Central Nervous System Pathology Research Articles

The Effect of Short-Term Exposure to Cadmium on the Expression of Vascular Endothelial Barrier Antigen in the Developing Rat Forebrain and Cerebellum: A Computerized Quantitative Immunofluorescent Study.

Clinical and laboratory studies have shown that environmental exposure to cadmium produces damage to several organs, including bones, lungs, and kidneys. The involvement of cadmium in central nervous system (CNS) disorders has also been widely reported, but the precise pathophysiological mechanism is not yet fully understood. Children who were exposed to cadmium during pregnancy are known to suffer from developmental delays, learning difficulties, attention deficit hyperactivity disorder (ADHD), and other cognitive and neurobehavioral deficits. Results from numerous studies suggest that dysfunction of the blood-brain barrier (BBB) structures is an important step in the neurotoxicity of cadmium. A rat-specific BBB marker protein, the endothelial barrier antigen (EBA), has been previously isolated and classified by Sternberger and others. The mouse IgG1 clone, anti-endothelial barrier antigen (anti-EBA), detects a protein triplet (23.5kDa, 25 kDa, and 30kDa) localized to the luminal surface of central and peripheral nervous system (CNS and PNS) vascular endothelial cells with selective permeability barrier functions. This marker has been widely used for characterizing BBB alterations under demyelinating, inflammatory, and other CNS pathologies. Many studies have been published using the rat model system for studying the neurotoxic effect of acute and chronic exposure to cadmium.We applied the indirect immunofluorescent techniques using the anti-EBA antibody in conjunction with the Olympus cellSens computerized image analysis to detect and quantify the surface areas of BBB-competent microvessel profiles in paraformaldehyde-fixed, paraffin-embedded brains of term-delivered young rats after intraperitoneal injection of a single dose of cadmium chloride. We detected a statistically significant reduction in EBA-positive microvessel surface areas in the forebrain (t = 5.86, df = 1789, p-value < 0.001) and cerebellum (t=73.40, df=1337, p < 0.001) of cadmium-treated rats compared to the normal controls. Thus, this study supports the hypothesis that the EBA is a sensitive and measurable indicator for quantitative assessment of the impact of cadmium exposure in the developing rat brain.

Оценка эффективности работы и перспектив развития санитарной авиации в условиях мегаполиса на примере г.Москвы

The objectives of the study are to develop a structural and functional model, principles and algorithms of organizational and methodological support of helicopter evacuation of patients to specialized medical organizations of megapolis; to evaluate their effectiveness analysing the results of treatment of patients with significant urgent pathology. Materials and research methods. The results of treatment of 241 patients with urgent pathology at the treatment facilities of the Moscow Health Department — City Clinical Hospital No.15 named after O.M. Filatov, S.S. Yudin State Clinical Hospital and N.S. Sklifosovskiy Research Institute of Emergency Medicine in 2016-2019 — were analyzed. Inclusion criteria: patients with bleeding (isolated or in combination with acute trauma) requiring surgical intervention; with acute coronary syndrome (unstable angina pectoris, myocardial infarction with and without ST-segment elevation); with vascular pathology of central nervous system or craniocerebral trauma, requiring emergency hospitalization of the patient in a specialized medical institution — provided that the time of delivery of all these patients to the hospital was at least 30 minutes from the time of call. Exclusion criteria: patients with mental illness, infectious-inflammatory processes, severe comorbid somatic diseases in decompensation stage (established by anamnesis, examination or autopsy reports); incurable cancer patients and any urgent patients whose delivery time to the specialized hospital was less than 30 minutes from the time of call. All patients included in the study were divided into 2 groups: The main — 1st group — included 112 patients delivered to the profile medical institution of the megapolis on a medical helicopter. The comparison group — 2nd group — consisted of 129 patients with similar urgent pathology, hospitalized to the specialized hospitals of the city by ground ambulance transport. Research results and their analysis. The analysis of the study results showed: – performance of air medical teams is comparable to or exceeds that of ground ambulance teams; – number of total bed-days in the group hospitalized by air ambulance was higher than in the comparison group; – inpatient outcomes and long-term outcomes were comparable in both groups; – pilot study of the use of mobile diagnostic ultrasound in providing emergency and urgent medical care allows us to consider this method as a promising one, but it requires further evidence accumulation. Thus, the performance of medical aviation is not inferior to the performance of ground ambulance teams, and in some aspects, even exceed them, which confirms the high potential of its use in megapolis conditions and in remote and hard-to-reach areas.

How childhood trauma and emotions influence essential tremor and its severity in Sakarya Province.

Essential tremor (ET) is among the most common central nervous system disorders. It is characterised by symmetrical and bilateral postural tremor, usually affecting the hands. Alongside such motor symptoms, psychiatric symptoms, such as anxiety and depression, often occur. This study aimed to investigate how anxiety, depression and childhood trauma influence ET patients' tremor frequency and severity. The participants comprised 85 patients and 70 control volunteers. Participating patients have been admitted to our clinic for hand tremor complaints and diagnosed with ET, according to the Washington Heights Inwood Genetic Study of Essential Tremor (WHIGET) diagnosis criteria, and they returned for follow-up for at least one year after their initial treatment. Patients with thyroid dysfunction, Parkinson's disease, central nervous system pathology, a history of smoking or alcohol use or a history of drug use that may cause tremor were excluded from the study. Patients' demographic data, such as their age and gender, age at disease onset, disease duration, family history and tremor severity were recorded. The Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI) and Childhood Trauma Questionnaire (CTQ) were applied to all patients. Statistically significant differences were found in BDI score averages and BAI score averages between the patient and control groups (p = 0.002; p = 0.001) and physical abuse, emotional neglect and sexual abuse scores on the CTQ scale (p = 0.001, p = 0.007 and p = 0.001, respectively). Childhood mental trauma and emotional mood disorders are more common among ET patients. However, these disorders do not appear to affect ET severity.

Drug Nanocrystals: Focus on Brain Delivery from Therapeutic to Diagnostic Applications.

The development of new drugs is often hindered by low solubility in water, a problem common to nearly 90% of natural and/or synthetic molecules in the discovery pipeline. Nanocrystalline drug technology involves the reduction in the bulk particle size down to the nanosize range, thus modifying its physico-chemical properties with beneficial effects on drug bioavailability. Nanocrystals (NCs) are carrier-free drug particles surrounded by a stabilizer and suspended in an aqueous medium. Due to high drug loading, NCs maintain a potent therapeutic concentration to produce desirable pharmacological action, particularly useful in the treatment of central nervous system (CNS) diseases. In addition to the therapeutic purpose, NC technology can be applied for diagnostic scope. This review aims to provide an overview of NC application by different administration routes, especially focusing on brain targeting, and with a particular attention to therapeutic and diagnostic fields. NC therapeutic applications are analyzed for the most common CNS pathologies (i.e., Parkinson’s disease, psychosis, Alzheimer’s disease, etc.). Recently, a growing interest has emerged from the use of colloidal fluorescent NCs for brain diagnostics. Therefore, the use of NCs in the imaging of brain vessels and tumor cells is also discussed. Finally, the clinical effectiveness of NCs is leading to an increasing number of FDA-approved products, among which the NCs approved for neurological disorders have increased.

Echoencephalography of encephalopathy due to congenital lymphocytic choriomeningitis virus.

AbstractCongenital lymphocytic choriomeningitis virus (LCMV) infection is a transient intrauterine viral infection with selective teratogenicity depending on the timing of the primary maternal infection. LCMV is cleared from the body of the fetus after the acute phase of illness and, in most cases, has lost its virulence at the time of birth. LCMV competes with extracellular matrix proteins for its tropism toward heavily glycosylated alpha‐dystroglycan. In the first trimester, while tropism toward heart myoblasts is high, intrauterine infection (IUI) can lead to miscarriage or fetal demise. Later in pregnancy, LCMV becomes neurotropic with tropism toward retina and brain. Most often systemic symptoms are subtle or absent at the time of birth. The timing of the IUI determines the neuroteratogenic phenotypes of congenital LCMV infection. IUI that occurs early during gestation can lead to isolated cerebellar dysgenesis and hypoplasia. When IUI occurs during neural radial migration, echoencephalography shows defective cerebral opercularization, intracranial calcifications at the gray‐white matter junction, enlarged extra‐axial subarachnoid space, and cortical dysplasia. When IUI occurs after the completion of insular opercularization (late second trimester), echoencephalography shows extensive cystic periventricular leukomalacia with bi‐occipital porencephaly and mild defects in gyrogenesis. A late gestation IUI induces aseptic LCMV meningitis with occlusion of the aqueduct of Sylvius, leading to congenital obstructive hydrocephalus. Congenital LCMV remains underdiagnosed as clinical manifestations are predominantly neurologic. As echoencephalography remains the preferred screening strategy for detecting neonatal central nervous system pathology, prior knowledge of echoencephalography of congenital LCMV may facilitate its recognition, prompting a serological evaluation.

Effects of a Fully Humanized Type II Anti-CD20 Monoclonal Antibody on Peripheral and CNS B Cells in a Transgenic Mouse Model of Multiple Sclerosis.

Successful therapy with anti-CD20 monoclonal antibodies (mAbs) has reinforced the key role of B cells in the immunopathology of multiple sclerosis (MS). This study aimed to determine the effects of a novel class of anti-CD20 mAbs on vascular and extravascular central nervous system (CNS)-infiltrating B cells in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Male hCD20xhIgR3 mice and wild-type C57BL/6 (B6) mice were immunized with human myelin oligodendrocyte glycoprotein (MOG)1–125 to induce EAE. While hCD20xhIgR3 mice were injected intravenously with an anti-human CD20 mAb (5 mg/kg) (rituximab (a type I anti-CD20 mAb) or obinutuzumab (a type II anti-CD20 mAb), B6 mice received the anti-mouse CD20 antibody 18B12. Neither mAb affected clinical disease or serum antibody levels. Obinutuzumab and rituximab had an impact on splenic and CNS-infiltrated B cells with slightly differential depletion efficacy. Additionally, obinutuzumab had beneficial effects on spinal cord myelination. B cell depletion rates in the 18B12/B6 model were comparable with those observed in obinutuzumab-treated hCD20xhIgR3 mice. Our results demonstrate the usefulness of anti-CD20 mAbs for the modulation of B cell-driven peripheral immune response and CNS pathology, with type II antibodies potentially being superior to type I in the depletion of tissue-infiltrating B cells.

513 Surveilling Cerebrospinal Fluid Protein Biomarkers in Brain Metastasis

INTRODUCTION: Cerebrospinal fluid (CSF) is in constant and direct contact with the brain parenchyma, vessels and meninges. The distribution and relative isolation of CSF makes it valuable in the evaluation of central nervous system pathologies. CSF protein profiling has been widely studied in neuro-degenerative and inflammatory diseases. This analysis may also be relevant in patients with brain metastases. METHODS: Patients were enrolled between May 2017 and March 2020 under an IRB protocol. CSF and plasma were processed and stored at -80°C. Concentrations of 142 soluble proteins were quantified by Luminex (Eve Technologies). RESULTS: Seventy-four patients were included in this study. Of the 60 patients with brain metastases, most had lung cancer (N=29), melanoma (N=10) and breast cancer (N=7). Non-malignant samples included normal pressure hydrocephalus (NPH, N=5), CSF leak (N=9) and radiation necrosis (N=9). Of the 142 soluble proteins profiled, 44 were significantly elevated in patients with LMD compared to intraparenchymal disease. None were more elevated in intraparenchymal disease. This finding was not replicated in the plasma. The CSF profile of patients with LMD and NPH were highly similar. CONCLUSION: Soluble CSF proteins are detectable in patients with brain metastases and concentrations differ based on extent of intracranial disease. This difference was not seen in plasma. These findings suggest that patients with LMD have a protein signature, different from those with intraparenchymal brain metastases only, which can help augment current diagnostic standards and reflect the tumor microenvironment. The similarity of LMD and NPH CSF proposes a similar pathogenesis and warrants further exploration. Further analysis of clinical data including survival and treatment response may assist in the management of patients with brain metastases.

Understanding the Blood-Brain Barrier and Beyond: Challenges and Opportunities for Novel CNS Therapeutics.

This review addresses questions on how to accomplish successful central nervous system (CNS) drug delivery (i.e., having the right concentration at the right CNS site, at the right time), by understanding the rate and extent of blood‐brain barrier (BBB) transport and intra‐CNS distribution in relation to CNS target site(s) exposure. To this end, we need to obtain and integrate quantitative and connected data on BBB using the Combinatory Mapping Approach that includes in vivo and ex vivo animal measurements, and the physiologically based comprehensive LEICNSPK3.0 mathematical model that can translate from animals to humans. For small molecules, slow diffusional BBB transport and active influx and efflux BBB transport determine the differences between plasma and CNS pharmacokinetics. Obviously, active efflux is important for limiting CNS drug delivery. Furthermore, liposomal formulations of small molecules may to a certain extent circumvent active influx and efflux at the BBB. Interestingly, for CNS pathologies, despite all reported disease associated BBB and CNS functional changes in animals and humans, integrative studies typically show a lack of changes on CNS drug delivery for the small molecules. In contrast, the understanding of the complex vesicle‐based BBB transport modes that are important for CNS delivery of large molecules is in progress, and their BBB transport seems to be significantly affected by CNS diseases. In conclusion, today, CNS drug delivery of small drugs can be well assessed and understood by integrative approaches, although there is still quite a long way to go to understand CNS drug delivery of large molecules.

2021 Workshop: Neurodegenerative Diseases in the Gut-Brain Axis—Parkinson's Disease

2021 Workshop: Neurodegenerative Diseases in the Gut-Brain Axis—Parkinson's Disease

Drug Design Targeting the Muscarinic Receptors and the Implications in Central Nervous System Disorders.

There is substantial evidence that cholinergic system function impairment plays a significant role in many central nervous system (CNS) disorders. During the past three decades, muscarinic receptors (mAChRs) have been implicated in various pathologies and have been prominent targets of drug-design efforts. However, due to the high sequence homology of the orthosteric binding site, many drug candidates resulted in limited clinical success. Although several advances in treating peripheral pathologies have been achieved, targeting CNS pathologies remains challenging for researchers. Nevertheless, significant progress has been made in recent years to develop functionally selective orthosteric and allosteric ligands targeting the mAChRs with limited side effect profiles. This review highlights past efforts and focuses on recent advances in drug design targeting these receptors for Alzheimer’s disease (AD), schizophrenia (SZ), and depression.

Polysynaptic reflex complexes in clinical neurology

The results of the study of spinobulbospinal reflex during 25 years in healthy people and in various nervous system diseases with affection of afferent and efferent systems, subcortical formations of brain and muscles (facial muscle contracture, miofascial pain syndrome) are given. It is shown that the inconstancy of many reflex characteristics (latency, amplitude, response duration, manifestation) is its basic property in normal conditions. In central nervous system pathology the stabilization of the m entioned parameters comes showing disorder of the program of formation and performance of motion.

Amplitude-Integrated Electroencephalography: A Primer for Neonatologists and Practitioners in the NICU.

Amplitude-integrated electroencephalography (aEEG) is an essential tool used in the NICU to monitor infants with central nervous system pathology and encephalopathy. This review provides a summary of aEEG, including clinical indications, interpretation of different tracing patterns, and seizure identification, which are essential skills for teams caring for sick newborns. We also discuss the limitations of the clinical application of aEEG in this population.

Bile acids attenuate PKM2 pathway activation in proinflammatory microglia

Glycolysis is the metabolic pathway that converts glucose into pyruvate. Central nervous system (CNS) pathologies, such as spinal cord injury (SCI) and ischemia, are accompanied by an increase of the glycolytic pathway in the damaged areas as part of the inflammatory response. Pyruvate kinase is a key glycolytic enzyme that converts phosphoenolpyruvate and ADP to pyruvate and ATP. The protein has two isoforms, PKM1 and PKM2, originated from the same gene. As a homodimer, PKM2 loses the pyruvate kinase activity and acts as a transcription factor that regulates the expression of target genes involved in glycolysis and inflammation. After SCI, resident microglia and hematogenous macrophages are key inducers of the inflammatory response with deleterious effects. Activation of the bile acid receptor TGR5 inhibits the pro-inflammatory NFκB pathway in microglia and macrophages. In the present study we have investigated whether bile acids affect the expression of glycolytic enzymes and their regulation by PKM2. Bacterial lipopolysaccharide (LPS) induced the expression of PKM1, PKM2 and its target genes in primary cultures of microglial and Raw264.7 macrophage cells. SCI caused an increase of PKM2 immunoreactivity in macrophages after SCI. Pretreatment with tauroursodeoxycholic acid (TUDCA) or taurolithocholic acid (TLCA) reduced the expression of PKM2 and its target genes in cell cultures. Similarly, after SCI, TUDCA treatment reduced the expression of PKM2 in the lesion center. These results confirm the importance of PKM2 in the inflammatory response in CNS pathologies and indicate a new mechanism of bile acids as regulators of PKM2 pathway.

Targeting the Meningeal Compartment to Resolve Chemobrain and Neuropathy via Nasal Delivery of Functionalized Mitochondria.

Cognitive deficits (chemobrain) and peripheral neuropathy occur in ∼75% of patients treated for cancer with chemotherapy and persist long-term in >30%of survivors. Without preventive or curative interventions and with increasing survivorship rates, the population debilitated by these neurotoxicities is rising. Platinum-based chemotherapeutics, including cisplatin, induce neuronal mitochondrial defects leading to chemobrain and neuropathic pain. This study investigates the capacity of nasally administered mesenchymal stem cell-derived mitochondria coated with dextran-triphenylphosphonium polymer (coated mitochondria) to reverse these neurotoxicities. Nasally administered coated mitochondria are rapidly detectable in macrophages in the brain meninges but do not reach the brain parenchyma. The coated mitochondria change expression of >2400genes regulating immune, neuronal, endocrine and vascular pathways in the meninges of mice treated with cisplatin. Nasal administration of coated mitochondria reverses cisplatin-induced cognitive deficits and resolves neuropathic pain at a >55-timeslower dose compared to uncoated mitochondria. Reversal of these neuropathologies is associated with resolution of cisplatin-induced deficits in myelination, synaptosomal mitochondrial integrity and neurogenesis. These findings demonstrate that nasally administered coated mitochondria promote resolution of chemobrain and peripheral neuropathy, thereby identifying a novel facile strategy for clinical application of mitochondrial donation and treating central and peripheral nervous system pathologies by targeting the brain meninges.

Neurocoagulation from a Mechanistic Point of View in the Central Nervous System.

Coagulation mechanisms are critical for maintaining homeostasis in the central nervous system (CNS). Thrombin, an important player of the coagulation cascade, activates protease activator receptors (PARs), members of the G-protein coupled receptor family. PAR1 is located on neurons and glia. Following thrombin activation, PAR1 signals through the extracellular signal-regulated kinase pathway, causing alterations in neuronal glutamate release and astrocytic morphological changes. Similarly, the anticoagulation factor activated protein C (aPC) can cleave PAR1, following interaction with the endothelial protein C receptor. Both thrombin and aPC are expressed on endothelial cells and pericytes in the blood-brain barrier (BBB). Thrombin-induced PAR1 activation increases cytosolic Ca2+ concentration in brain vessels, resulting in nitric oxide release and increasing F-actin stress fibers, damaging BBB integrity. aPC also induces PAR1 activation and preserves BBB vascular integrity via coupling to sphingosine 1 phosphate receptors. Thrombin-induced PAR1 overactivation and BBB disruption are evident in CNS pathologies. During epileptic seizures, BBB disruption promotes thrombin penetration. Thrombin induces PAR1 activation and potentiates N-methyl-D-aspartate receptors, inducing glutamate-mediated hyperexcitability. Specific PAR1 inhibition decreases status epilepticus severity in vivo. In stroke, the elevation of brain thrombin levels further compromises BBB integrity, with direct parenchymal damage, while systemic factor Xa inhibition improves neurological outcomes. In multiple sclerosis (MS), brain thrombin inhibitory capacity correlates with clinical presentation. Both thrombin inhibition by hirudin and the use of recombinant aPC improve disease severity in an MS animal model. This review presents the mechanisms underlying the effects of coagulation on the physiology and pathophysiology of the CNS.

Knockdown of circ_0007290 alleviates oxygen-glucose deprivation-induced neuronal injury by regulating miR-496/PDCD4 axis

Circular RNAs (circRNAs) are highly enriched in the brain and involved in many types of central nervous system pathologies. Herein, this study aimed to investigate the role and mechanism of circ_0007290 in ischemic stroke.The oxygen-glucose deprivation (OGD) model was established with the HCN-2 cells in vitro. Levels of genes and proteins was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. In vitro experiments were conducted using cell counting kit-8 (CCK-8) assay, EdU (5-ethynyl-2'-deoxyuridine) assay, flow cytometry and ELISA, respectively. The levels of lactate dehydrogenase (LDH) were measured using the commercial kit. RNA pull-down and dual-luciferase reporter assay were used to identify the target relationship between miR-496 and circ_0007290 or PDCD4 (programmed cell death protein 4).Circ_0007290 expression was elevated in acute ischemic stroke (AIS) patients and OGD-induced cell injury model. OGD stimulation induced neuronal apoptosis, promoted LDH release, and enhanced inflammation in HCN-2 cells, which all were reversed by the knockdown of circ_0007290. Mechanistically, circ_0007290 served as a sponge for miR-496 to relieve the repression of miR-496 on the expression of its target PDCD4. Moreover, miR-496 inhibition or PDCD4 overexpression abolished the inhibitory effects of circ_0007290 knockdown OGD-evoked neuronal injury.Knockdown of circ_0007290 alleviated OGD-induced neuronal injury by regulating miR-496/PDCD4 axis, providing a novel insight into the pathology of ischemic stroke.

MAC2 is a long-lasting marker of peripheral cell infiltrates into the mouse CNS after bone marrow transplantation and coronavirus infection.

Microglia are the primary resident myeloid cells of the brain responsible for maintaining homeostasis and protecting the central nervous system (CNS) from damage and infection. Monocytes and monocyte-derived macrophages arising from the periphery have also been implicated in CNS pathologies, however, distinguishing between different myeloid cell populations in the CNS has been difficult. Here, we set out to develop a reliable histological marker that can assess distinct myeloid cell heterogeneity and functional contributions, particularly in the context of disease and/or neuroinflammation. scRNAseq from brains of mice infected with the neurotropic JHM strain of the mouse hepatitis virus (JHMV), a mouse coronavirus, revealed that Lgals3 is highly upregulated in monocyte and macrophage populations, but not in microglia. Subsequent immunostaining for galectin-3 (encoded by Lgals3), also referred to as MAC2, highlighted the high expression levels of MAC2 protein in infiltrating myeloid cells in JHMV-infected and bone marrow (BM) chimeric mice, in stark contrast to microglia, which expressed little to no staining in these models. Expression of MAC2 was found even 6-10months following BM-derived cell infiltration into the CNS. We also demonstrate that MAC2 is not a specific label for plaque-associated microglia in the 5xFAD mouse model, but only appears in a distinct subset of these cells in the presence of JHMV infection or during aging. Our data suggest that MAC2 can serve as a reliable and long-lasting histological marker for monocyte/macrophages in the brain, identifying an accessible approach to distinguishing resident microglia from infiltrating cells in the CNS under certain conditions.

The visual consequences of virtual school: acute eye symptoms in healthy children

To investigate acute eye symptoms in healthy children after a typical day of virtual school during the COVID-19 pandemic. The study population included 110 healthy children 10-17 years of age who were enrolled in full-time or hybrid virtual school. Children with a history of central nervous system or ocular pathology, recent concussions, reported poor vision, convergence insufficiency, history of orthoptic therapy, strabismus, amblyopia, or learning disorders were excluded. Background information was collected, including demographics, family and personal ocular history, and virtual school specifications. Eligible children completed a modified convergence insufficiency symptom survey (CISS) and an asthenopia survey before and after a virtual school session. CISS and asthenopia survey symptoms were scored, and the differences in symptomatology before and after school were calculated. The average sum of the CISS scores increased from 5.17 before school to 9.82 after (P < 0.001), with 61% of children recording an increase in convergence insufficiency symptoms and 17% experiencing severe convergence insufficiency symptoms after school. Average asthenopia symptom scores increased from 1.58 to 2.74 (P < 0.001), with 53% of children recording an increase in asthenopia symptoms. Significant increases were seen in 12 of 15 CISS questions and in 4 of 5 asthenopia questions. In this study cohort, otherwise healthy children experienced acute ocular symptoms following virtual school.

Early life stress-induced neuroinflammation and neurological disorders: a novel perspective for research.

Early life stress-induced neuroinflammation and neurological disorders: a novel perspective for research.

Childhood Hypertension: An Observational Study from a Tertiary Care Centre, Gujarat, India

Introduction: Childhood hypertension is an underestimated problem in India and other developing countries. It often leads to Hypertension in adult. Hypertensive children, although usually asymptomatic, already manifest evidence of target organ damage. Many of hypertensive children have left ventricular hypertrophy and increased carotid intima-media thickness, a marker of early atherosclerosis. Hypertensive children are very prone to develop target organ damage like retinopathy, renal damage, cardiac complications if remains undiagnosed and untreated for long. Other risk factors like cardiovascular disease, diabetes mellitus and hyperlipidaemia must also be looked for in hypertensive children. Aim: To study the prevalence, clinical profile, aetiology and to analyse various management protocol, complications, and early outcomes of hypertension in hospitalised children aged between 5-10 years. Materials and Methods: This was a prospective, observational analytical study conducted in the Department of Paediatrics of a Tertiary Care Centre at Ahmedabad, Gujarat, India, from 1st October 2017 to 30th September 2019. Blood pressure was measured by mercury sphygmomanometer using auscultatory method in all admitted patients in Paediatrics Department between the age of 5-10 years as a part of vital monitoring. A total of 103 patients having average systolic blood pressure and/or diastolic blood pressure greater than or equal to 95th percentile for that age, sex and height on three or more occasions were included in the study and their comprehensive details were recorded in prestructured proforma. The outcome was recorded as data in excel sheet and arranged in tables. Results: The prevalence of hypertension was 0.96%. The mean age of the study population was 8 years, and the male:female ratio was 1.09:1. Vomiting was the most common presenting complaint followed by fever and puffiness of eyes. A higher incidence of fever on presentation was due to the associated infective pathology of Central Nervous System (CNS). Pallor was the most common finding on general examination. Neurological deficit was observed in patients with hypertensive encephalopathy and stroke. Overall, 21 (20.38%) patients were in stage 2 hypertension, amounting to hypertensive emergencies, 48 (46.6%) patients with hypertension had an underlying renal disorder, followed by CNS disorder in 47 (45.6%). Amlodipine (26.21%) was the most common drug used in hypertensive patients. Most common complication of the present study was hypertensive retinopathy seen in 14 patients (13.59%). Conclusion: In hospitalised patients, the prevalence of hypertension was 0.96% with a male preponderance. On admission, the most prevalent complaints were vomiting and fever; pallor and puffiness of eyes were the most common general examination findings, and ascites was the most common systemic examination result. The most common secondary cause of hypertension was renal disease, with acute glomerulonephritis as most prevalent