The disorder of the iron metabolism as a possible mechanism for the development of neurodegeneration after new coronavirus infection of SARS-CoV-2

The involvement of the nervous system in the pathological process that occurs when COVID-19 is infected is becoming more and more obvious. The question of the possibility of the debut or progression of the already developed Parkinsonism syndrome in patients who have undergone COVID-19 is regularly raised. A large number of hypotheses are put forward to explain this relationship. It is assumed that a violation of iron metabolism in the brain may underlie the development and progression of neurodegenerative diseases, including after the new coronavirus infection SARS-CoV-2. The analysis of stu dies on the possible influence of iron metabolism disorders on the occurrence and mechanism of development of neurodegenerative diseases after infection with SARS-CoV-2 has been carried out. The processes of physiological maintenance of iron homeostasis, as well as the influence of physiological aging on the accumulation of iron in the central nervous system are described. The relationship between hyperferritinemia occurring in COVID-19 and ferroptosis as the basis of the neurodegenerative process in Parkinsons disease and Alzheimers disease is discussed. The main molecular mechanisms involved in ferroptosis are described. Examples of involvement of metal homeostasis disorders in the process of altering the structure of -synuclein, synthesis of -amyloid, hyperphosphorylated tau- protein are given. The causes of excessive iron accumulation in certain brain structures are discussed. The question of the possibility of using the assessment of changes in iron metabolism as a new biomarker of the progression of Parkinsons disease is analyzed. (1 figure, bibliography: 62 refs)

The incidence and pathophysiology of neurological symptoms in COVID-19

The central nervous system seems to be quite vulnerable to SARS-CoV-2, leading to a variety of alteration pathways, high incidence and variability of the neurological symptoms of COVID-19. The COVID-19 symptoms, possibly associated with alteration to the central nervous system, include hyperthermia, shortness of breath, fatigue, headache, dizziness, dysphonia, dysphagia, hyposmia and anosmia, hypogeusia and ageusia, impairment of consciousness. The impairment of olfaction and gustation are the most common symptoms of the nervous system alteration (98% and 70%, respectively), which is most likely a consequence of the alteration of the receptors. Presumably the pathogenesis of dysphonia and dysphagia may involve neurodegenerative mechanisms or may be associated with a predominantly demyelinating alteration of the caudal cranial nerves. Pathomorphological findings in the brain of the COVID-19 patients include diffuse hypoxic and focal ischemic injuries of various sizes up to ischemic infarctions (in thrombosis of large arteries); microangiopathy; vasculitis; diapedetic and confluent hemorrhages with possible progression to hemorrhagic infarctions and rarely intracerebral hematomas. Acute cerebrovascular accident worsens the course of COVID-19 and can worsen the clinical outcome, taking into account the mechanisms of the central nervous system alteration in highly contagious coronavirus infections (SARS-CoV, MERS, SARS-CoV-2), including embolism, hypoxia, neurodegeneration, systemic inflammatory response and immune-mediated alteartion to the nervous tissue. A fairly rare complication of coronavirus infection, however, acute myelitis requires attention due to the severity of neurological disorders. The literature data show high incidence and polymorphism of the symptoms of the central nervous system alteration, as well as the important role of the cerebrovascular and neurodegenerative pathogenesis of brain alteration in COVID-19, which is taken into account in examining and treating the patients with new coronavirus infection. (1 figure, bibliography: 61 refs)

The history of the research of neuroinfections in the Department of Nervous Diseases of the Imperial Medical Surgical (Military Medical) Academy

The article presents the history of the research of neuroinfections at the Nervous Diseases Department of the Imperial Medical Surgical Academy, later the Military Medical Academy, from 1860 until nowadays. One of the outstanding achievements of Russian and world medicine in the twentieth century, constituting an entire era in neurology and virology, was the comprehensive study of tick-borne encephalitis by Aleksandr Gavrilovich Panov. He made a huge contribution to the research of this infection: Clinic of spring-summer encephalitis (1938) the first journal article in the world literature on the clinical aspects of tick-borne encephalitis; the first Ph.D. thesis on the clinical picture of tick-borne encephalitis was successfully defended by A.G. Panov on February 20, 1939 under the leadership of A.V. Triumfov; the first monograph on tick-borne encephalitis and other encephalitis Seasonal summer encephalitis (Vladivostok, 1940) also belongs to A.G. Panov. The results of the research of tick-borne encephalitis in 19341949 became the subject of a doctoral dissertation, defended on December 8, 1951. In 1956, the classic monograph by A.G. Panov Tick-borne encephalitis was published. At the end of XX and beginning of XXI centuries research work in the field of neuroinfection expanded, studies were carried out in various directions, including neuropathology of herpesvirus, alteration of the nervous system in botulism, acute demyelinating polyneuropathies, neuropathology of chlamydial infection, neuroborreliosis, neuropathology of infective endocarditis, alteration of the blood-brain barrier in meningitis, treatment of neuroinfectious diseases. For more than a century and a half, the staff of the Department of Nervous Diseases of the Imperial Medical Surgical (Military Medical) Academy have created and laid the foundation for the doctrine of neuroinfections for numerous followers, as well as the modern generation of neurologists and doctors of related specialties (bibliography: 10 refs)

Comparative diagnostic sensitivity of the substantia nigra transcranial sonography and salivary gland biopsy in patients with Parkinson’s disease

Parkinsons disease is a chronic neurodegenerative disease, the diagnosis of which remains challenging at the early stages, although clinical diagnostic criteria are developed. The diagnostic accuracy is only 58% for patients at early Parkinsons disease stages. The sensitivity and specificity of transcranial sonography of the substantia nigra used for Parkinsons disease verification is about 85% and 71%, respectively. It has been shown that the aggregates of -synuclein in the nerve fibers in major salivary glands may be seen in Parkinsons disease patients. The availability of the salivary glands for morphological study made it possible to investigate the approaches of the in vivo histological diagnosis of Parkinsons disease based on the detection of -synuclein aggregates in the nerve fibers innervating the glands. Aim: To evaluate and compare the sensitivity of transcranial sonography of the substantia nigra and sublingual salivary gland biopsy. Materials and methods: Six patients with clinically verified Parkinsons disease were enrolled. Evaluation of the neurological state using special scales, transcranial sonography of the substantia nigra and sublingual salivary gland biopsy was performed. Results: Mean age of patients was 59 [58; 60.7] years, mean disease duration period was 5 [3; 7.75] years and the mean HoehnYahr stage was 2.25 [2; 2.5]. Hyperechogenicity of the substantia nigra was found in 3 of 6 patients and the substantia nigra sensitivity was shown to be 50%. Sublingual salivary gland biopsy was positive for -synuclein in 6 of 6 patients and the sensitivity of method was shown to be 100%. No adverse events after biopsy were registered. Conclusion: The sensitivity of sublingual salivary gland biopsy was higher than those of transcranial sonography of the substantia nigra, which indicates the prospect of using the biopsy method as a more sensitive diagnostic tool in Parkinsons disease (1 table, bibliography: 19 refs)

Guillain-Barré syndrome: diagnosis and treatment guidelines

GuillainBarr syndrome is an acute, rapidly progressive immune-mediated disease of the peripheral nervous system, combining several variants and subtypes with various clinical, pathophysiological and electrophysiological signs. GuillainBarr syndrome usually develops 13 weeks after the viral or bacterial infection, which acts as the trigger triggering autoimmune mechanisms, leading to demyelination and axonal damage. The disease is getting more acute due to the emergence of a new coronavirus infection. Behind the diseases dipathophysiology there is the activation of cellular and humoral immunity with the production of autoantibodies to specific gangliosides and glycolipids and the formation of circulating immune complexes that attack peripheral nerves and roots (the phenomenon of molecular mimicry). The examination of patients requires an integrated approach, including, along with clinical and anamnestic data, the results of laboratory and neurophysiological examination. The treatment of patients with GuillainBarr syndrome is carried out in an intensive care unit and includes both pathogenetic therapy and nonspecific measures aimed to correct dysfunctions of vital organs, prevent complications and provide symptomatic therapy. Currently, the main direction of pathogenetic therapy of this disease is the use of high-dose intravenous immunotherapy with human normal immunoglobulin preparations or high-volume therapeutic plasmapheresis. Taking into account the absence of data about differences in the effectiveness of these methods, the choice of direction is determined taking into account the contraindications and possible development of adverse events, as well as the capabilities of the medical institution (2 tables, bibliography: 15 refs)

The structure and risk factors of the postoperative cerebral dysfunction in oncosurgery

Aim of the research was to study the features of the structure of postoperative cerebral dysfunction, establishing the risk factors for the development of postoperative cerebral dysfunction and for the each of the clinical types during operations for malignant neoplasms of the chest and abdomen. The study was conducted in 2 stages: a retrospective study based on medical records and a prospective study. In a retrospective study by the method of directed selection from 93,129 clinical cases of patients, 47 cases of patients with acute stroke after surgery were selected. In prospective study, 102 patients (69 men, 33 women) aged 38 to 85 years were examined, the median age was 67 years. They were divided into two study groups: thoracic, abdominal. In a retrospective study, the incidence of perioperative stroke was 0.05%. In a prospective study of surgical operations for malignant neoplasms of the chest and abdomen, the incidence of postoperative cerebral dysfunction was 34%, perioperative stroke 2%, symptomatic delirium of the early postoperative period 11%, deferred cognitive impairment 31%. Statistical processing of the prospective study data revealed 10 risk factors for postoperative cerebral dysfunction, 12 risk factors for perioperative stroke, 7 risk factors for symptomatic delirium of the early postoperative period, and 6 risk factors for deferred cognitive impairment. For each of the clinical types of postoperative cerebral dysfunction the Charlson comorbidity index has a significant predictive value, and therefore it seems appropriate to include this parameter in the preoperative examination algorithm (3 tables, bibliography: 8 refs)

Epileptic status: reality 2021

Epileptic status is one of the urgent conditions in neurology that requires clear and urgent measures at any stage of medical care. It ranks second among all urgent neurological conditions. The therapeutic principle time-brain is applicable not only for urgent measures in acute cerebrovascular accident, but also for the relief of epileptic status, since the worst prognosis is associated with an increase in the duration of seizure activity. According to the standards proposed in the world for the treatment of epileptic status, benzodiazepines, intravenous forms of antiepileptic drugs, and general anesthetics are used. In the Russian Federation, the use of many drugs is limited due to the lack of registration, their lack in standards, and unavailability in hospitals. Due to the lack of studies on the treatment of epileptic status that go beyond the early stage of status, most of the recommendations presented worldwide remain based on case series or expert judgment. The efficacy benefits of anti-status drugs used in the second and third stages of epileptic status therapy remain unclear. Therefore, if there is a choice of anti-status drugs, the decision of which drug, in what dose and in what sequence will be used, should be made by the senior and most trained doctor in this matter, taking into account the characteristics of each patient. Based on modern international and personal experience, the paper presents a step-by-step protocol for the treatment of generalized convulsive epileptic status, discusses the successes and problems of providing care to patients with this pathology in Russia. The quality of medical care in epileptic status can be significantly improved provided that medical personnel at all stages of the treatment protocol are required to evacuate patients with epileptic status to specialized centers of multidisciplinary hospitals with the possibility of examination and therapy, including the availability of EEG monitors, neuroimaging and laboratory capabilities, and also access to modern antiepileptic drugs (1 table, bibliography: 30 refs)

COVID-19-associated stroke: experience of Regional clinical hospital Krasnoyarsk city

Mechanisms of the impact of the new coronavirus infection on nervous system that leads to various neurological complications, including strokes, and disease patterns and prognosis for stroke patients with COVID-19 are actively discussed in the literature. The aim of the research was a comparison of clinical outcomes in stroke patients with SARS-CoV-2 infection and without. Random sampling of patients with stroke and laboratory-confirmed coronavirus infection SARS-CoV-2 (50 patients) was analyzed retrospectively. The control group consisted of 49 patients with stroke who did not have COVID-19. Patients in both groups were comparable by age, sex, rate of variation and type of stroke, localization of stroke and rating on the Rankin scale before the disease. The results showed that diabetes mellitus significantly more often (more than twice) occurred in stroke patients with COVID-19 (16%) in comparison with the control (7%). Atherosclerosis of brachiocephalic arteries prevailed in acute stroke patients without COVID-19 (88%). The mortality rate in acute stroke patients with COVID-19 was higher (22%) than among those without this infection (6%). At the same time, patients without a combination with COVID-19 had more severe disability on the Rankin scale three points (moderate disability) while patients with COVID-19 were discharged with two points on the Rankin scale (slight disability). Probably, this is since SARS-CoV-2 infection more often led to the lethal oucome in patients with more severe stroke and the survived patients were less disabled. Probably in increased samples these differences will be reversed. Thus, this research confirmed data that the association of stroke and COVID-19 significantly worsens clinical outcomes of stroke (2 tables, bibliography: 10 refs)

Clinical and pathogenetic aspects of acute pancreatic encephalopathy

Pancreatic encephalopathy is a formidable complication of acute pancreatitis, significantly aggravating the course and increasing the mortality rate in this disease. For pancreatic encephalopathy, an acute onset and fluctuating course with subsequent cyclic progression are typical, and the severity of neurological symptoms may be directly dependent on the activity of the pancreatic process. The risk of having residual symptoms, primarily in the form of cognitive impairment, increases with repeated episodes of acute pancreatic encephalopathy. In the pathogenesis of pancreatic encephalopathy, an important role is played by a combination of enzymatic and hormonal dysfunction of the pancreas, systemic microcirculation disorders due to hypovolemia, typical for acute pancreatitis, and changes in glucose metabolism associated with the effects of secondary hepatocellular insufficiency and pancreonecrosis. Microscopically, gross changes in the vascular link are revealed in the form of plasmorrhages and diapedesic hemorrhages in the Virchow-Robin spaces and the white matter of the brain, desquamation and dystrophy of endothelial cells, swelling of the adventitia membrane, sludge of blood corpuscles, plasma impregnation and segmental necrosis of the vascular wall with predominant involvement and small caliber. The presence of pancreatic encephalopathy should be suspected if neurological symptoms are detected in patients with symptoms of acute pancreatitis, such as psychomotor agitation, visual and auditory hallucinations, delirium, followed by episodes of deafness, adynamia, drowsiness, up to a state of catatonia and coma. In most cases, psychomotor agitation is combined with manifestations of the syndrome of irritation of the meninges. Focal neurological symptoms, myoclonia, hyperkinesis may be associated with mental and general cerebral symptoms. Mortality in acute pancreatic encephalopathy is due to shock, hemorrhagic complications, ketoacidosis, fatty embolism of cerebral vessels or renal failure (bibliography: 35 refs)

Interrelation of cognitive functions and neural networks with blood flow velocity through the internal jugular vein in patients with chronic cerebral ischemia

Understanding age-related and functional changes in cerebral venous circulation is critical for the development of new preventive, diagnostic and therapeutic approaches to maintaining brain health in the elderly. Chronic cerebral ischemia is one of the widespread socially significant vascular diseases caused by a decrease in the level of blood circulation. To assess the role of venous outflow through the internal jugular veins in cognitive decline and neural networks in patients with chronic cerebral ischemia, 30 men and 40 women (average age 66.5 years), cognitive functions and organization of neural networks were studied at high and low levels of cerebral venous blood flow through the internal jugular veins. To assess the venous outflow, the systolic blood flow rate was measured by the internal jugular veins. A higher rate of venous outflow through internal jugular veins is associated with a more successful performance of the Luria test for verbal memory. A higher or lower blood flow rate affects the formation of neural networks of the brain. At a higher blood flow rate, the predominant areas of the resting neural networks (the passive mode network of the brain and the salient network) are localized in the frontal regions, at a low blood flow rate, the predominant neural network (frontal-parietal) is located in the left hemisphere. The state of faster and slower venous outflow forms neural networks using different neural formations that affect verbal memory. Reorganization of neural networks in this case, apparently, is the central mechanism responsible for cognitive decline in chronic cerebral ischemia (2 figs, 1 table, bibliography: 10 refs)