Neuroinvasion and neurological complications in COVID-19

Neurological Symptoms ◽

Nausea And Vomiting ◽

Musculoskeletal Symptoms ◽

Control Group ◽

Consciousness Disorders ◽

Background. Coronavirus disease (COVID-19) affects not only the alveoli but also the central nervous system. The pathogenesis of neurological complications of COVID-19 is based on the receptor damage, cytokine-mediated injury, damage of the nervous system due to hypoxia, and neuronal damage due to the retrograde transport of the virus through nerve fibers. Objective. To determine the mechanisms of coronavirus neuroinvasion and treatment of neurological complications COVID-19. Materials and methods. Analysis of literature sources and own research on this topic. Results and discussion. In 3 days after infection viral antigens are detected in the olfactory sensory neurons of the nasal cavity epithelium, which confirms the transnasal invasion of coronaviruses. According to various authors, 36.4-84 % of patients with COVID-19 have neurological manifestations. In general, neurological symptoms of COVID-19 can be divided into three categories: symptoms of the central nervous system disorders (headache, dizziness, consciousness disorders, nausea and vomiting, ataxia, acute cerebrovascular disease, and epilepsy), symptoms of the peripheral nervous system disorders (hypogeusia, hyposmia, hypopsia, and neuralgia) and musculoskeletal symptoms. As viral infections cause cytokine storm, inflammation and hyperactive oxidation, it is advisable to use antioxidants in their treatment. According to the Japanese clinical guidelines for the treatment of acute respiratory distress syndrome, edaravone may be used as a free radical scavenger in such patients. In the experiment, edaravone reduced the area of infarction and promoted functional recovery in cerebral thrombosis. Other properties of edaravone include the prevention of excessive permeability of the pulmonary vessels’ endothelium. Own research has shown that edaravone (Ksavron, “Yuria-Pharm”) reduces the severity of inflammation and mortality in patients with COVID-19. In the control group, the level of the proinflammatory mediator interleukin-6 exceeded the upper limit of normal values by 1652.40 %, and in the Ksavron group – only by 269.97 %. Mortality in the control group was 14.3 %, and in the Ksavron group – 0 %. Conclusions. 1. Coronaviruses affect not only the lungs but also the nervous system. 2. Neurological symptoms of COVID-19 include headache, dizziness, consciousness disorders, nausea and vomiting, ataxia, acute cerebrovascular disease, hypogeusia, hyposmia, hypopsia, neuralgia, and musculoskeletal symptoms. 3. Edaravone (Ksavron) reduces the severity of inflammation and has an antioxidant effect, which justifies its use in COVID-19.

Neurological manifestations of COVID-19 – an approach to categories of pathology

Neurological Research and Practice ◽

10.1186/s42466-021-00138-9 ◽

2021 ◽

Vol 3 (1) ◽

Author(s):

Yana Leven ◽

Julian Bösel

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Cerebrovascular Disease ◽

Literature Search ◽

Case Series ◽

Neurological Symptoms ◽

Comparable Data ◽

Neurological Manifestations ◽

Case Definitions ◽

Abstract Background Various neurological manifestations of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported, associated with a broad spectrum of diverse neurological symptoms and syndromes. Estimating rate and relevance of these manifestations remains difficult as there is a lack of standardised case definitions. Methods We defined comprehensive categories including most reported neurological manifestations associated with SARS-CoV-2 to allow for a more standardised data collection. After a literature search of MEDLINE with ten keywords, 12 selected studies and larger case series were included. We compared the rate and relevance of neurological manifestations in hospitalized patients. We propose four main categories including 1) cerebrovascular disease, 2) inflammatory syndromes of the central nervous system (CNS), peripheral nervous system (PNS) and muscle, 3) metabolic/toxic dysfunction of CNS, PNS and muscle and 4) miscellaneous disorders. Conclusion Ageusia (702) and anosmia (805) have been reported as the most common and the first occurring neurological symptoms. Cerebrovascular disease (451) and encephalopathy (663) were associated with a more severe course and worse clinical outcome. Any neurological manifestation was associated with a longer hospital stay and a higher morbidity and mortality compared to patients without neurological manifestations. We suggest reporting future neurological manifestations of coronavirus disease-19 (COVID-19) following a pathophysiology-based approach using standardized pre-defined case definitions to yield more specific and comparable data.

An Investigation of the Effects of Curcumin on the Changes in the Central Nervous System of Rats Exposed to Aroclor 1254 in the Prenatal Period

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527317666180315170146 ◽

2018 ◽

Vol 17 (2) ◽

pp. 132-143 ◽

Cited By ~ 1

Author(s):

Mehmet Eray Alcigir ◽

Halef Okan Dogan ◽

Begum Yurdakok Dikmen ◽

Kubra Dogan ◽

Sevil Atalay Vural ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Neuron Specific Enolase ◽

Control Group ◽

Albino Rats ◽

Prenatal Period ◽

Aroclor 1254 ◽

Rat Pups ◽

Tunel Reaction ◽

Background & Objective: Aroclor 1254 is a widespread toxic compound of Polychlorinated Biphenyls (PCBs), which can create significant nervous problems. No remedies have been found to date. The aim of this study was to reveal the damage that occurs in the central nervous system of rat pups exposed to Aroclor 1254 in the prenatal period and to show the inhibiting effect of curcumin, which is a strong anti-oxidant and neuroprotective substance. Method: The study established 3 groups of adult female and male Wistar albino rats. The rats were mated within these groups and the offspring rats were evaluated within the group given Aroclor 1254 only (n=10) and the group was given both Aroclor 1254 and curcumin (n=10) and the control group (n=10). The groups were compared in respect of pathomorphological damage. The immunohistochemical evaluation was made of 8-hydroxdeoxyguanosine (8-OHdG), 4-hydroxynoneal (4HNE), myelin basic protein (MBP) expressions and TUNEL reaction. The biochemical evaluation was made of the changes in the TAS-TOS and Neuron Specific Enolase (NSE) levels. Damage was seen to have been reduced with curcumin in the 8OHdG and TUNEL reactions, especially in the forebrain and the midbrain, although the dosage applied did not significantly change TAS and TOS levels. Consequently, it was understood that Aroclor 1254 caused damage in the central nervous system of the pup in the prenatal period, and curcumin reduced these negative effects, particularly in the forebrain and the midbrain. Conclusion: It was concluded that curcumin could be a potential neuroprotective agent and would be more effective at higher doses.

Modern Views Concerning the Mechanisms of Blast Wave Influence on the Central Nervous System and Formation of Neurological Symptoms

INTERNATIONAL NEUROLOGICAL JOURNAL ◽

10.22141/2224-0713.6.84.2016.83129 ◽

2016 ◽

Vol 0 (6.84) ◽

pp. 139-142

Author(s):

V.А. Коrshnyak ◽

B.А. Nаsibullin

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Blast Wave ◽

Neurological Symptoms ◽

Effects of Electroacupuncture on Pain Threshold of Laboring Rats and the Expression of Norepinephrine Transporter andα2 Adrenergic Receptor in the Central Nervous System

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/9068257 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8

Author(s):

Qianli Tang ◽

Qiuyan Jiang ◽

Suren R. Sooranna ◽

Shike Lin ◽

Yuanyuan Feng ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Adrenergic Receptor ◽

Pain Threshold ◽

Norepinephrine Transporter ◽

Control Group ◽

Tail Flick ◽

Pregnant Rats ◽

Tail Flick Test ◽

To observe the effects of electroacupuncture on pain threshold of laboring rats and the expression of norepinephrine transporter andα2 adrenergic receptor in the central nervous system to determine the mechanism of the analgesic effect of labor. 120 pregnant rats were divided into 6 groups: a control group, 4 electroacupuncture groups, and a meperidine group. After interventions, the warm water tail-flick test was used to observe pain threshold. NE levels in serum, NET, andα2AR mRNA and protein expression levels in the central nervous system were measured. No difference in pain threshold was observed between the 6 groups before intervention. After intervention, increased pain thresholds were observed in all groups except the control group with a higher threshold seen in the electroacupuncture groups. Serum NE levels decreased in the electroacupuncture and MP groups. Increases in NET andα2AR expression in the cerebral cortex and decreases in enlarged segments of the spinal cord were seen. Acupuncture increases uptake of NE via cerebral NET and decreases its uptake by spinal NET. The levels ofα2AR are also increased and decreased, respectively, in both tissues. This results in a decrease in systemic NE levels and may be the mechanism for its analgesic effects.

Anti-programmed cell death-1 (PD-1) monoclonal antibodies involve reversible cranial dura matter

Oxford Medical Case Reports ◽

10.1093/omcr/omab077 ◽

2021 ◽

Vol 2021 (9) ◽

Author(s):

Hiroshi Kataoka ◽

Daisuke Shimada ◽

Hitoki Nanaura ◽

Kazuma Sugie

Keyword(s):

Central Nervous System ◽

Cell Death ◽

Nervous System ◽

Monoclonal Antibodies ◽

Programmed Cell Death ◽

Adverse Effects ◽

Neuromuscular Disorders ◽

Programmed Cell Death 1 ◽

ABSTRACT This case is the first document to describe a patient receiving anti-programmed cell death 1 (PD-1) antibodies which showed cranial dura matter involvement. According to the increasing use of anti-PD-1 monoclonal antibodies, adverse effects can occur in several organs since its ligand PD-L1 and PD-L2 are expressed in a wide variety of tissues. The estimated rate of neurological complications is 1–4.2% of patients, and neuromuscular disorders are the most common. Adverse effects on the central nervous system including encephalitis are less frequent. Here, a patient receiving anti-PD-1 antibodies showed cranial dura matter involvement, and the dura enhancement on MRI was resolved by withdrawal of the treatment with anti-PD-1 antibodies only.

Analysis of electrogenesis’ changes in mental retardation persons by using computer electroencephalography

Journal of Education, Health and Sport ◽

10.12775/jehs.2021.11.11.025 ◽

2021 ◽

Vol 11 (11) ◽

pp. 249-265

Author(s):

B. Lobasyuk ◽

L. Bartsevich ◽

A. Zamkovaya

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Mental Retardation ◽

Theta Rhythm ◽

Cognitive Activity ◽

Control Group ◽

Bioelectrical Activity ◽

Beta Rhythms ◽

The Brain

Justification. Mental retardation is a persistent decrease in human cognitive activity against the background of organic damage to the central nervous system. Neurophysiological diagnostics, in particular electroencephalography (EEG), most adequately reflects the morpho-functional state of the central nervous system, which is the basis of the mechanisms of mental activity, and the originality of the bioelectrical activity of the brain can be considered as the main indicator that determines a decrease in the level of intellectual development and, thereby, characterizes this state. This provision actualizes the search for highly informative indicators of the originality of the bioelectrical activity of the brain in children with intellectual disabilities. Purspose. With the use of periodometric analysis investigate EEG’s indicators and interhemispheric asymmetry of rhythms amplitudes in MR patients. Materials and methods. The EEG was recorded in a state of calm wakefulness with closed eyes with Neuron-Spectrum-2 electroencephalograph. Differences in indicators were tracked using the calculation of the coefficient of compliance (CC), EEG functional asymmetry coefficients in amplitude were determined, too. Results. It was revealed that in MR patients the amplitudes of the rhythms were greater than in healthy subjects. The greatest increase was determined in theta rhythm in the anterior temporal and posterior temporal leads in the left hemispheres. Duration indices in the delta, theta and alpha ranges of the EEG in mental retardation compared with the control group were increased, and the indices of the duration of beta rhythms - decreased. When analyzing FMPA in MR persons it turned out that in right-handers the negativeness of FMPA indices increased, and in left-handers there was an increase in the positivity of FMPA indices. Conclusions 1. With mental retardation, the amplitudes of the rhythms were greater than in healthy people. The greatest increase was determined in theta rhythm in the anterior temporal and posterior temporal leads in the left hemispheres. 2. The indices of duration in the delta, theta and alpha ranges of the EEG of MR subjects were increased, and the indices of the duration of beta rhythms – decreased. 3. When analyzing FMPA in MR persons, it turned out that in right-handers the negativeness of FMPA indices increased, and in left-handers there was an increase in the positivity of FMPA indices.

The incidence and pathophysiology of neurological symptoms in COVID-19

Russian Military Medical Academy Reports ◽

10.17816/rmmar83617 ◽

2021 ◽

Vol 40 (4) ◽

pp. 33-42

Author(s):

Igor V. Litvinenko ◽

Miroslav M. Odinak ◽

Nikolay V. Tsygan ◽

Aleksander V. Ryabtsev

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Rare Complication ◽

Cranial Nerves ◽

Neurological Symptoms ◽

Immune Mediated ◽

High Incidence ◽

Coronavirus Infection

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)

Progress in Research on SARS-CoV-2 Infection Causing Neurological Diseases and Its Infection Mechanism

Frontiers in Neurology ◽

10.3389/fneur.2020.592888 ◽

2021 ◽

Vol 11 ◽

Author(s):

Lintao Wang ◽

Zhiguang Ren ◽

Li Ma ◽

Yanjie Han ◽

Wenqiang Wei ◽

...

Keyword(s):

Public Health ◽

Central Nervous System ◽

Nervous System ◽

Neurological Diseases ◽

Public Health Problem ◽

Major Public Health Problem ◽

The Impact ◽

Great Harm

COVID-19 has spread rapidly worldwide since its outbreak and has now become a major public health problem. More and more evidence indicates that SARS-CoV-2 may not only affect the respiratory system but also cause great harm to the central nervous system. Therefore, it is extremely important to explore in-depth the impact of SARS-CoV-2 infection on the nervous system. In this paper, the possible mechanisms of SARS-CoV-2 invading the central nervous system during COVID-19, and the neurological complications caused by SARS-CoV-2 infection were reviewed.

Bing-Neel Syndrome Case Report: A Previously Undocumented IgG Variant with MRI, PET/CT, and PET/MRI Imaging

Case Reports in Hematology ◽

10.1155/2016/3931709 ◽

2016 ◽

Vol 2016 ◽

pp. 1-4 ◽

Cited By ~ 2

Author(s):

Daniel Halperin ◽

Simon Hallam ◽

Athar Haroon ◽

Tom Butler ◽

Samir Agrawal

Keyword(s):

Central Nervous System ◽

Cerebrospinal Fluid ◽

Nervous System ◽

Case Report ◽

Lymphoplasmacytic Lymphoma ◽

Mri Imaging ◽

Pet Ct ◽

Waldenstrom’S Macroglobulinaemia

Waldenstrom’s macroglobulinaemia is the most commonly reported subtype of lymphoplasmacytic lymphoma (LPL); it is characterised by IgM secretion. Neurological complications are common usually as a result of hyperviscosity. In rare cases, cells can infiltrate the central nervous system; this is known as Bing-Neel syndrome. We report the case of a 57-year-old male with lymphoplasmacytic lymphoma of the IgG-subtype with neurological symptoms and the consequent finding of lymphoplasmacytoid cells in his cerebrospinal fluid as well as deposits on MRI and PET-CT imaging. This is the first report of Bing-Neel syndrome in IgG-subtype LPL. We discuss the biological and radiological markers of his disease, including PET imaging, which has been minimal in this area to date.

Tembusu Virus entering the central nervous system caused nonsuppurative encephalitis without disrupting the blood-brain barrier

Journal of Virology ◽

10.1128/jvi.02191-20 ◽

2021 ◽

Author(s):

Sheng Yang ◽

Yufei Huang ◽

Yonghong Shi ◽

Xuebing Bai ◽

Ping Yang ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Blood Brain Barrier ◽

Neurological Symptoms ◽

Brain Barrier ◽

Poultry Industry ◽

Blood Brain ◽

Tembusu Virus ◽

The Brain

Tembusu Virus (TMUV) is an emerging and re-emerging zoonotic pathogen that adversely affects poultry industry in recent years. TMUV disease is characterized by nonsuppurative encephalitis in ducklings. The duckling infection model was established to study the mechanism of TMUV crossing the blood-brain barrier (BBB) into the central nervous system (CNS). Here, we showed that no obvious clinical symptoms and enhancement of BBB permeability occurred at the early stage of infection (3∼5 dpi). While simultaneously virus particles were observed by transmission electron microscopy in the brain, inducing the accumulation of inflammatory cytokines. Neurological symptoms and disruption of BBB appeared at the intermediate stage of infection (7∼9 dpi). It was confirmed that TMUV could survive and propagate in brain microvascular endothelial cells (BMECs), but did not affect the permeability of BBB in vivo and in vitro at an early date. In conclusion, TMUV enters the CNS then causes encephalitis, and finally destruct the BBB, which may be due to the direct effect of TMUV on BMECs and the subsequent response of “inflammatory storm”. IMPORTANCE The TMUV disease has caused huge losses to the poultry industry in Asia, which is potentially harmful to public health. Neurological symptoms and their sequelae are the main characters of this disease. However, the mechanism of how this virus enters the brain and causes encephalitis is unclear. In this study, we confirmed that the virus entered the CNS and then massively destroyed BBB and the BBB damage was closely associated with the subsequent outbreak of inflammation. TMUV may enter the CNS through the transcellular and “Trojan horse” pathways. These findings can fill the knowledge gap in the pathogenesis of TMUV-infected poultry and be benefit for the treatment of TMUV disease. What’s more, TMUV is a representative to study the infection of avian flavivirus. Therefore, our studies have significances both for understanding of the full scope of mechanisms of TMUV and other flavivirus infection, and conceivably, for therapeutics.