Idiopathic Form Research Articles

Isolated Severe Neutropenia in Adults, Evaluation of Underlying Causes and Outcomes, Real-World Data Collected over a 5-Year Period in a Tertiary Referral Hospital.

Background and Objectives: In clinical practice, neutropenia is frequently accompanied by other cytopenia; isolated non-chemotherapy-induced severe neutropenia is less frequent and its differential diagnosis can be challenging. In this real-world study with data collected over a 5-year period in a tertiary referral hospital, we primarily sought to identify underlying causes of isolated severe neutropenia (<0.5 × 109/L). Secondly, we aimed to analyze its management and outcomes. Materials and Methods: From 444,926 screened patients, after exclusion of patients with chemotherapy, radiotherapy, hematological neoplasms, additional cytopenia, and benign ethnic neutropenia, we identified and analyzed data from 70 patients (0.015%) with isolated severe neutropenia. We thus confirmed that the occurrence of isolated severe neutropenia is a rare event, even in a tertiary hospital. Results: The median age at diagnosis was 34 years (range 1-81) and 65% were female. Acute neutropenia was more frequently observed (n = 46/70, 65.7%); the main underlying causes in this group were drugs (n = 36/46, 78%) followed by infections (n = 10/46, 21.7%). We identified 24 (34.3%) patients with chronic neutropenia. The majority of them (n = 12/24, 50%) had an idiopathic form (CIN), 8/24 (33%) were autoimmune (AIN), and 4/24 (17%) were congenital. Conclusions: This study demonstrates the rarity and heterogeneity of isolated severe neutropenia and the steps to consider in its diagnostic work-up and management. Epidemiological characteristics, diagnostic work-up, and management including hospitalizations are described. Due to the high frequency of metamizole-induced neutropenia observed in this study, we want to raise awareness about its use, since this complication generates frequent hospitalizations even in young, otherwise healthy patients. Furthermore, recurrent infections in chronic forms of idiopathic neutropenia were quite common, suggesting a difference in phenotypes and need for therapy consideration depending on the clinical course.

Idiopathic enterocolic intussusception: imaging findings in an abdominal emergency

Adult intussusceptions are a rare cause of abdominal obstruction and are usually associated with a neoplastic disease; idiopathic forms are extremely rare. We report a case of enterocolic intussusception in a young woman who experienced symptoms of abdominal obstruction. Imaging findings were reported. On histological examination, no underlying diseases were found. The patient presented at the hospital for computed tomography because of persistent abdominal pain. Computed tomography revealed an enterocolic invagination involving the ileocecal valve and cecum and widespread edematous thickening of the colonic parietal walls. Idiopathic enterocolic intussusception is an uncommon abdominal urgency in adults. Symptoms can be vague and persistent, delaying an accurate diagnosis. Imaging is crucial in these circumstances to make a diagnosis. Some computed tomography findings, such as a target-like bulk, may be suggestive.

Definition and diagnosis of Parkinson’s disease: guideline “Parkinson’s disease” of the German Society of Neurology

Abstract Background Accurate definition and operational criteria for diagnosing Parkinson’s disease (PD) are crucial for evidence-based, patient-centered care. Objective To offer evidence-based recommendations for defining and diagnosing PD, incorporating contemporary clinical, imaging, biomarker, and genetic insights. Methods The guideline development began with the steering committee establishing key PICO (patient, intervention, comparison, outcome) questions, which were refined by the coauthors. Systematic literature searches identified relevant studies, reviews, and meta-analyses. Recommendations were drafted, evaluated, optimized, and voted upon by the German Parkinson’s Guideline Group. Results Parkinson’s disease (PD) is now understood to encompass a broader spectrum of etiologies than previously recognized. Advances in molecular pathogenesis, neuroimaging, and early clinical phenotypes suggest that PD is not a uniform disease entity and is often not idiopathic. This necessitates an updated framework for PD definition and diagnosis. The German Society for Neurology now endorses a broader concept of PD, incorporating both idiopathic and hereditary forms, as opposed to the previously narrower concept of “idiopathic Parkinson syndrome.” The revised guidelines recommend using the 2015 Movement Disorders Society diagnostic criteria, emphasize the importance of long-term clinical follow-up for improved diagnostic accuracy, and highlight the significance of non-motor symptoms in clinical diagnosis. Specific recommendations are provided for the use of imaging and fluid biomarkers and genetic testing to support the clinical diagnosis. Conclusion The updated guidelines from the German Society for Neurology enhance diagnostic accuracy for PD, promoting optimized clinical care.

FP4.12 - Enterocolic lymphocytic phlebitis masquerading as a malignant stricture in the cecum

Abstract Introduction Enterocolic lymphocytic phlebitis (ELP) is an idiopathic form of venous inflammation which is limited to the gastrointestinal tract. It is characterised by inflammation of the veins with no involvement of the arteries. Usually, It presents with gastrointestinal symptoms such as abdominal pain, and imaging may suggest malignancy. Case history A 56-year-old woman presented with fresh blood in her stools, abdominal pain and diarrhoea. All blood tests were normal; however, she had a raised CRP of 105 mg/L (normal &amp;lt; 5 mg/L). CT abdomen and pelvis showed thickening in the transverse colon and intussusception of the terminal ileum into the caecum. She was treated conservatively and discharged when symptoms resolved with an outpatient colonoscopy. The colonoscopy was incomplete due to an unresolvable sigmoid loop; CT colonography showed caecal wall thickening, which was suggestive of caecal malignancy. Following the MDT discussion, the patient was booked for a right hemi-colectomy. The right hemicolectomy specimen histology showed no malignancy, and lymphocytic phlebitis of the submucosal, subserosa and mesenteric veins, but the arteries were normal; hence, a diagnosis of enterocolic lymphocytic phlebitis was made. Conclusion ELP is a rare idiopathic form of venous inflammation localised to the gastrointestinal tract, which can occasionally present similar to bowel malignancy. The diagnosis is usually confirmed with a histopathology assessment. We present this case in light of its rarity to add to the literature on this entity.

Diagnostic challenges in patients with Castleman disease, a single center experience from Hungary.

Castleman disease is a rare and atypical lymphoproliferative disorder characterized by diverse clinical manifestations. It has both unicentric and multicentric forms, the latter with further subdivisions, i.e., human herpesvirus 8-associated and idiopathic forms. The diagnosis of Castleman disease is often delayed, as it is rare, and because it shares clinical features with different autoimmune, inflammatory, and malignant lymphoproliferative disorders. The first-line treatment in unicentric form is mainly surgical, while in idiopathic Castleman disease, anti-interleukin-6 treatment is the therapy of choice. In virus-associated diseases, antiretroviral therapy and rituximab are recommended. In Hungary, only a few cases of Castleman disease have been published. This report presents our twodecades of experience in the challenging diagnosis and management of this rare disorder, most properly underdiagnosed in Hungary. We provide insights into seven unicentric and five idiopathic multicentric Castleman disease cases, the latter ones especially highlighting the diagnostic and therapeutic challenges due to the variable and unique clinical features both of patients and diseases, e.g., bronchiolitis obliterans, stage IV diabetic renal failure, anti-HBc positivity, siltuximab treatment period, respectively.

Novel Advances in Cell-Free Therapy for Premature Ovarian Failure (POF): A Comprehensive Review

Premature ovarian failure (POF), is a condition characterized by the early decline of ovulation function. POF is a complex disorder that can be caused by various factors, and the idiopathic form represents a significant proportion of POF patients. Hormone replacement therapy (HRT) is currently considered the first-line treatment for POF. This review aims to provide a comprehensive overview of recent advancements in platelet-rich plasma (PRP), in vitro activation (IVA), stem cell (SC) therapy, exosome therapy, microRNAs, and mitochondrial targeting therapies as a promising cell-free therapeutic approach in reproductive medicine. PLT-Exos, a new generation of cells, has been used to treat POF for more than a decade and has been shown to attenuate oocyte morphology and promote the differentiation of theca cells through the upregulation of PI3K/Akt and Bcl2, as well as the downregulation of the Smad and Bax signaling pathways. This review summarizes the current state of the art in the field of PLT-Exos and discusses the advantages and limitations of their potential clinical applications.

Idiopathic male infertility – what are we missing?

ABSTRACT Couple’s infertility is a rising issue worldwide affecting approximately 15% of couples. In 50% of the couples, a male factor infertility can be identified. Moreover, 30% of the men exhibit reduced sperm quality without any identifiable reason, thereby delineating the condition of idiopathic male infertility (IMI). Despite numerous improvements in the diagnosis and treatment of male infertility over the last decades, idiopathic forms are still the most challenging clinical dilemmas. The aim of this article is to describe the comprehensive diagnostic work-up that each idiopathic infertile man should follow. Moreover, potential new pathophysiological mechanisms and suggested treatment options are discussed. A detailed medical history and an extensive physical examination are mandatory to investigate potential treatable causes of MFI. Similarly, standard semen analysis has been proven to be limited in capturing the fecundability of the spermatozoa itself, therefore more advanced examinations, such as sperm DNA fragmentation (SDF) and oxidative stress measurement, are becoming important in clinical practice for IMI. In terms of diagnostic tools, imaging and genetic investigations are useful to classify idiopathic infertile men, however, epigenetic changes have demonstrated to have a role in sperm production and a prognostic value in fertility outcomes. Antioxidant treatment for IMI has been found to be a valid option to counteract ROS action, while gonadotropins are used to improve sperm quality and SDF. Artificial intelligence is promising to better manage idiopathic infertile men in terms of diagnosis and treatment options.

Prevalence of scoliosis in children and adolescents: a systematic review and meta-analysis.

The understanding of the prevalence and early predictive factors of scoliosis in children and adolescents is limited, which poses challenges to developing preventative strategies. This systematic review and meta-analysis aimed to clarify the prevalence and predictors of scoliosis among children and adolescents. We conducted a comprehensive search in PubMed, Cochrane, Embase, and Web of Science through October 2023. The quality of included studies was evaluated using the Joanna Briggs Institute scale or the Newcastle-Ottawa Scale. Subgroup analyses were performed to examine different types of scoliosis and specific demographic groups. From 32 studies encompassing 55,635,351 children and adolescents, we identified 284,114 cases of scoliosis, resulting in a prevalence rate of 3.1% (95% CI: 1.5%-5.2%). This rate varied by gender, degrees of scoliosis severity, and between idiopathic vs. congenital forms. Notable predictors included gender, age, Body Mass Index (BMI), race, environmental factors, and lifestyle choices. Scoliosis is a significant condition affecting a minority of children and adolescents, particularly adolescent girls and individuals who are overweight. It is recommended that guardians and schools enhance educational efforts towards its prevention. https://www.crd.york.ac.uk/, Identifier CRD42023476498.

P-055 Influence of a dynamic exposome on the genetic component of male infertility

Abstract Study question Do the genetic factors associated with idiopathic severe spermatogenic failure (SPGF) differ across age groups due to evolving environmental exposures over generations? Summary answer Dynamic changes in environmental exposures have the potential to reshape the genetic predisposition to idiopathic SPGF. What is known already Accumulating evidence suggests that the idiopathic form of SPGF may represent a complex trait with a multifactorial aetiology, wherein environmental factors influence the predisposition and development of the disease through their interaction with genetic polymorphisms. In a recent genome-wide association study (GWAS) of SPGF conducted in a European population, we identified genetic variants associated with this condition in immune and spermatogenesis-related genes. However, while GWASs serve as valuable tools for identifying susceptibility risk loci, our understanding of the influence of environmental factors and their specific impact on the genetic architecture of these conditions remains limited. Study design, size, duration Genome-wide genotype data from 912 SPGF cases and 1,360 unaffected controls from the Iberian Peninsula and Germany were analysed considering age as a proxy to assess exposure to varying environmental factors across generations. An in silico functional prioritisation of associated genomic regions was also performed to comprehensively evaluate the gene-environment relationships influencing the disease. Participants/materials, setting, methods The study cohort was stratified into two age groups: individuals aged 40 or older in 2023 (452 cases and 965 controls) and those under 40 in 2023 (460 cases and 424 controls). SPGF comprised individuals with non-obstructive azoospermia (n = 547) or non-obstructive oligozoospermia (n = 365). Logistic regression models were used for the case-control analysis, with the generation included as a covariate. Bioinformatic approaches involved the examination of functional annotations of the genome sourced from different public databases. Main results and the role of chance Thirteen genetic loci were found to be associated with idiopathic SPGF, assuming generation-dependent effects. Five of them showed a correlation with an increased susceptibility to SPGF in the youngest age group (rs72818509: P = 2.19E−05, rs57701320: P = 5.20E−05, rs79733930: P = 7.81E−05, rs77137582: P = 1.04E−04, rs75938373: P = 3.56E−05), while the remaining eight were specifically associated with the disease in the oldest age group (rs144324356: P = 2.37E−05, rs3763812: P = 8.61E−05, rs61997636: P = 1.00E−04, rs111364930: P = 9.63E−05, rs115408081: P = 5.77E-05, rs142908940: P = 1.76E−04, rs144031067: P = 1.76E-04, rs74514513: P = 1.76E-04). These associations were primarily attributed to the interaction between each lead variant and the age group. Additionally, associations were established between the identified genomic risk loci and various environmental factors, including toxic habits (such as smoking or alcohol consumption), diet-related traits (such as cholesterol levels, type 2 diabetes, and body mass index), respiratory disorders (such as asthma or COVID-19), autoimmune diseases (including systemic lupus erythematosus), and educational attainment. Our findings suggest that changes in environmental factors across generations could alter the genetic basis of idiopathic SPGF over time. Limitations, reasons for caution Despite the overall statistical power of our study cohort being suitable for detecting the expected effects, further independent studies comprising extensive cohorts across diverse ethnic populations are needed to validate the outcomes of our research. Wider implications of the findings Using a novel approach assess the potential impact of varying environmental factors on the genetic susceptibility to complex diseases, we gained insights into the intricate mechanisms underlying onset and progression of idiopathic SPGF. Understanding the etiological causes of multifactorial human disorders would help in developing personalized healthcare strategies. Trial registration number Not applicable

Idiopathic Localized Involutional Lipoatrophy Responsive to Injection Normal Saline: A Case Series

Background: Localized involutional lipoatrophy (LIL) is a rare distinctive idiopathic form of localized lipoatrophy. It is characterized by loss of adipose tissue without antecedent inflammation and was first described by Peters and Winkelmann in 1986. There have been only a few reports on LIL in the English literature. We, herein, report cases series of idiopathic LIL (ILIL) and determine the efficacy of injection normal saline in such patients. Objectives: The aim of the study was (1) to study the clinical features and evolution of lesions in patients diagnosed with ILIL and (2) to determine the efficacy of injection normal saline in such patients. Materials and Methods: It was a retrospective study conducted in the department of dermatology at a tertiary care center from May 2021 to April 2023. We included all clinically suspected cases of ILIL with characteristic histopathological findings who were treated with injection normal saline. All cases with history of antecedent injections, vaccination, or medications before the development of lesion were excluded from the study. Results: The median age of presentation was 3 years. Ten (71%) patients were male, while 4 (29%) were female. All patients had lesion on buttocks and all were unilateral. Overall, 10/14 (71%) patients responded to the treatment. Conclusions: This report demonstrates that serial saline injections provide a safe, relatively rapid, cost-effective, and uncomplicated solution to idiopathic involutional lipoatrophy.

Proteomic profiling of bronchoalveolar lavage fluid uncovers protein clusters linked to survival in idiopathic forms of interstitial lung disease

BackgroundIdiopathic interstitial pneumonias (IIPs) such as idiopathic pulmonary fibrosis (IPF) and interstitial pneumonia with autoimmune features (IPAF), present diagnostic and therapeutic challenges due to their heterogeneous nature. This study aimed to identify intrinsic molecular signatures within the lung microenvironment of these IIPs through proteomic analysis of bronchoalveolar lavage fluid (BALF).MethodsPatients with IIP (n=23) underwent comprehensive clinical evaluation including pre-treatment bronchoscopy and were compared to controls without lung disease (n=5). Proteomic profiling of BALF was conducted using label-free quantitative methods. Unsupervised cluster analyses identified protein expression profiles which were then analyzed to predict survival outcomes and investigate associated pathways.ResultsProteomic profiling successfully differentiated IIP from controls.k-means clustering, based on protein expression revealed three distinct IIP clusters, which were not associated with age, smoking history, or baseline pulmonary function. These clusters had unique survival trajectories and provided more accurate survival predictions than the Gender Age Physiology (GAP) index (C-index 0.794versus0.709). The cluster with the worst prognosis featured decreased inflammatory signaling and complement activation, with pathway analysis highlighting altered immune response pathways related to immunoglobulin production and B cell-mediated immunity.ConclusionsThe unsupervised clustering of BALF proteomics provided a novel stratification of IIP patients, with potential implications for prognostic and therapeutic targeting. The identified molecular phenotypes underscore the diversity within the IIP classification and the potential importance of personalized treatments for these conditions. Future validation in larger, multi-ethnic cohorts is essential to confirm these findings and to explore their utility in clinical decision-making for patients with IIP.

Role and predictive value of microRNAs 204 and 210 in the diagnosis of pulmonary arterial hypertension and the distinction between idiopathic, systemic sclerosis, and schistosomiasis-associated pulmonary arterial hypertension

BackgroundPulmonary arterial hypertension is most of the time diagnosed late in the course of the disease and necessitates right cardiac catheterization which is an invasive and costly tool. MicroRNAs have a role in the pathogenesis of pulmonary hypertension, systemic sclerosis, and schistosomiasis and their dosages are easy and non-expensive. Therefore, determining their levels in the blood may be helpful in detecting PAH and differentiating its idiopathic form from those caused by systemic sclerosis and schistosomiasis.Purpose of the studyTo evaluate the role of microRNA (miR) 204 and miR-210 in the diagnosis of PAH and to distinguish between idiopathic PAH (IPAH), systemic sclerosis-associated PAH (SSc-PAH), and schistosomiasis-associated PAH (Sch-PAH) and to identify patients who may benefit from simple non-expensive and non-invasive methods in diagnosis of PAH.MethodsSixty patients with PAH and 30 subjects as control were enrolled in the study. PAH was diagnosed by right heart catheterization, echocardiography, and laboratory tests. Blood samples were taken from all patients for measuring miR-204 and miR-210.ResultsMiR-204 was downregulated in PAH and there was a highly significant difference between PAH and control (p = 0.003) with cut-off predictive value ≤ 0.15 µM and 70% sensitivity, 85% specificity with AUC (0.749). However, miR-204 failed to distinguish between IPAH, SSc-PAH, and Sch-PAH. MiR-210 was upregulated in PAH with a highly significant difference between PAH and control (p < 0.001) with cut-off predictive value ≥ 1.16 µM and 93.33% sensitivity, 85% specificity with AUC (0.917). MiiR-210 showed a significant difference between SSc-PAH and idiopathic PAH (P = 0.012) and between SSc-PAH and Sch-PAH (P = 0.035).ConclusionsMiR-204 and miR-210 are useful non-invasive and non-expensive markers for the diagnosis of PAH, miR-210 is an excellent predictor in the diagnosis of PAH and also miR-210 might be used to distinguish SSc-PAH from idiopathic PAH and Sch-PAH.

Epiretinal membrane: diagnostics, indications and surgical treatment

An epiretinal membrane (ERM) is afrequently occurring disease affecting the macula, which can be associated with visual impairment and metamorphopsia, depending on the severity and location. Adistinction is made between an idiopathic form caused by age-related changes of the vitreous body and asecondary form associated with diseases of the posterior segment. The development of fibrocellular epiretinal membranes formed by dedifferentiation of intraretinal and extraretinal cells at the level of the vitreomacular interface plays amajor role in the pathogenesis. The diagnostics and indications for surgical treatment of ERM are based on the visual acuity, evidence of metamorphopsia, ophthalmoscopic findings and optical coherence tomography (OCT) of the macula. In addition to the possibility of observation of the course where benign spontaneous courses are not uncommon, pars plana vitrectomy (PPV) with peeling of the ERM and internal limiting membrane (ILM) to prevent recurrences is the treatment of choice in symptomatic patients. The prognosis after surgical treatment is very good. In approximately two thirds of the cases, an improvement in visual acuity and/or areduction of metamorphopsia can be achieved, with anumber of predictive, primarily OCT-based factors enabling a prediction of the functional prognosis. Comprehensive patient education regarding the generally long duration of postoperative rehabilitation and the possibility of persistent symptoms or visual deterioration despite successful membrane removal is essential.

Proteomic profiling of bronchoalveolar lavage fluid uncovers protein clusters linked to survival in idiopathic forms of interstitial lung disease.

Idiopathic interstitial pneumonias (IIPs) such as idiopathic pulmonary fibrosis (IPF) and interstitial pneumonia with autoimmune features (IPAF), present diagnostic and therapeutic challenges due to their heterogeneous nature. This study aimed to identify intrinsic molecular signatures within the lung microenvironment of these IIPs through proteomic analysis of bronchoalveolar lavage fluid (BALF). Patients with IIP (n=23) underwent comprehensive clinical evaluation including pre-treatment bronchoscopy and were compared to controls without lung disease (n=5). Proteomic profiling of BALF was conducted using label-free quantitative methods. Unsupervised cluster analyses identified protein expression profiles which were then analyzed to predict survival outcomes and investigate associated pathways. Proteomic profiling successfully differentiated IIP from controls. k-means clustering, based on protein expression revealed three distinct IIP clusters, which were not associated with age, smoking history, or baseline pulmonary function. These clusters had unique survival trajectories and provided more accurate survival predictions than the Gender Age Physiology (GAP) index (C-index 0.794 vs. 0.709). The cluster with the worst prognosis featured decreased inflammatory signaling and complement activation, with pathway analysis highlighting altered immune response pathways related to immunoglobulin production and B cell-mediated immunity. The unsupervised clustering of BALF proteomics provided a novel stratification of IIP patients, with potential implications for prognostic and therapeutic targeting. The identified molecular phenotypes underscore the diversity within the IIP classification and the potential importance of personalized treatments for these conditions. Future validation in larger, multi-ethnic cohorts is essential to confirm these findings and to explore their utility in clinical decision-making for patients with IIP.

Structural deviations of the posterior fossa and the cerebellum and their cognitive links in a neurodevelopmental deletion syndrome.

High-impact genetic variants associated with neurodevelopmental disorders provide biologically-defined entry points for mechanistic investigation. The 3q29 deletion (3q29Del) is one such variant, conferring a 40-100-fold increased risk for schizophrenia, as well as high risk for autism and intellectual disability. However, the mechanisms leading to neurodevelopmental disability remain largely unknown. Here, we report the first in vivo quantitative neuroimaging study in individuals with 3q29Del (N = 24) and neurotypical controls (N = 1608) using structural MRI. Given prior radiology reports of posterior fossa abnormalities in 3q29Del, we focused our investigation on the cerebellum and its tissue-types and lobules. Additionally, we compared the prevalence of cystic/cyst-like malformations of the posterior fossa between 3q29Del and controls and examined the association between neuroanatomical findings and quantitative traits to probe gene-brain-behavior relationships. 3q29Del participants had smaller cerebellar cortex volumes than controls, before and after correction for intracranial volume (ICV). An anterior-posterior gradient emerged in finer grained lobule-based and voxel-wise analyses. 3q29Del participants also had larger cerebellar white matter volumes than controls following ICV-correction and displayed elevated rates of posterior fossa arachnoid cysts and mega cisterna magna findings independent of cerebellar volume. Cerebellar white matter and subregional gray matter volumes were associated with visual-perception and visual-motor integration skills as well as IQ, while cystic/cyst-like malformations yielded no behavioral link. In summary, we find that abnormal development of cerebellar structures may represent neuroimaging-based biomarkers of cognitive and sensorimotor function in 3q29Del, adding to the growing evidence identifying cerebellar pathology as an intersection point between syndromic and idiopathic forms of neurodevelopmental disabilities.

Megalencephaly: Classification, Genetic Causes, and Related Syndromes

AbstractMegalencephaly is a developmental disorder due to an abnormal neuronal proliferation and migration during intrauterine or postnatal brain development that leads to cerebral overgrowth and neurological dysfunction. This cerebral overgrowth may affect the whole encephalon or only a region; when it involves one hemisphere it is referred to as hemimegalencephaly. Megalencephaly presents with a head circumference measurement of 2 standard deviations above the average measure for age. This group of disorders is clinically characterized by early onset and refractory to therapy epilepsy, neurodevelopmental disorders, behavioral problems, and autism spectrum disorder. Syndromic forms of megalencephaly should be considered when associated with other congenital abnormalities. Megalencephaly in fact could be associated with segmental overgrowth and cutaneous/vascular abnormalities (i.e., Proteus syndrome, CLOVES [congenital lipomatous overgrowth, vascular malformations, epidermal naevi, scoliosis, and/ or skeletal abnormalities] syndrome, Klippel-Trenaunay syndrome, megalencephaly-capillary malformation-polymicrogyria syndrome , megalencephaly-postaxial polydactyly-polymicrogyria-hydrocephalus syndrome, etc.) or generalized overgrowth (i.e., Weaver or Beckwith-Wiedemann syndrome) as well as with nanism in achondroplasia where megalencephaly is associated with disproportionate short stature, primary skeletal dysplasia, characteristic facies (prominent forehead, flat nasal bridge), narrow chest, and normal intelligence. It is possible to identify three main groups of disorders associated with megalencephaly: idiopathic or benign, metabolic, and anatomic. The idiopathic (benign) form indicates an abnormal increased head circumference in absence of neurological impairment, such as in benign familial megalencephaly. In metabolic megalencephaly (such as in organic acid disorders, metabolic leukoencephalopathies, or lysosomal diseases) there is an increase of different constituents that increase the size of the brain, whereas in the anatomical form there are underlying genetic causes. Neuroimaging is crucial for diagnosis, as it can reveal a generalized brain growth or a segmental one and possible specific frameworks associated. In all these conditions it is necessary to identify possible microdeletion-microduplication by chromosomal arrays.

Visual social attention in SYNGAP1-related intellectual disability.

SYNGAP1-ID is a neurodevelopmental disorder caused by a mutation of the SYNGAP1 gene. Characterized by moderate to severe developmental delay, it is associated with several physical and behavioral issues as well as additional diagnoses, including autism. However, it is not known whether social cognitive differences seen in SYNGAP1-ID are similar to those previously identified in idiopathic or other forms of autism. This study therefore investigated visual social attention in SYNGAP1-ID. Eye movements were recorded across three passive viewing tasks (face scanning, pop-out, and social preference) of differing social complexity in 24 individuals with SYNGAP1-ID and 12 typically developing controls. We found that SYNGAP1-ID participants looked at faces less than the controls, and when they did look at faces, they had less time looking at and fewer fixations to the eyes. For the pop-out task, where social and nonsocial objects (Phone, car, face, bird, and face-noise) were presented in an array, those with SYNGAP1-ID spent significantly less time looking at the phone stimulus as well as fewer fixations to the face compared with the typically developing controls. When looking at two naturalistic scenes side by side, one social in nature (e.g., with children present) and the other not, there were no differences between the SYNGAP1-ID group and typically developing controls on any of the examined eye tracking measures. This study provides novel findings on the social attention of those with SYNGAP1-ID and helps to provide further evidence for using eye tracking as an objective measure of the social phenotype in this population in future clinical trials.

Idiopathic Harlequin syndrome: A case report and literature review

Harlequin's syndrome is a rare dysautonomic syndrome of the face characterized by sweating with flush of one side and anhidrosis of the contralateral side. Mostly idiopathic although several secondary cases have been reported in the literature, the purpose of the treatment is mainly aesthetic and functional. We report the case of a patient having harlequin syndrome in its idiopathic form with a literature review.

Клинический случай идиопатической формы синдрома Свита

Background. Sweet’s syndrome (acute febrile neutrophilic dermatosis) is an extremely rare disease of the group of neutrophilic dermatoses with undulating courses of illness, which is an inflammatory non-infectious skin reaction characterized histopathologically by the presence of dense diffuse neutrophil infiltrate in the dermis without signs of leukocytoclastic vasculitis, edema and fragmentation of neutrophil nuclei. The mechanism of development of this disease is presumably associated with a cytokine-mediated hypersensitivity reaction followed by neutrophil infiltration of the dermis, however, the etiology of the development of this pathogenesis is not known. Sweet syndrome is a current problem, since complications can occur in the form of damage to the organs of the central nervous system, eyes, lungs, skin breakdown, as well as changes in the immune system in the form of immunodeficiency. Aim. To evaluate, describe, study the courses and complications of the idiopathic form of Sweet’s syndrome. Materials and methods. Study of examination data of a (3-year-old girld) who was being treated at the department of pulmonology of Kursk Regional Children's Clinical Hospital. Study and analysis of scientific literature on the problem of Sweet's syndrome. Conclusion. As a result of studying this Clinical case, we came to the conclusion that despite the fact that Sweet’s syndrome is an extremely rare disease and more often debuts at the age of 60, it can also be observed in children, which must be taken into account in the presence of a skin rash without a known etiology and pathogenesis. Since complications may occur, it is necessary to identify and treat exacerbations of this disease in a timely manner. The prognosis of the disease is relatively favorable, since complications of Sweet’s syndrome can lead to a decrease in the quality of life of patients.

Placental senescence pathophysiology is shared between peripartum cardiomyopathy and preeclampsia in mouse and human.

Peripartum cardiomyopathy (PPCM) is an idiopathic form of pregnancy-induced heart failure associated with preeclampsia. Circulating factors in late pregnancy are thought to contribute to both diseases, suggesting a common underlying pathophysiological process. However, what drives this process remains unclear. Using serum proteomics, we identified the senescence-associated secretory phenotype (SASP), a marker of cellular senescence associated with biological aging, as the most highly up-regulated pathway in young women with PPCM or preeclampsia. Placentas from women with preeclampsia displayed multiple markers of amplified senescence and tissue aging, as well as overall increased gene expression of 28 circulating proteins that contributed to SASP pathway enrichment in serum samples from patients with preeclampsia or PPCM. The most highly expressed placental SASP factor, activin A, was associated with cardiac dysfunction or heart failure severity in women with preeclampsia or PPCM. In a murine model of PPCM induced by cardiomyocyte-specific deletion of the gene encoding peroxisome proliferator-activated receptor γ coactivator-1α, inhibiting activin A signaling in the early postpartum period with a monoclonal antibody to the activin type II receptor improved heart function. In addition, attenuating placental senescence with the senolytic compound fisetin in late pregnancy improved cardiac function in these animals. These findings link senescence biology to cardiac dysfunction in pregnancy and help to elucidate the pathogenesis underlying cardiovascular diseases of pregnancy.