Vulnerability to Meningococcal Disease in Immunodeficiency Due to a Novel Pathogenic Missense Variant in NFKB1

NF-κB1 deficiency is suggested to be the most common cause of common variable immunodeficiency (CVID). NFKB1 encodes for the p105 precursor protein of NF-κB1, which is converted into the active transcriptional subunit p50 through proteasomal processing of its C-terminal half upon stimulation and is implicated in the canonical NF-kB pathway. Rare monoallelic NFKB1 variants have been shown to cause (haplo) insufficiency. Our report describes a novel NFKB1 missense variant (c.691C>T, p.R230C; allele frequency 0.00004953) in a family vulnerable to meningitis, sepsis, and late-onset hypogammaglobulinemia. We investigated the pathogenic relevance of this variant by lymphocyte stimulation, immunophenotyping, overexpression study and immunoblotting. The ectopic expression of p50 for c.691 C>T restricted transcriptionally active p50 in the cytoplasm, and immunoblotting revealed reduced p105/50 expression. This study shows that the deleterious missense variant in NFKB1 adversely affects the transcriptional and translational activity of NFκB1, impairing its function. Patients immunological parameters show a progressive course of hypogammaglobulinemia, which may partially account for the incomplete disease penetrance and suggest the need for closer immunological monitoring of those mutation carriers.

Listeriosis: the review of a problem, presentation of a clinical case of listeria sepsis in a 4-month child

Listeriosis is an infectious disease caused by Listeria monocytogenes microorganisms. A human can catch an infection through fecal-oral, aerogenous, or transplacental route. The listeriosis incidence in Ukraine is sporadic, single cases are not related to each other. Listeriosis is characterized by a high rate of mortality and polymorphism of clinical manifestations. The symptoms of the disease are multiple-organ: damage to the central nervous system, septic symptoms, aborts, mastitis; listeriosis can also be subclinical. The disorders of the central nervous system are associated with meningitis, meningoencephalitis, or brain abscess. The importance of the problem of diagnosis and treatment of listeriosis derived from the disease sporadicity, polymorphism of its manifestations, difficulties in etiological verification of the diagnosis. The case described is specific due to the diagnostic mistake: a child was not diagnosed with sepsis. Listeriosis in this child had a progressive course with sepsis development. Listeriosis is a rare infection, therefore it was difficult to suggest this particular infection intra vitam.

Malignant Keratitis Caused by a Highly-Resistant Strain of Fusarium Tonkinense from the Fusarium Solani Complex

Fusarium spp. are moulds ubiquitously distributed in nature and only occasionally pathogenic for humans. Species of the Fusarium solani complex are the predominant keratitis-inducing pathogens, because they are endowed with proper virulence factors. These fungi can adhere to the cornea creating a biofilm and, with the help of enzymes and cytotoxins, penetrate the cornea. Whereas an intact cornea is hardly able to be invaded by Fusarium spp. in spite of appropriate virulence factors, these opportunistic fungi may profit from predisposing conditions, for example mechanical injuries. This can lead to a progressive course of corneal infection and may finally affect the whole eye up to the need for enucleation. Here, we present and discuss the clinical, microbiological and histopathological aspects of a particular case due to Fusarium tonkinense of the Fusarium solani complex with severe consequences in a patient without any obvious predisposing factors. A broad portfolio of antifungal agents was applied, both topically and systemically as well as two penetrating keratoplasties were performed. The exact determination of the etiologic agent of the fungal infection proved likewise to be very challenging.

Subacute Thyroiditis Post-Covid-19 Infection: A Case Report

Background: Subacute thyroiditis (SAT) or granulomatous thyroiditis is usually a self-limiting inflammatory condition. The clinical presentation varies from person to person, but is usually associated with pain and systemic symptoms. Case Report: Herein, a case of a previously healthy 40 years old male who presented with unilateral right neck pain of gradual onset and progressive course has been described. The patient had recovered from a symptomatic Covid-19 infection 5 months back. The clinical examination, imaging and histopathological examination were consistent with the clinical diagnosis of subacute thyroiditis. The patient received medication in the form of pain killer, Celebrex and paracetamol, without corticosteroids, and completely recovered. Conclusion: The possibility of subacute thyroiditis post-COVID-19 infection should be considered.

The significance of time stages in different types of multiple sclerosis course for the formation of prognosis

Background. The purpose was to develop a prognosis assessment system based on clinical and mathematical analysis of indicators at different stages in various types of the course of multiple sclerosis. Materials and methods. Clinical (clinical neurological method and survey using a questionnaire developed at the Department of Autoimmune and Degenerative Pathology of the Nervous System of the State Institution “Institute of Neurology, Psychiatry and Narcology of the National Academy of Medical Sciences of Ukraine”) and mathematical and statistical (permutation test) methods were applied. Using the method of permutation (permutation test) in groups of patients with different types of multiple sclerosis, the differences in the mean values of clinical indicators were evaluated characterizing the type of multiple sclerosis course at different time stages: preclinical stage, the onset, recurrent stage for relapsing-remitting and secondary progressive multiple sclerosis, stage of progression — for secondary and primary progressive multiple sclerosis. On this basis, clinical indicators were identified, which with a high probability (confidence interval of 0.95) at each time stage of multiple sclerosis determine the final prognosis of the disease. Results. We have examined 280 patients: 80 (50 women and 30 men) with a relapsing-remitting course, 140 (80 women and 60 men) with a secondary progressive course and 60 (30 women and 30 men) with a primary progressive course of multiple sclerosis. The nature of prognosis (good and uncertain with a relapsing-remitting course, uncertain and poor with progressive types) was assessed on the basis of clinical and diagnostic criteria developed taking into account the features of the disease course as a whole. The studies have shown that a good prognosis is highly probable with a combination of clinical indicators such as mild onset, complete remission after onset, mild relapses developing rapidly, and long-term remission between relapses at a relapsing-remitting stage; uncertain prognosis — in the presence of moderate onset, stem symptoms at the onset, severe and moderate relapses, and a tendency to aggravate and lengthen relapses at a relapsing-remitting stage. A poor prognosis in a secondary progressive course is reliably associated with the chickenpox at the preclinical stage in a premorbid history, lightning-fast onset development, steady progression proceeding without clinically outlined periods of stabilization; uncertain prognosis — with a fast development of the onset. A poor prognosis in a primary progressive course was closely associated with severe traumatic brain injury at the preclinical stage in a premorbid history, cerebellar symptoms at the onset, formation of the progression stage immediately after the onset, without the stabilization period, steady type of progression at the stage of progression; uncertain prognosis — with herpetic infections at the preclinical stage in a premorbid history, mild onset, the formation of a progression stage after a stabilization period that occurred after the onset, incremental progression at the progression stage proceeding in the form of alternating periods of slow accumulation of neurological deficit, which, as a rule, has a local focus, and stages of stabilization with different duration. Conclusions. Thus, with the help of clinical and mathematical analysis, it was shown that the formation of alternative prognosis variants for different types of multiple sclerosis occurs through a selective involvement in a single pattern of clinical indicators that have diagnostic significance at different time stages of the course of the disease.

Progressive Clinical and Neuroradiological Findings in a Child with BCL11B Missense Mutation: Expanding the Phenotypic Spectrum of Related Disorder

We report a patient affected by BCL11B-related disorder, providing the first extensive demonstration of clinical and neuroradiological progressive course of the disease, with possible implications on the way it is studied and followed-up. Never described clinical aspects such as toes abnormalities and hypospadias widen the range of dysmorphisms associated with this condition. Our data suggest that BCL11B mutations may be implicated not only in impaired morphogenesis and hematopoiesis but also in progressive central nervous system damage, which remains to be further investigated and clarified.

Parkinsonism and Related Dementias

The differential diagnosis for dementia is wide. A slowly progressive course for parkinsonism suggests a degenerative cause and helps to narrow the differential diagnosis considerably. In patients with dementia in combination with parkinsonism (often collectively termed the parkinsonism-related dementias), the 4 most common neurodegenerative entities are 1) Lewy body dementias (which include dementia with Lewy bodies and Parkinson disease with dementia); 2) corticobasal syndrome or corticobasal degeneration; 3) Richardson syndrome or progressive supranuclear palsy; and 4) frontotemporal dementia with parkinsonism.

Selecting the surgical treatment for patients with diaphragmatic hernia

Hernias of the diaphragm (HAP) are a common pathology that negatively affects the patients’ quality of life and in some cases requires high-quality surgical correction. This pathology has a progressive course, which leads to an increase in the severity of clinical manifestations with the age of the patient. At present, behavioral and conservative therapy is the first line of treatment for HAP, while surgical correction is performed only if they are ineffective. This tactic helps to reduce the likelihood of discrediting surgical treatment and increase its effectiveness. The article presents the experience of surgical treatment of HAP on the basis of general surgery clinics of the N.N. Burdenko MMCH of the Ministry of Defense of the Russian Federation.

Clinical and Imaging Features of Patients With Encephalitic Symptoms and Myelin Oligodendrocyte Glycoprotein Antibodies

BackgroundMyelin oligodendrocyte glycoprotein-antibody (MOG-ab)-associated disease (MOGAD) has highly heterogenous clinical and imaging presentations, in which encephalitis is an important phenotype. In recent years, some atypical presentations in MOG-ab-associated encephalitis (MOG-E) have been increasingly reported but have not yet been described well. The aim of the study was to describe the clinical and imaging features of patients with MOG-E in our center. Atypical phenotypes would be reported, which is expected to expand the spectrum of MOGAD.MethodsWe reviewed medical records of 59 patients with MOGAD diagnosed in our center and identified cases who had ever experienced encephalitic symptoms. Three hundred ten patients with autoimmune encephalitis (AE) were also reviewed, and cases with positive MOG-ab were identified. Besides, patients with chronically progressive encephalitis were identified from 13 MOG-E and 310 AE patients. We collected demographic, clinical, laboratory, radiological, and outcome data to explore clinical and imaging characteristics in MOG-E, especially in the atypical phenotype of chronically progressive encephalitis.ResultsWe identified 13 patients (7 males, 6 females) with MOG-E. The median age at onset was 33 years (range 13~62 years). Most (9/13, 69.2%) of patients showed acute or subacute onset of encephalitic symptoms. Brain MRI abnormalities were observed in all patients. The most common lesion locations on MRI were cortical/subcortical (11/13, 84.6%), deep/periventricular white matter (10/13, 76.9%) and corpus callosum (4/13, 30.8%). Brain MRI patterns were categorized into four phenotypes. The most common pattern was cortical encephalitis with leptomeningeal enhancement/brain atrophy (10/13, 76.9%). Eight (8/13, 61.5%) patients had a good response to immunotherapy. Four (4/13, 30.8%) patients with chronically progressive course were identified from MOG-E cohort. They showed leukodystrophy-like pattern, multifocal hazy lesions, or cortical encephalitis on MRI. With immunotherapy, they only showed mild or no improvement. We also identified four (4/310, 1.3%) patients with chronically progressive course from AE cohort. They had better outcomes than counterparts in MOG-E.ConclusionsThis study demonstrates that encephalitic presentations in MOGAD had complex clinical patterns. Chronically progressive encephalitis may be a new phenotype of MOGAD. We recommend to test MOG-ab in subacute and chronic progressive dementia with leukodystrophy-like MRI lesions.

ROLE OF SONOMAMMOGRAPHY IN MONITORING THE RESPONSE OF NEOADJUVANT CHEMOTHERAPY IN MALIGNANT BREAST MASSES

Background Breast cancer is a leading cause of death and disability between women, particularly young women, in low- and average -income countries (Porter, 2018). Neoadjuvant chemotherapy (NAC) is increasingly used in management patients with locally advanced breast cancer (LABC) (Mougalian et al., 2015). Mammography and breast ultrasound are the most widest diagnostic techniques used to evaluate primary tumor size and character at the time of diagnosis and monitoring the response to NAC (Kald et al., 2015). Aim of the work The purpose of this study is to assess and evaluate the role and the accuracy of Mammography and breast ultrasound modalities in monitoring the response of the breast cancer to the neoadjuvant chemotherapy. Patients and methods Twenty three patients presenting with pathologically proven malignant mass and conducted for neoadjuvant chemotherapy with age above 40 years-old. They were referred to the radiology department (mammography unit, Ultrasound unit and MRI unit) at El Salam oncology center, during the period between December 2018 to June 2019. Once a patient satisfied the inclusion and exclusion criteria for this study, an elaborate history was taken from all the patients which was followed by a thorough clinical evaluation, in which duration of symptoms, affected side, affected breast and family history. Patients were subjected to evaluation before starting neoadjunant chemotherapy by mammography, ultrasound and MRI as well as after finishing the neoadjuvant cycles which usually was ranging 3-4 cycles. Results Total of 23 patients with breast cancer were enrolled in this study. The patients were in the age group of 41-70 years with mean age of 54 years. Majority of patients had infiltrative ductal carcinoma IDC (16 cases -69.56% and the rest of cases were infiltrative lobular carcinoma (9 cases -39.13 %). After monitoring the response of the cases to neoadjuvant chemotherapy the results showed significant regressive course to the majority of cases ( 17 cases ) (73.91%) with the rest non respondent cases divided to cases with stationary ( 3 cases ) (13.04% ) and cases with progressive course ( 3 cases ) (13.04% ). The comparison between the results of Sonomammographic assessment of the breast lesions before and after the neoadjuvant chemotherapy cycles and also to MRI show close results. There were 5 cases that showed non-respondent (including stationary course and progressive course) in both Sonomammography and MRI and only one case that was respondent according to Sonomammography and non-respondent according to MRI breast (false +e). On the other hand there were 16 cases that had showed respondent fashion in both Sonomammography and MRI. Also there was one case that had showed non-respondent course according to Sonomammography and was respondent according to MRI results (false –ve). Sonomammography sensitivity was 94.12 % and specificity was 83.33% compared to MRI results, with high accuracy value reaching to 91.30 %. Conclusion The ability of mammography and breast ultrasound to accurately measure residual tumor size following neoadjuvant chemotherapy compared to Breast MRI measurement of the residual tumor demonstrated sensitivity of 94.12 % and specificity of 83.33% with high accuracy value reaching to 91.30 %. Even that the MRI is proved to be of high accuracy in detecting residual tumor, sonomammographic imaging isa cost-effective imaging modality than the MRI with sensitivity and specificity near to that of MRI.