Alternating Hemiplegia of Childhood in a Child Harboring a Novel TBC1D24 Mutation: Case Report and Literature Review

Alternating Hemiplegia of Childhood (AHC) is a rare neurological disease characterized by early-onset recurrent paroxysmal events and persistent neurological deficits. TBC1D24 gene variants have been associated with a phenotypic spectrum having epilepsy as the main clinical manifestation. Herein, we report the case of a child affected by developmental delay, polymorphic seizures, and nonepileptic episodes characterized by hemiplegia or bilateral plegia, pallor, hypotonia, and dystonic postures without loss of consciousness that resolved with sleep. Noteworthy, the patient fulfills all the diagnostic criteria for AHC. An epilepsy gene panel revealed a novel TBC1D24 mutation. This variant may be considered a PM5, according to the American College of Medical Genetics and Genomics guidelines. TBC1D24 gene variants are associated with various clinical features, and increasing data confirms the association with permanent and paroxysmal movement disorders. Our report suggests that the TBC1D24 molecular analysis could be considered in the diagnostic workup of AHC patients.

Modern approach to the diagnosis and treatment of thrombocytopenia

Normally, the number of platelets in a healthy adult is in the range of 150-320 x 10⁹. A condition in which their number falls below 150x10⁹ is called thrombocytopenia. It can be both associated with a violation of the process of platelet formation in the bone marrow (in particular, with aplastic anemia, hemoblastosis, thrombocytopenic purpura), and be a concomitant pathology, for example, be a consequence of drug treatment of a number of somatic diseases. In the pathogenesis of thrombocytopenia, three main directions are distinguished: a decrease in platelet production, an acceleration of their decay and a violation of the distribution of the platelet pool with their sequestration in the spleen. Most often, drug thrombocytopenia develops against the background of the use of cytostatics, chloramphenicol, antithyroid drugs, NSAIDs. The decrease in the number of platelets can also be influenced by the regular use of alcohol, some infectious diseases, and immunodeficiency states. The main clinical manifestation of thrombocytopenia is hemorrhagic syndrome, proceeding as petechial rashes or ecchymosis, however, in some cases, clinical manifestations may be absent, and then the diagnosis is made on the basis of a clinical blood test. Treatment of thrombocytopenia is carried out taking into account the etiological factor that caused it.

S-Methyl-L-Ergothioneine to L-Ergothioneine Ratio in Urine Is a Marker of Cystine Lithiasis in a Cystinuria Mouse Model

Cystinuria, a rare inherited aminoaciduria condition, is characterized by the hyperexcretion of cystine, ornithine, lysine, and arginine. Its main clinical manifestation is cystine stone formation in the urinary tract, being responsible for 1–2% total and 6–8% pediatric lithiasis. Cystinuria patients suffer from recurrent lithiasic episodes that might end in surgical interventions, progressive renal functional deterioration, and kidney loss. Cystinuria is monitored for the presence of urinary cystine stones by crystalluria, imaging techniques or urinary cystine capacity; all with limited predicting capabilities. We analyzed blood and urine levels of the natural antioxidant L-ergothioneine in a Type B cystinuria mouse model, and urine levels of its metabolic product S-methyl-L-ergothioneine, in both male and female mice at two different ages and with different lithiasic phenotype. Urinary levels of S-methyl-L-ergothioneine showed differences related to age, gender and lithiasic phenotype. Once normalized by L-ergothioneine to account for interindividual differences, the S-methyl-L-ergothioneine to L-ergothioneine urinary ratio discriminated between cystine lithiasic phenotypes. Urine S-methyl-L-ergothioneine to L-ergothioneine ratio could be easily determined in urine and, as being capable of discriminating between cystine lithiasis phenotypes, it could be used as a lithiasis biomarker in cystinuria patient management.

Clinical manifestations of pseudomembranous colitis

Pseudomembranous colitis is a pathological condition in which there is damage to the mucous membrane of the large intestine with focal or diffuse fibrin depositions resulting from exposure to factors of the pathogenicity of Clostridium difficile. This disease has become quite widespread in recent years. The widespread and not always properly controlled prescription of antibiotics can lead to the development of a serious complication caused by this pathogen. The pathological condition develops against the background or after the end of the ongoing antibiotic therapy; its initial manifestation is antibiotic-associated diarrhea (AAD). Most often, this condition is diagnosed in postoperative patients against the background of a general decrease in immunity, as well as as a result of prolonged and uncontrolled intake of antibiotics. It has been proven that the frequency of Clostridium difficile colonization increases sharply during hospitalization, thus, this infection was referred to hospital ones. The main clinical manifestation of pseudomembranous colitis is diarrhea; stool can become more frequent, up to 5-7 times a day, while feces are scanty and not abundant. In addition to diarrhea, abdominal pain and flatulence may occur. The diagnosis is established on the basis of the fact of increased stool within two or more days for 8 weeks after taking antibiotics confirmed by the patient.

FEATURES OF THE CLINICAL COURSE OF MEMBRANOUS NEPHROPATHY

Мембранозная нефропатия является иммунологически обусловленной не воспалительной гломерулопатией, имеет прогрессирующее стадийное течение и характеризуется дистрофическими и склеротическими процессами. Мембранозная нефропатия - это поражение почечных клубочков (основные функциональные единицы почек), возникающее вследствие оседания на стенках почечных капилляров иммунных комплексов. Это приводит к утолщению и дальнейшему расслоению базальных мембран и стенок сосудов в клубочках. Основным клиническим проявлением МН является нефротический синдром (отеки по всему телу, наличие белка в моче и высокий холестерин в крови). Membranous nephropathy is an immunologically determined non-inflammatory glomerulopathy, has a progressive stage course and is characterized by dystrophic and sclerotic processes. Membranous nephropathy is a lesion of the renal glomeruli (the main functional units of the kidneys) that occurs due to the settling of immune complexes on the walls of the renal capillaries. This leads to thickening and further delamination of the basal membranes and vascular walls in the glomeruli. The main clinical manifestation of MN is nephrotic syndrome (edema throughout the body, the presence of protein in the urine and high cholesterol in the blood).

Multiple endocrine neoplasia syndrome

Background. Multiple endocrine neoplasia type 1 is a rare inherited disease that combines heterogeneous autosomal inherited disorders, the pathogenesis of which is based on hyperplasia or tumor transformation of several neuro- endocrine glands. In this pathology, treatment protocols are insufficient. Surgical treatment, suppressive or replacement therapy, radiation and chemotherapy are mainly used. We presented a successful experience of combined radiotherapy of multiple pancreatic insulinoma as the main clinical manifestation of the syndrome of multiple endocrine neoplasia. The combination of intra-tissue brachytherapy and megavolt remote therapy in TFD, isoeffective 50 Gy, allowed to achieve reliable control of hypoglycemic attacks within 2 years of follow-up. Purpose – to acquaint the medical community with successful experience of combined radiation treatment of multiple pancreatic insulinoma as a main clinical manifestation of the multiple endocrine neoplasia syndrome. Materials and Methods. Clinical case of patient L., 30 years old, who received combined radiation therapy for clinically significant manifestations of hormonally active multiple insulinoma of the pancreas in the Department of Radiological Oncology of State Organization «Grigoriev Institute for Medical Radiology and Oncology of the National Academy of Medical Sciences of Ukraine». Results. In May 2019, palliative contact brachytherapy was performed on the MULTISOURCE device. Total focal dose (TFD) for cells in the pancreas GENUS 3 Gy 5 times a week, TFD 18 Gy. At the end of brachytherapy, attacks of hypoclycemia were stopped. In March 2020, remote radiation therapy was performed on a linear accelerator CLINAC-600C (6MeV) in the mode of classical fractionation (single focal dose (SFD) 1.8 Gy 5 times a week), TFD for the entire volume of the pancreas 30.6 Gy. In May 2021, CT scan showed that the process in the pancreas was stabilized, but in connection with the resumption of hypoglycemia and the emergence of dyshormonal osteopathy, a course of remote radiation therapy for the entire pancreas, SFD 1.8 Gy, TFD 20 Gy simultaneously with the introduction of bisphosphonates. Conclusions. Our patient demonstrates type I syndrome of multiple neo- plasms, neuroendocrine tumor of pancreas G1 T3N0M0 IIB stage. Due to multi-stage combined radiation therapy for 2 years it is possible to achieve stabilization of the process and reliable control of hypoglycemic attacks, which indicates the effectiveness of this method as an alternative to surgery in unresectable cases.

Current Perspective of Hydrogen Sulfide as a Novel Gaseous Modulator of Oxidative Stress in Glaucoma

Glaucoma is a group of diseases characterized by the progressive loss of retinal ganglion cells and their axons. Elevated intraocular pressure (IOP) is the main clinical manifestation of glaucoma. Despite being in the focus of the studies for decades, the characteristic and the exact pathology of neurodegeneration in glaucoma remains unclear. Oxidative stress is believed to be one of the main risk factors in neurodegeneration, especially its damage to the retinal ganglion cells. Hydrogen sulfide (H2S), the recently recognized gas signaling molecule, plays a pivotal role in the nervous system, vascular system, and immune system. It has also shown properties in regulating oxidative stress through different pathways in vivo. In this review, we summarize the distribution and the properties of H2S within the eye with an emphasis on its role in modulating oxidative stress in glaucoma.

Geographic Distribution of the Prevalence of Neurocysticercosis in the Municipality of Piedade, São Paulo

Background: Neurocysticercosis is a globally occurring parasitosis that affects the central nervous system. The main clinical manifestation is seizures.The aim of this study was to analyze the geographic distribution of patients with seizures attending the Emergency Unit of the Piedade municipality, SP, with a diagnosis of neurocysticercosis, and to compare the association of its prevalence with age, basic sanitation and food hygiene habits between rural and urban areas. Methods: One hundred thirty-six patients with seizures were evaluated. The Epidemiological data of all subjects will be described. Results: The diagnosis of neurocysticercosis was confirmed in 24 patients, corresponding to a prevalence of 17.65%. The presence of an open sewer predominated in the rural area, while the consumption of unwashed fruits, presence of elderly people and geographic distribution were similar in the two areas. Conclusions: Urgent measures to raise awareness about the disease and preventive actions should be taken by world authorities.