTRODUCTION: It has been observed in recent years that levels of such molecules as calcitonin gene-related peptide (CGRP) and, to a lesser extent, the pituitary adenylate cyclase-activating peptide are elevated during migraine attacks and in chronic migraine, both in the cerebrospinal fluid and in the serum. Pharmacological reduction of these proteins is clinically significant, with an improvement in patients' migraines. It therefore seems logical that one of the main lines of migraine research should be based on the role of CGRP in the pathophysiology of this entity. DEVELOPMENT: The Spanish Society of Neurology's Headache Study Group decided to draft this document in order to address the evidence on such important issues as the role of CGRP in the pathophysiology of migraine and the mechanism of action of monoclonal antibodies and gepants; and to critically analyse the results of different studies and the profile of patients eligible for treatment with monoclonal antibodies, and the impact in terms of pharmacoeconomics. CONCLUSIONS: The clinical development of gepants, which are CGRP antagonists, for the acute treatment of migraine attacks, and CGRP ligand and receptor monoclonal antibodies offer promising results for these patients.
Subject(s)
Calcitonin Gene-Related Peptide , Migraine Disorders , Antibodies, Monoclonal/therapeutic use , Calcitonin Gene-Related Peptide/metabolism , Calcitonin Gene-Related Peptide Receptor Antagonists/therapeutic use , Headache/drug therapy , Humans , Migraine Disorders/drug therapyABSTRACT
Although many more eyes of children with retinoblastoma are salvaged now compared to just 10 years ago, the control of vitreous seeding remains a challenge. The introduction of intravitreal injection of melphalan has enabled more eyes to be salvaged safely but with definite retinal toxicity. Intensive treatment with high-dose intravitreal topotecan may be a strategy to control tumor burden because of its cell cycle-dependent cytotoxicity and the proven safety in humans. Therefore, we evaluated the ocular and systemic safety of repeated high-dose intravitreal injections of topotecan in rabbits. Systemic and ocular toxicity was assessed in non-tumor-bearing rabbits after four weekly injections of three doses of topotecan (10 µg, 25 µg, and 50 µg) or vehicle alone. Animals were evaluated weekly for general and ophthalmic clinical status. One week after the last injection, vitreous and plasma samples were collected for drug quantification and the enucleated eyes were subjected to histological assessment. Weight, hair loss, or changes in hematologic values were absent during the study period across all animal groups. Eyes injected with all topotecan doses or vehicle showed no signs of anterior segment inflammation, clinical or histologic evidence of damage to the retina, and ERG parameters remained unaltered throughout the study. Vitreous and plasma topotecan lactone concentrations were undetectable. Four weekly intravitreal injections of topotecan up to 50 µg in the animal model or a 100 µg human equivalent dose were not toxic for the rabbit eye. High doses of topotecan may show promising translation to the clinic for the management of difficult-to-treat retinoblastoma vitreous seeds.
Subject(s)
Retinal Neoplasms , Retinoblastoma , Animals , Intravitreal Injections , Rabbits , Retinal Neoplasms/drug therapy , Retinal Neoplasms/pathology , Retinoblastoma/drug therapy , Retinoblastoma/pathology , Topotecan/toxicity , Vitreous Body/pathologyABSTRACT
OBJECTIVES: This document presents the fundamentals of speech audiometry in noise, general requirements for implementation and criteria for choice among the tests available in French according to the health-professional's needs. MATERIAL AND METHODS: The recommendations are based on a systematic analysis of the literature carried out by a multidisciplinary group of doctors, audiologists and audioprosthetists from all over France. They are graded A, B, C or expert opinion according to decreasing level of scientific evidence. RESULTS: Eight tests of speech audiometry in noise can be used in France. CONCLUSION: To be complete, evaluation of hearing status requires testing understanding of speech in noise. The examination must begin with a minimum of two measurements familiarizing the subject with the test procedure. For initial diagnosis, adaptive procedures establishing the 50% speech reception threshold (SRT50) in noise are to be preferred in order to obtain a rapid and standardized measurement of perception of speech in noise. When the aim is to measure real-life speech comprehension, tests based on sentences, cocktail-party noise and free-field stimulation are to be preferred. Prosthetic gain is evaluated exclusively in free field. This is the only way to evaluate the contribution of binaurality and to measure perception in noise in an environment as close as possible to real life. In order to avoid acoustic interference in free field, at least five loudspeakers should be used, in particular for evaluating the effectiveness of directional microphones, CROS devices enabling sounds picked up in the damaged ear to be rerouted to the functional ear, or bimodal fitting (i.e., when hearing is enabled by two modalities: for example, hearing aid for one ear, cochlear implant for the other).
Subject(s)
Audiology , Cochlear Implants , Hearing Aids , Otolaryngology , Speech Perception , Adult , Humans , SpeechABSTRACT
Neuroleptic malignant syndrome is a rare medical emergency associated with the use of antipsychotics and other antidopaminergic drugs. There is no specific test, and diagnosis is based on high clinical suspicion and good differential diagnosis. A clinical picture consistent with hyperthermia, muscle rigidity, altered level of consciousness, together with signs of rhabdomyolysis in analytical studies and a history of taking neuroleptic drugs are the key elements in the detection of this entity. Due to its low incidence and potential mortality, it is essential to publish case reports of neuroleptic malignant syndrome in order to raise awareness of this entity and facilitate diagnostic suspicion when encountering a patient with compatible symptoms. The following is the case of a 79 year old patient with chronic alcohol consumption as the only history of interest, who was given a single dose of haloperidol after an episode of delirium in the postoperative period of conventional trauma surgery. She subsequently developed a picture of progressive deterioration of the level of consciousness, diaphoresis, generalized muscle rigidity, hyperthermia, together with severe metabolic acidosis, hyperlacticaemia, rhabdomyolysis, hypertransaminasemia and hypocalcemia. After ruling out other entities compatible with the clinical picture, neuroleptic malignant syndrome was given as the main diagnostic hypothesis. Diagnosis was confirmed after clinical and analytical improvement following treatment with dantrolene. The patient was discharged from hospital with no sequelae a few days after onset of the condition.
ABSTRACT
INTRODUCTION: After the European Headache Federation (EHF) Congress, renowned Spanish neurologists specialised in migraine presented the most significant latest developments in research in this field at the Post-EHF Meeting. DEVELOPMENT: The main data presented concerning the treatment of chronic and episodic migraine were addressed, with attention paid more specifically to those related to preventive treatments and real-life experience in the management of the disease. An important review was carried out of the new therapeutic targets and the possibilities they offer in terms of understanding the pathophysiology of migraine and its treatment. An update was also presented of the latest developments in the treatment of migraine with fremanezumab, a monoclonal antibody recently authorised by the European Medicines Agency. Participants were also given an update on the latest developments in basic research on the pathology, as well as an overview of the symptoms of migraine and COVID-19. Finally, the repercussions of migraine in terms of its burden on the care and economic resources of the health system were addressed, along with its impact on society. CONCLUSIONS: The meeting summarised the content presented at the 14th EHF Congress, which took place in late June/early July 2020.
TITLE: I Reunión Post-European Headache Federation: revisión de las novedades presentadas en el Congreso de la European Headache Federation de 2020.Introducción. Tras la celebración del congreso de la European Headache Federation (EHF), reconocidos neurólogos españoles expertos en el tratamiento de la migraña expusieron en la Reunión Post-EHF las principales novedades presentadas en el congreso y relacionadas con ese ámbito. Desarrollo. Se abordan los principales datos presentados relacionados con el tratamiento de la migraña crónica y episódica; concretamente, los relacionados con los tratamientos preventivos y la experiencia en vida real en el manejo de la enfermedad. Se hizo una importante revisión de las nuevas dianas terapéuticas y las posibilidades que ofrecen en cuanto al conocimiento de la fisiopatología de la migraña y su tratamiento. Asimismo, se hizo una actualización de las novedades presentadas en el tratamiento de la migraña con fremanezumab, anticuerpo monoclonal recientemente autorizado por la Agencia Europea de Medicamentos. Se hizo una actualización de las novedades en investigación básica en la patología, así como una relación de los síntomas de migraña y COVID-19. Finalmente, se abordaron las implicaciones de la migraña en la carga sanitaria asistencial y económica, y su impacto en la sociedad. Conclusiones. En la reunión se hizo un resumen del contenido presentado en el 14 Congreso de la EHF, que tuvo lugar a finales de junio y principios de julio de 2020.
Subject(s)
Migraine Disorders/therapy , Antibodies, Monoclonal/therapeutic use , Congresses as Topic , Europe , Humans , Migraine Disorders/drug therapy , Migraine Disorders/etiology , Practice Guidelines as TopicABSTRACT
Here we report the discovery of ceramic fragments that form part of a Gorgoneion, a ceramic image representation of the Gorgon Medusa. The fragments were found in a deep part of Gorham's Cave, well known to ancient mariners as a natural shrine, between the 8th and 2nd century BCE. We discuss the context of this discovery, both within the inner topography of the cave itself, and also the broader geographical context. The discovery is situated at the extreme western end of the Mediterranean Sea, where it meets the Atlantic Ocean. The location was known to ancient mariners as the northern Pillar of Herakles, which marked the end of the known world. We relate the discovery, and its geographical and chronological context, to Greek legends that situated the lair of the Gorgon sisters at a location which coincides with the physical attributes and geographical position of Gorham's Cave. We thus provide, uniquely, a geographical and archaeological context to the myth of Perseus and the slaying of the Gorgon Medusa.
Subject(s)
Archaeology/methods , Caves , Ceramics/chemistry , HumansABSTRACT
INTRODUCTION: Medication overuse headache is a secondary headache in which the regular or frequent use of analgesics can increase the frequency of the episodes, causing the transition from episodic to chronic headache. The prevalence of medication overuse headache is approximately 1-2%, with higher rates among women aged 30-50 years and with comorbid psychiatric disorders such as depression or anxiety, or other chronic pain disorders. It is important to be familiar with the management of this disease. To this end, the Spanish Society of Neurology's Headache Study Group has prepared a consensus document addressing this disorder. DEVELOPMENT: These guidelines were prepared by a group of neurologists specialising in headache after a systematic literature review and provides consensus recommendations on the proper management and treatment of medication overuse headache. The treatment of medication overuse headache is often complex, and is based on 4 fundamental pillars: education and information about the condition, preventive treatment, discontinuation of the drug being overused, and treatment for withdrawal symptoms. Follow-up of patients at risk of recurrence is important. CONCLUSIONS: We hope that this document will be useful in daily clinical practice and that it will update and improve understanding of medication overuse headache management.
Subject(s)
Headache Disorders, Secondary , Analgesics/adverse effects , Female , Headache/drug therapy , Headache Disorders/drug therapy , Headache Disorders, Secondary/epidemiology , Humans , Substance Withdrawal Syndrome/drug therapyABSTRACT
BACKGROUND: Ischemia-reperfusion injury in free flaps is associated with tissue damage and is one of the main factors causing flap failure in reconstructive microsurgery. The aim of this study is to assess whether any ischemia-reperfusion injury takes place during a microsurgical flap reconstruction as seen through the levels of malondialdehyde (MDA) and superoxide dismutase, biomarkers of oxidative stress, and to analyze the effect of lidocaine in this process. METHODS: Twenty-four patients operated for immediate breast reconstruction using the Deep Inferior Epigastric Perforator free flap technique were divided into two groups: one group was treated with a lidocaine intravenous perfusion and the other group with a saline perfusion. MDA and superoxide dismutase (SOD) levels were measured at several points before, during, and after surgery. RESULTS: There was an increase in MDA levels in both groups, but the lidocaine group experienced a decrease during reperfusion. On the other hand, we observed a rise in SOD levels in both groups, but a decrease during reperfusion in the placebo group. However, these differences between groups were not statistically significant. CONCLUSIONS: The decreased SOD activity and increased MDA content in our research prove a redox imbalance and high reactive oxygen species levels in flaps, indicating that tissues experience ischemia-reperfusion injury during microsurgical reconstruction. Lidocaine may have a protective effect in free flap surgery, but our results were not statistically significant, so further studies will be required.
Subject(s)
Anesthetics, Local/administration & dosage , Epigastric Arteries/transplantation , Lidocaine/administration & dosage , Mammaplasty/methods , Perforator Flap/blood supply , Reperfusion Injury/prevention & control , Adult , Biomarkers/blood , Breast Neoplasms/surgery , Double-Blind Method , Female , Humans , Infusions, Intravenous , Malondialdehyde/blood , Microsurgery , Middle Aged , Oxidative Stress , Prospective Studies , Superoxide Dismutase/bloodABSTRACT
BACKGROUND AND PURPOSE: OnabotulinumtoxinA is an effective preventive treatment for chronic migraine (CM). In CM, in addition to a reduction in headache frequency, a decreased reliance on oral prophylactics is also indicative of treatment effectiveness. This study aimed to quantify the change in the use of oral prophylactics after treatment with onabotulinumtoxinA in patients with CM. METHODS: This was a retrospective, multicentric, cross-sectional study. Patients with CM (International Classification of Headache Disorders-3beta) that had been treated with onabotulinumtoxinA were enrolled consecutively. We collected parameters related to each patient's pre-treatment situation, as well as their current situation, focusing on frequency and intensity of migraine, number of oral prophylactics and the respective cycle of onabotulinumtoxinA. Univariate and logistic regression analyses were performed. RESULTS: We included 542 patients, 90.0% of whom were taking oral preventive treatments. During treatment with onabotulinumtoxinA, 47.8% withdrew at least one prophylactic and 41.6% stopped using oral prophylactics altogether. Factors associated with a reduction or cessation of oral prophylactics were >50% improvement in frequency and intensity, remission to episodic migraine, use of topiramate as an initial treatment, increased number of infiltrations and shorter chronification period (P < 0.05). The multivariate analysis showed that a chronification period <20 months, more than five cycles of onabotulinumtoxinA, >50% improvement in pain intensity and topiramate as an initial treatment were predictors of a reduction in oral prophylactics (area under the curve, 70.3%; P < 0.001). CONCLUSIONS: Our study demonstrated the efficacy and safety of onabotulinumtoxinA. This treatment reduced the use of oral prophylactics. Withdrawal of oral prophylactics was most likely to occur after five cycles of treatment.