Hematologic Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference.

CONTEXT: Studies of organ dysfunction in children are limited by a lack of consensus around organ dysfunction criteria. OBJECTIVES: To derive evidence-informed, consensus-based criteria for hematologic dysfunction in critically ill children. DATA SOURCES: Data sources included PubMed and Embase from January 1992 to January 2020. STUDY SELECTION: Studies were included if they evaluated assessment/scoring tools to screen for hematologic dysfunction and assessed outcomes of mortality, functional status, organ-specific outcomes, or other patient-centered outcomes. Studies of adults or premature infants, animal studies, reviews/commentaries, small case series, and non-English language studies with inability to determine eligibility were excluded. DATA EXTRACTION: Data were abstracted from each eligible study into a standard data extraction form along with risk of bias assessment. RESULTS: Twenty-nine studies were included. The systematic review supports the following criteria for hematologic dysfunction: thrombocytopenia (platelet count <100000 cells/µL in patients without hematologic or oncologic diagnosis, platelet count <30000 cells/µL in patients with hematologic or oncologic diagnoses, or platelet count decreased ≥50% from baseline; or leukocyte count <3000 cells/µL; or hemoglobin concentration between 5 and 7 g/dL (nonsevere) or <5 g/dL (severe). LIMITATIONS: Most studies evaluated pre-specified thresholds of cytopenias. No studies addressed associations between the etiology or progression of cytopenias overtime with outcomes, and no studies evaluated cellular function. CONCLUSIONS: Hematologic dysfunction, as defined by cytopenia, is a risk factor for poor outcome in critically ill children, although specific threshold values associated with increased mortality are poorly defined by the current literature.

Immunology 101: fundamental immunology for the practicing hematologist.

From an evolutionary perspective, the immune system developed primarily to protect the host from pathogens. In the continuous balance between killing pathogens and protecting host tissues, selective pressures have shaped the discriminatory functions of the immune system. In addition to protection against microbial pathogens, the immune system also plays a critical role in antitumor immunity. Immune dysfunction, either under- or overactivity, is found in a wide range of hematologic disorders. Here we review the fundamental features of the immune system and the key concepts critical to understanding the impact of immune dysfunction on hematologic disorders.

ASSESSMENT OF QUALITATIVE CHANGES IN PERIPHERAL BLOOD CELLS IN CHILDREN - RESIDENTS OF RADIOLOGICALLY CONTAMINATED TERRITORIES IN THE LATE PERIOD AFTER THE ChNPP ACCIDENT. / OTsINKA IaKISNYKh ZMIN V ELEMENTAKh PERYFERYChNOÏ KROVI U DITEI ­ MEShKANTsIV RADIOAKTYVNO ZABRUDNENYKh TERYTORII U VIDDALENYI PERIOD PISLIa AVARIÏ NA ChAES.

OBJECTIVE: to establish the relationship between quantitative and qualitative parameters of peripheral blood cells(lymphocytes, neutrophilic granulocytes, monocytes, platelets) depending on the type of somatic diseases andannual internal radiation doses from 137Cs in children - residents of radiologically contaminated territories in thelate period after the Chornobyl Nuclear Power Plant (ChNPP) accident. MATERIALS AND METHODS: There were 175 children included in the study comprising residents of radiologically con-taminated territories (n = 79) aged from 4 to 18 years. Annual internal radiation doses in children from 137Cs rangedfrom 0.004 to 0.067 mSv. Certain blood parameters were assessed in a comparative mode in children having got theradiation doses up to 0.01 mSv and higher. The comparison group (n = 96) included children living in settlementsnot attributed to the radiologically contaminated ones. Incidence and type of somatic diseases and its impact onquantitative and qualitative changes in blood parameters (i.e. lymphocyte, neutrophilic granulocyte, monocyte, andplatelet count) were studied. The cell size, state of nucleus, membranes and cytoplasm, signs of proliferative anddegenerative processes were taken into account. RESULTS: Incidence and type of somatic diseases in children did not depend on the annual internal radiation dose.Number of cases of monocytosis was significantly higher among the children exposed to ionizing radiation than inthe comparison group (16.6 % vs. 7.3 %). There were, however, no correlation between these changes and radiationdoses. Number of activated blood monocytes with cytoplasmic basophilia and residues of nucleoli in nuclei washigher in individuals with internal radiation doses > 0.01 mSv. A direct correlation between the qualitative param-eters of monocytes and internal radiation doses was established (rs = 0.60; р < 0.001), as well as a direct correlationof different strength between qualitative parameters of blood cells, indicating their unidirectional pattern depend-ing on the somatic morbid conditions. Regardless of annual internal radiation dose, there was an increase in thenumber of degenerative and aberrant cells vs. the comparison group (р < 0.05), which could be due to the role ofnon-radiation factors. CONCLUSIONS: Results of the assessment of quantitative and qualitative parameters of peripheral blood cells reflect-ed the state of morbid conditions in children and are of a diagnostic value. The identified dose-dependent changesin monocyte lineage of hematopoiesis may be the markers of impact of long-term radionuclide incorporation withfood in children living in environmentally unfavorable conditions after the ChNPP accident.

Efficacy analysis and hemodynamic changes of hematological system diseases after PICC chemotherapy.

OBJECTIVE: The aim of the study was to investigate the efficacy analysis and hemodynamic changes of hematological system diseases after peripherally inserted central catheter (PICC) chemotherapy. PATIENTS AND METHODS: From March 2017 to March 2020, patients with hematological diseases who received chemotherapy in our hospital were selected. The experimental group consisted of 80 patients with PICC, and the control group consisted of 70 patients with routine intravenous injection. The indwelling time, prevalence rate of adverse reactions, hemodynamic indicators before and after chemotherapy and compliance of patients in the two groups were compared. RESULTS: The longest time and average time of indwelling catheter in experimental group were significantly higher than those in control group (p<0.05). The total prevalence rate of adverse reactions in experimental group (3.75%) was significantly lower than that in control group (20%) (p<0.05). The compliance of patients with PICC in experimental group was significantly better than that of patients with superficial intravenous injection in control group. There was no significant difference in hemodynamic indicators between experimental group and control group before and after chemotherapy (p>0.05). There was significant difference in high-shear whole blood indicators, low-shear whole blood viscosity and high-shear whole blood viscosity after chemotherapy (p<0.05), while there was no significant difference in changes of other hemodynamic indicators (p>0.05) or in hemorheological indicators between the two groups after chemotherapy (p>0.05). CONCLUSIONS: The total prevalence of adverse reactions in hematological diseases by PICC infusion is lower than that by superficial vein infusion, and the catheter has no significant influence on hemodynamic indicators in patients. Therefore, PICC catheter is worthy of application and promotion in hematological diseases.

Commonalities Between COVID-19 and Radiation Injury.

As the multi-systemic components of COVID-19 emerge, parallel etiologies can be drawn between SARS-CoV-2 infection and radiation injuries. While some SARS-CoV-2-infected individuals present as asymptomatic, others exhibit mild symptoms that may include fever, cough, chills, and unusual symptoms like loss of taste and smell and reddening in the extremities (e.g., "COVID toes," suggestive of microvessel damage). Still others alarm healthcare providers with extreme and rapid onset of high-risk indicators of mortality that include acute respiratory distress syndrome (ARDS), multi-organ hypercoagulation, hypoxia and cardiovascular damage. Researchers are quickly refocusing their science to address this enigmatic virus that seems to unveil itself in new ways without discrimination. As investigators begin to identify early markers of disease, identification of common threads with other pathologies may provide some clues. Interestingly, years of research in the field of radiation biology documents the complex multiorgan nature of another disease state that occurs after exposure to high doses of radiation: the acute radiation syndrome (ARS). Inflammation is a key common player in COVID-19 and ARS, and drives the multi-system damage that dramatically alters biological homeostasis. Both conditions initiate a cytokine storm, with similar pro-inflammatory molecules increased and other anti-inflammatory molecules decreased. These changes manifest in a variety of ways, with a demonstrably higher health impact in patients having underlying medical conditions. The potentially dramatic human impact of ARS has guided the science that has identified many biomarkers of radiation exposure, established medical management strategies for ARS, and led to the development of medical countermeasures for use in the event of a radiation public health emergency. These efforts can now be leveraged to help elucidate mechanisms of action of COVID-19 injuries. Furthermore, this intersection between COVID-19 and ARS may point to approaches that could accelerate the discovery of treatments for both.

Multisystem effects of COVID-19: a concise review for practitioners.

While COVID-19 has primarily been characterized by the respiratory impact of viral pneumonia, it affects every organ system and carries a high consequent risk of death in critically ill patients. Higher sequential organ failure assessment (SOFA) scores have been associated with increased mortality in patients critically ill patients with COVID-19. It is important that clinicians managing critically ill COVID-19 patients be aware of the multisystem impact of the disease so that care can be focused on the prevention of end-organ injuries to potentially improve clinical outcomes. We review the multisystem complications of COVID-19 and associated treatment strategies to improve the care of critically ill COVID-19 patients.

Deficiency of Adenosine Deaminase 2 in Adults and Children: Experience From India.

OBJECTIVE: Deficiency of adenosine deaminase 2 (DADA2) is a potentially fatal monogenic syndrome characterized by variable manifestations of systemic vasculitis, bone marrow failure, and immunodeficiency. Most cases are diagnosed by pediatric care providers, given the typical early age of disease onset. This study was undertaken to describe the clinical phenotypes and treatment response both in adults and in children with DADA2 in India. METHODS: A retrospective analysis of pediatric and adult patients with DADA2 diagnosed at various rheumatology centers across India was conducted. Clinical characteristics, diagnostic findings, and treatment responses were analyzed in all subjects. RESULTS: In total, 33 cases of DADA2 were confirmed in this cohort between April 2017 and March 2020. Unlike previous studies, nearly one-half of the confirmed cases presented during adulthood. All symptomatic patients exhibited features of vasculitis, whereas constitutional symptoms and anemia were more common in pediatric patients. Cutaneous and neurologic involvement were common, and 18 subjects had experienced at least one stroke. In addition, the clinical spectrum of DADA2 was expanded by recognition of novel features in these patients, including pancreatic infarction, focal myocarditis, and diffuse alveolar hemorrhage. Treatment with tumor necrosis factor inhibitors (TNFi) was initiated in 25 patients. All of the identified disease manifestations showed marked improvement after initiation of TNFi, and disease remission was achieved in 19 patients. Two cases were complicated by tuberculosis infection, and 2 deaths were reported. CONCLUSION: This report presents the first case series of patients with DADA2 from India, diagnosed by adult and pediatric care providers. The findings raise awareness of this syndrome, particularly with regard to its presentation in adults.

Transferrin Receptors in Erythropoiesis.

Erythropoiesis is a highly dynamic process giving rise to red blood cells from hematopoietic stem cells present in the bone marrow. Red blood cells transport oxygen to tissues thanks to the hemoglobin comprised of α- and ß-globin chains and of iron-containing hemes. Erythropoiesis is the most iron-consuming process to support hemoglobin production. Iron delivery is mediated via transferrin internalization by the endocytosis of transferrin receptor type 1 (TFR1), one of the most abundant membrane proteins of erythroblasts. A second transferrin receptor-TFR2-associates with the erythropoietin receptor and has been implicated in the regulation of erythropoiesis. In erythroblasts, both transferrin receptors adopt peculiarities such as an erythroid-specific regulation of TFR1 and a trafficking pathway reliant on TFR2 for iron. This review reports both trafficking and signaling functions of these receptors and reassesses the debated role of TFR2 in erythropoiesis in the light of recent findings. Potential therapeutic uses targeting the transferrin-TFR1 axis or TFR2 in hematological disorders are also discussed.

[William Harvey reinterpreted in the light of species evolution (II) - Physiological and pathological consequences of the evolution of circulation]. / William Harvey réinterprété à la lumière de l'évolution des espèces (II) - Conséquences physiologiques et en pathologie de l'évolution de la circulation.

In the first part of this review [22], "How and why circulatory phylogenesis fits into the evolution of species", we explained that the acquisition of a high-pressure arterial sector, as originally described by William Harvey in 1619, was the consequence, during evolution, of the appearance of vasomotor tone, inducing systemic friction forces (peripheral resistances), which, regulated locally (by vasodilatation), allows to adapt metabolic needs to the demand of functionally active territories. In this second part, we will try to understand how this phylogenesis directly influences the physiology, then the pathologies of the circulatory system in humans which are largely predominant, but not exclusively.

TITLE: William Harvey réinterprété à la lumière de l'évolution des espèces (II) - Conséquences physiologiques et en pathologie de l'évolution de la circulation. ABSTRACT: Dans la première partie de cette revue [20], « comment et pourquoi la phylogenèse circulatoire s'intègre dans l'évolution des espèces ¼, nous avons expliqué que l'acquisition d'un secteur artériel à haute pression, tel qu'initialement décrit par William Harvey en 1619, était la conséquence, au cours de l'évolution, de l'apparition d'un tonus vasomoteur, induisant les forces de friction systémiques (résistances périphériques), qui, régulé localement (par vasodilatation), permet d'adapter les besoins métaboliques à la demande des territoires fonctionnellement actifs. Dans cette seconde partie, nous essaierons de comprendre en quoi cette phylogenèse influence directement la physiologie, puis les pathologies du système circulatoire chez l'homme, qui prédominent largement, mais pas exclusivement, dans le secteur à haute pression.

The erythroblastic island niche: modeling in health, stress, and disease.

Erythropoiesis is one of the most demanding processes in the body, with more than 2 million red blood cells produced every second. Multiple hereditary and acquired red blood cell disorders arise from this complex system, with existing treatments effective in managing some of these conditions but few offering a long-term cure. Finding new treatments relies on the full understanding of the cellular and molecular interactions associated with the production and maturation of red blood cells, which take place within the erythroblastic island niche. The elucidation of processes associated within the erythroblastic island niche in health and during stress erythropoiesis has relied on in vivo modeling in mice, with complexities dissected using simple in vitro systems. Recent progress using state-of-the-art stem cell technology and gene editing has enabled a more detailed study of the human niche. Here, we review these different models and describe how they have been used to identify and characterize the cellular and molecular pathways associated with red blood cell production and maturation. We speculate that these systems could be applied to modeling red blood cell diseases and finding new druggable targets, which would prove especially useful for patients resistant to existing treatments. These models could also aid in research into the manufacture of red blood cells in vitro to replace donor blood transfusions, which is the most common treatment of blood disorders.

Age-Based Comparison of Hematological Toxicity in Patients with Lung Cancer.

INTRODUCTION: Because of the increasing age of the general population, there is an increasing number of older patients with lung cancer. Cancer chemotherapy often causes severe hematological toxicity in older patients. OBJECTIVE: This study aimed to explore the risk factors affecting the hematological toxicity of cytotoxic anticancer drugs in patients with lung cancer. METHODS: Data were retrospectively collected from 194 patients with lung cancer at Niigata University Medical and Dental Hospital, Japan, between April 2011 and March 2016, when the patients underwent their first round of cytotoxic chemotherapy. The patients were divided into three groups on the basis of age: <65, 65-74, and ≥75 years. Physiological functions and laboratory data before treatment, as well as hematological adverse events following chemotherapy, were compared among the groups. RESULTS: Patients aged ≥75 years were significantly more likely to experience grade 3 or 4 neutropenia, compared with patients aged <65 years. However, there were no differences in the incidence of anemia or thrombocytopenia among the age groups. The frequency of febrile neutropenia tended to increase with age. Multivariate analysis showed that age ≥75 years, male sex, and a performance status of ≥2 were independent factors for grade 3 or 4 neutropenia. Patients with 2 or 3 of these factors had a significantly higher frequency of neutropenia, compared with patients who had 0 or 1 of these factors. CONCLUSION: We found that age ≥75 years, male sex, and a performance status of ≥2 were independent risk factors for grade 3 or 4 neutropenia.

Periodic hematological disorders: Quintessential examples of dynamical diseases.

This paper summarizes the evidence supporting the classification of cyclic neutropenia as a dynamical disease and periodic chronic myelogenous leukemia is also considered. The unsatisfactory state of knowledge concerning the genesis of cyclic thrombocytopenia and periodic autoimmune hemolytic anemia is detailed.

Hematologic adverse effects induced by piperacillin-tazobactam: a systematic review of case reports.

Background Piperacillin/tazobactam, a semisynthetic antibiotic, is widely used to treat polymicrobial infections. Its hematologic adverse reactions are rare and the severity can be mild to life-threatening. To our knowledge, there has not been a publication reviewing hematologic abnormalities attributable to piperacillin/tazobactam. Aim of the review To evaluate the characteristic, clinical identification, mechanism and treatment of the hematologic toxicity caused by piperacillin/tazobactam. Method A search of Medline and Embase electronic databases was performed for case reports of adverse reactions of hematologic system related to piperacillin/tazobactam from inception to December 2018. Statistical analysis of demographic, clinical features, laboratory Indexes and treatments was performed using Microsoft EXCEL 2007. Results Fifty-nine references were obtained involving 62 patients. The adverse drug reactions were mainly hemolytic anemia (25, 40.3%), thrombocytopenia (23, 37.1%), and neutropenia (12, 19.4%), which might be accompanied by some typical symptoms. Hemolytic anemia or thrombocytopenia was generally believed to be immune-mediated and often appeared within 10 days, and neutropenia was thought to be related to bone marrow suppression and usually occurred 2 weeks after the initiation of piperacillin/tazobactam. Most patients improved or recovered within a week with treatment or not, and fewer high-quality evidence-based treatments were identified. Conclusion Although part of the patients have clinical symptom, the hematologic adverse drug reactions of piperacillin/tazobactam are easily overlooked or misdiagnosed. Take special caution for patients with prolonged piperacillin/tazobactam treatment or specific disease, and prompt recognition and treatment of the adverse drug reactions are essential and can hasten recovery regardless of the type of side reactions.

Genetic predisposition for increased red blood cell distribution width is an early risk factor for cardiovascular and renal comorbidities.

Red blood cell distribution width (RDW) is a measurement of the variation in size and volume of red blood cells (RBCs). Increased RDW, indicating a high heterogeneity of RBCs, is prominently associated with a variety of illnesses, especially cardiovascular diseases. However, the significance of this association to the onset and progression of cardiovascular and renal diseases is unknown. We hypothesized that a genetic predisposition for increased RDW is an early risk factor for cardiovascular and renal comorbidities. Since there is no known animal model of increased RDW, we examined a CRISPR/Cas9 gene-edited rat model (RfflTD) that presented with features of hematologic abnormalities as well as severe cardiac and renal comorbidities. A mass spectrometry-based quantitative proteomic analysis indicated anemia of these rats, which presented with significant downregulation of hemoglobin and haptoglobin. Decreased hemoglobin and increased RDW were further observed in RfflTD through complete blood count. Next, a systematic temporal assessment detected an early increased RDW in RfflTD, which was prior to the development of other comorbidities. The primary mutation of RfflTD is a 50 bp deletion in a non-coding region, and our study has serendipitously identified this locus as a novel quantitative trait locus (QTL) for RDW. To our knowledge, our study is the first to experimentally pinpoint a QTL for RDW and provides a novel genetic rat model mimicking the clinical association of increased RDW with poor cardio-renal outcome.

In vitro maturation is a viable option for urgent fertility preservation in young women with hematological conditions.

Fertility preservation embraces different techniques developed to improve young women chances of becoming mothers after healing. Among them, in vitro maturation (IVM) procedure is based on oocyte retrieval without any gonadotropin treatment, feasible under locoregional or local anesthesia, with very low operative complications. The present retrospective analysis of a preliminary case series of 25 women diagnosed with Hodgkin or non-Hodgkin lymphoma aims to evaluate the feasibility of IVM for urgent fertility preservation purposes in hematological context. A median of five mature oocytes was cryopreserved after one cycle of IVM, performed without delaying the start of the chemotherapy (median delay from histological diagnosis to start of the chemotherapy 17.5 days). No association was found between lymphomas' characteristics and the number of recovered or frozen oocytes. Although experimental, this technique could be relevant when fertility preservation has to be performed within a short time frame and without additional surgery nor any risk of malignant cells reintroduction.

A Spatiotemporal Analysis of Organ-Specific Lupus Flares in Relation to Atmospheric Variables and Fine Particulate Matter Pollution.

OBJECTIVE: To identify potential clusters of systemic lupus erythematosus (SLE) organ-specific flares and their relationship to fine particulate matter pollution (PM2.5), temperature, ozone concentration, resultant wind, relative humidity, and barometric pressure in the Hopkins Lupus Cohort, using spatiotemporal cluster analysis. METHODS: A total of 1,628 patients who fulfilled the Systemic Lupus International Collaborating Clinics classification criteria for SLE and who had a home address recorded were included in the analysis. Disease activity was assessed using the Lupus Activity Index. Assessment of rash, joint involvement, serositis, and neurologic, pulmonary, renal, and hematologic activity was quantified on a 0-3 visual analog scale (VAS). An organ-specific flare was defined as an increase in VAS of ≥1 point compared to the previous visit. Spatiotemporal clusters were detected using SaTScan software. Regression models were used for cluster adjustment and included individual, county-level, and environmental variables. RESULTS: Significant clusters unadjusted for environmental variables were identified for joint flares (P < 0.05; n = 3), rash flares (P < 0.05; n = 4), hematologic flares (P < 0.05; n = 3), neurologic flares (P < 0.05; n = 2), renal flares (P < 0.001; n = 4), serositis (P < 0.001; n = 2), and pulmonary flares (P < 0.001; n = 2). The majority of the clusters identified changed in significance, temporal extent, or spatial extent after adjustment for environmental variables. CONCLUSION: We describe the first spatiotemporal clusters of lupus organ-specific flares. Seasonal, as well as multi-year, cluster patterns were identified, differing in extent and location for the various organ-specific flare types. Further studies focusing on each individual organ-specific flare are needed to better understand the driving forces behind these observed changes.

Relationship Between Muscle Oxygen Saturation and Exercise Load in Patients with Malignant Hematopoietic Disease.

Our previous research confirmed that patients with malignant hematopoietic disease already had a low hemoglobin level before allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, no study has determined whether a correlation exists between exercise load, hemoglobin level, and muscle oxygen saturation (SmO2), during exercise. Therefore, the purpose of this study was to investigate whether near-infrared spectroscopy (NIRS)-derived SmO2 is associated with exercise load, as determined by a dynamometer, before allo-HSCT. This study included 19 male patients who received allo-HSCT in Hyogo College of Medicine Hospital (Japan) between November 2009 and October 2012. Patients performed isometric repeated dorsiflexion at 50% maximum voluntary contraction for 180 s to determine exercise load, and SmO2 was evaluated during exercise at the same time using NIRS (BOM-L1TRW, Omega Wave, Inc., Japan). The hemoglobin level was also evaluated before allo-HSCT. Patients with hematopoietic disease before allo-HSCT already had a low hemoglobin level. There was a significant correlation between exercise load and ∆SmO2; however, the hemoglobin level was not correlated with exercise load. In these patients, exercise load might be affected by muscle oxygen consumption rather than by the hemoglobin level. This finding shows that NIRS can used to assess fatigue in patients with malignant hematopoietic disease.

Alteraciones de la motilidad ocular en el síndrome de Kabuki / Changes in ocular motility in Kabuki síndrome

El síndrome de Kabuki es una enfermedad genética rara debida a una mutación genética en los genes KMT2D y KDM6A, que afecta a múltiples órganos, entre ellos los ojos, en la mayoría de los pacientes. Las características clínicas más típicas son: facies peculiar, baja estatura, anormalidades esqueléticas y bajo coeficiente intelectual. Las manifestaciones oculares más frecuentes son el estrabismo, la ptosis y los defectos refractivos. Presentamos una serie de casos de 5 pacientes (3 mujeres), 4 de ellos con estrabismo en forma de esotropía, hiperacción de oblicuos inferiores e hipofunción de oblicuos superiores asociado a un síndrome V. Son pocos los casos publicados de síndrome de Kabuki que describan las afectaciones oftalmológicas y las estrabológicas. Podría ser conveniente la realización de resonancias magnéticas orbitarias para detectar cambios en los trayectos musculares que estén relacionados con la patología de los movimientos oculares encontrados

Kabuki syndrome is a rare genetic disorder, caused by mutation in the KMT2D or KDM6A genes, which affects several organs in the majority of patients, among which are the eyes. The most typical clinical characteristics are mental retardation, postnatal growth retardation, skeletal anomalies, and characteristic facial features. As the eyes are affected in most of the cases, ophthalmological examination is recommended for the early detection of ocular anomalies, in order to prevent visual impairment. The most frequent ocular signs are strabismus, ptosis, and refractive anomalies. A series of cases of Kabuki syndrome is described in five children, four of whom exhibited strabismus with esotropia, over action of inferior oblique muscles, and under action of superior oblique muscles associated with a V pattern. Most published papers do not report or might underestimate the ocular problems. It may be appropriate to perform orbital magnetic resonances in order to detect changes in the muscle paths that are related to the pathology of the eye movements found