British Neuropsychiatry Annual Meeting 2021

The proceedings contain 40 papers. The topics discussed include: sex, bugs microwave attacks: how bad science, mating insects psychogenic illness created an international incident with Cuba;Covid-19 and neuropsychiatry;clinical update on delirium;fibromyalgia and myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS): an interoceptive predictive coding model of pain and fatigue expression;when the spark goes out: the neurology of apathy and motivation;is subjective cognitive decline (SCD) a better marker of susceptibility to functional cognitive disorder (FCD) than to neurodegeneration?: the caerphilly prospective study;temporal and spectral dynamics of reward and risk processing in the amygdala revealed with stereo-EEG recordings in epilepsy;a systematic review of extra-motor symptom evaluation in clinical trials for amyotrophic lateral sclerosis;and stimulation of the ventrolateral prefrontal cortex speeds up evidence accumulation in conflictual-uncertain environments.

Novel Framework for Neurocognitive Covid-19 Assessment

Background The neurotrophic effects of Covid-19 are becoming increasingly recognized, with altered mental state now being the second most common presenting complaint insert numbers. A key question is whether this has long term consequences. Cognitive problems are commonly reported in patients 3 months after acute infection as part of the so called Long-Covid syndrome. However, the underlying cause is not well understood. Candidate explanations include legacy from encephalitis and stroke;however, other complications such as the sequelae, delirium, remain underexplored. Furthermore, little consideration has been given to functional cognitive disorders and the cognitive consequences of depression, anxiety and fatigue. Aims We propose a structured approach to clinical assessment for clinicians reviewing late cognitive complaints after COVID 19. Methods We created our own unique framework for neurocognitive Covid assessment based upon a review of the literature. Results Covid status- Any positive test. If not review of core symptoms such as breathlessness, headache, anosmia, nasal obstruction, cough, myalgia, or gustatory dysfunction;duration, extent of exposure to Covid confirmed cases. Consider rapid antibody testing. Neuropsychiatric history- Part 1 symptoms at onset- in particular disruptions of consciousness and altered mental state. Acute memory impairment, anterograde/retrograde and with/ without a temporal gradient. neurocognitive function. ITU admission and oxygen requirements. Part 2 Current cognitive and mental state- in addition to standard history seek evidence of internal inconsistency of memory symptoms and attentional dysregulation. Has social cognition and meta-cognition been affected. Note attribution bias i.e. no Im not depressed, I cant enjoy anything because of my symptoms Background history- subtle suggestion of neurodegeneration and depression, anxiety and functional symptoms should be explored. MRI findings- signal changes in the medial temporal lobe, nonconfluent multifocal white matter hyperintense lesions, and isolated white matter microhemorrhages. Novel biomarkers IL-6, MCP-1, and IP-10. Conclusion Cognitive symptoms are common after confirmed and assumed COVID exposure. We propose a framework for neuropsychiatric assessment and the use of adjuvant imaging and potential biomarkers.

The possibilities of using the effects of ozone therapy in neurology

OBJECTIVES: The beneficial effects of ozone therapy consist mainly of the promotion of blood circulation: peripheral and central ischemia, immunomodulatory effect, energy boost, regenerative and reparative properties, and correction of chronic oxidative stress. Ozone therapy increases interest in new neuroprotective strategies that may represent therapeutic targets for minimizing the effects of oxidative stress. METHOD(S): The overview examines the latest literature in neurological pathologies treated with ozone therapy as well as our own experience with ozone therapy. The effectiveness of treatments is connected to the ability of ozone therapy to reactivate the antioxidant system to address oxidative stress for chronic neurodegenerative diseases, strokes, and other pathologies. Application options include large and small autohemotherapy, intramuscular application, intra-articular, intradiscal, paravertebral and epidural, non-invasive rectal, transdermal, mucosal, or ozonated oils and ointments. The combination of different types of ozone therapy stimulates the benefits of the effects of ozone. RESULT(S): Clinical studies on O2-O3 therapy have been shown to be efficient in the treatment of neurological degenerative disorders, multiple sclerosis, cardiovascular, peripheral vascular, orthopedic, gastrointestinal and genitourinary pathologies, fibromyalgia, skin diseases/wound healing, diabetes/ulcers, infectious diseases, and lung diseases, including the pandemic disease caused by the COVID-19 coronavirus. CONCLUSION(S): Ozone therapy is a relatively fast administration of ozone gas. When the correct dose is administered, no side effects occur. Further clinical and experimental studies will be needed to determine the optimal administration schedule and to evaluate the combination of ozone therapy with other therapies to increase the effectiveness of treatment.Copyright © 2021 Neuroendocrinology Letters.

COVID-19 and neurodegenerative diseases: reciprocal impacts, medical care strategies and underlying mechanisms

Objective: To elucidate the relationship between COVID-19 and neurodegenerative diseases. Background(s): Recently, the impact of the COVID-19 pandemic on patients with neurodegenerative disease, as well as the specific neurological manifestations of COVID-19 have aroused great interests. However, there are still many issues of concern to us that need to be clarified. Method(s): We reviewed the current literature on the complex relationship between neurodegenerative diseases [including Parkinson's disease (PD) and Alzheimer's disease (AD)] and COVID-19. We summarized the impact of COVID-19 infection on symptom severity, disease progression and mortality of neurodegenerative disease, and discussed whether COVID-19 infection could trigger neurodegenerative disease. The vulnerability to COVID-19 infection and prognosis of COVID-19 positive individuals in patients with neurodegenerative disease were also included. Modification of care strategy, specific drug therapies and vaccines during the pandemic were also listed. At last, mechanisms underlying the link between COVID-19 and neurodegenerative disease were reviewed. Result(s): There is an interaction between COVID-19 infection and neurodegenerative diseases, including worsening symptomatic severity and accelerating neurodegeneration by COVID-19 infection in PD and AD patients, and vice versa, neurodegenerative diseases increasing the vulnerability to COVID-19 infection and enhancing the risks of hospitalization and death after virus infection. Many potential molecular and cellular pathways were hypothesized to be the link between COVID-19 infection and neurodegenerative diseases, but further studies are still needed to verify the mechanisms. COVID-19 pandemic has profoundly changed the way of medical care, telemedicine, vaccines and specific drug therapies are promising for the better management of PD and AD patients [Table 1] [Table2]. Conclusion(s): COVID-19 and neurodegenerative diseases have reciprocal impact on each other.

The relationship between Parkinson's disease and Coronavirus 2019 (COVID-19)

Background: The main trigger for Parkinson's disease is a mutated version of a protein called alpha-synuclein.This protein accumulates in dopamine-producing neurons. COVID-19 can increase the risk of Parkinson's and other neurological diseases. Methods:This review study was conducted by the library method. Results: The results showed that the virus can cause neuroinflammation, which, as a predisposing event, predisposes the brain to overreaction to subsequent neurological events. This secondary neurological event can be anything from another viral infection to poisoning and even aging. A secondary neurological event triggers an abnormal brain response that leads to nerve degeneration and eventually Parkinson's disease. The results show that the SARS-CoV-2 virus as a neurotropic virus can enter brain tissue. Conclusion: Therefore, the virus certainly has the potential to act as a predisposing event in increasing the risk of Parkinson's disease.

Pathomorphological changes in some organs and tissues of COVID-19 convalescent patients

New coronavirus infection (COVID-19) is highly contagious viral disease caused by SARS-CoV-2 leading to the pandemic. The autopsy of COVID-19 patients often showed features of previous brain diseases including neurodegeneration, previous strokes, demyelinating diseases and atherosclerosis. Patients with acute cerebrovascular accidents and severe COVID-19 had higher numbers of lethality in comparison to non-severe course of infection without cerebrovascular accidents. A comparative analysis of morphological changes in lungs of deceased patients who died in different periods of first clinical symptoms is to be conducted. Objective. Description of pathomorphological changes in deceased patients during the period of reconvalescence. Patients and methods. The analysis of 15 fatal cases which took place in Botkin Hospital with the diagnosis of ischemic stroke and new coronavirus infection in the previous 2-4 months has been held. Macro and microscope examination of brain, lungs, brachiocephalic arteries, kidneys and liver has been carried out. Results. All patients had morphological features of ischemic damage of grey matter in the brain. Beside necrosis of neurocytes with diffuse infiltration in the grey matter, hematoxylin cycles were found, in some cases they were placed in a perivascular way in choroid plexus. Also 5 patients suffered a myocardial infarction up to 3 days. 10 patients had structures disorganisation in areas of lung parenchyma with hystoacrchitectonic changes because of the fibrosis. Alveoli in some places collaborated mostly with single airway clearance. The fact that most patients had lung hemosiderosis can prove coronavirus infection suffered earlier with microcirculatory bed damage. Conclusion. Thus, morphological changes seen in the period of reconvalescence of COVID-19 is a result of pathomorphosis of changes described earlier for acute period of coronavirus infection and affect not only lungs, but also other organs and tissues. This proves systematic characteristic of the infection.

Donepezil Beyond Alzheimer’s Disease? A Narrative Review of Therapeutic Potentials of Donepezil in Different Diseases

Donepezil hydrochloride is an acetylcholine esterase inhibitor studied and approved to treat Alzheimer’s disease (AD). However, this drug can have positive therapeutic potential in treating different conditions, including various neurodegenerative disorders such as other types of dementia, multiple sclerosis, Parkinson’s disease, psychiatric and mood disorders, and even infectious diseases. Hence, this study reviewed the therapeutic potential of this drug in treating Alzheimer’s and other diseases by reviewing the articles from databases including Web of Science, Scopus, PubMed, Cochrane, and Science Direct. It was shown that donepezil could affect the pathophysiology of these diseases via mechanisms such as increasing the concentration of acetylcholine, modulating local and systemic inflammatory processes, affecting acetylcholine receptors like nicotinic and muscarinic receptors, and activating various cellular signaling via receptors like sigma-1 receptors. Despite many therapeutic potentials, this drug has not yet been approved for treating non-Alzheimer’s diseases, and more comprehensive studies are needed.

45th Annual Meeting of the American Society of Neuroimaging

The proceedings contain 31 papers. The topics discussed include: brain abscess appearing 20 years post craniotomy;postoperative diffusion restriction in the proximal optic nerve: optic neuropathy or central retinal artery occlusion?;magnetic resonance imaging as a prognostic disability marker in clinically isolated syndrome: a systematic review;bilateral internuclear ophthalmoplegia caused by unilateral infarction;neuroaspergillosis in a patient with chronic lymphocytic leukemia as progressively worsening ischemic infarct;neuroimaging in mitochondrial short-chain enoyl-coa hydratase 1 deficiency: a progressive encephalomyelopathy starting in utero;childhood-onset neurodegeneration with brain atrophy: imaging findings of a rare diagnosis;multiple sclerosis associated with Balo-like lesions post-coronavirus disease 2019;and within-subject reproducibility of quantitative proton density mapping.

INFECTIOUS HYPOTHESIS OF NEURODEGENERATIVE DISEASES. WHAT WAITS US AFTER THE COVID-19 PANDEMIC?

Since the description of the first clinical cases of the most common neurodegenerative diseases, numerous hypotheses have been proposed for their development. At the same time, the failure of therapeutic strategies in various directions of clinical research indicates the fallacy of most theories. In this regard, in recent years, various infectious agents are increasingly considered as a trigger of neuronal inflammation and a factor inducing the onset of the neurodegenerative process. Infectious agents differ in their mechanisms of invasion into the central nervous system and can even enter the brain perineurally. Reactivation of latent viral infection induces the production of viral proteins and the accumulation of abnormal proteins that are markers of Alzheimer's disease and Parkinson's disease. Both bacterial (chlamydia, causative agents of chronic periodontitis, E. coli) and viral (herpes viruses, noroviruses) infectious agents are considered. However, for the development of neurodegeneration, it is not enough just a simple invasion and reactivation of the infectious process: the genetic characteristics of the main histocompatibility complex also play a huge role. Currently, several studies have been initiated on the possible efficacy of antibacterial and antiviral drugs in Alzheimer's disease. Data obtained over the past year suggests that the brain may act as a target for SARS-CoV-2. Neurological manifestations of COVID-19 can occur as a result of both the direct cytopathic action of the pathogen and the activation of neuroinflammation, accompanied by a violation of the integrity of the blood-brain barrier. Further study of the molecular and cellular mechanisms of neuroinflammation and neurodegeneration in COVID-19 will form the basis for the development of treatments for neurological complications.

Blood-Based Biomarkers for COVID-19-Associated Neurological Outcomes

Background: There are no blood screening tests to assess brain molecular alterations linked to neurological alterations in human coronavirus disease 2019 (COVID-19). Evidence indicates long-term brain abnormalities associated with SARS-CoV-2 infection, including cognitive impairment, which may develop into an emerging health problem as many patients are emerging with cognitive abnormalities that may be associated to an increased risk of AD. Promising results from the field of blood-based biomarkers are emerging with the use of extracellular vesicles (EVs). Neuronal-derived EVs (NDEVs) can be isolated from the total pool of EVs in the blood to investigate biomarkers of brain diseases. Methods: Isolation of NDEVs was performed using the ExoQuick ULTRA EV Isolation System, followed by immunoprecipitation with L1CAM antibody. EVs were characterized by nanoparticle tracking analysis, electron microscopy, Exo-Check Array, and ELISA/immunoblotting to detect exosome proteins. Biomarker measurements in the plasma, CSF and EVs from plasma was done by ELISA. A broader analysis of isolated EVs was done by Mass spectrometry. Results: Levels of cytokines were increased in the blood samples from a cohort of 100 COVID-19 patients compared to controls. We had the opportunity to investigate biomarkers in the CSF of 38 patients and observed that the levels of cytokines and biomarkers of neurodegeneration in CSF samples were increased. Conclusions: COVID-19 was associated with increases in CSF and blood cytokines and markers of neurodegeneration. A close follow up in patients that developed COVID-19 symptoms is important to determine the long-term consequences of infection Funding Source: CNPq, FAPERJ, CIHR Keywords: Extracellular Vesicles, Biomarkers, COVID-19

Longitudinal changes of neurospecific serum proteins in COVID-19 patients

INTRODUCTION/HYPOTHESIS: COVID-19 has been associated with distinct types of neuronal damage. We hypothesize that the progression of neurological damage will be related to an imbalance between neurodegeneration, neuroinflammatory, and neuroprotective markers, therefore suggesting a potential mechanism for the emergence of adverse, chronic outcomes. METHODS: 105 patients admitted to an urban, academic hospital with a diagnosis of COVID-19 were enrolled. Serum neuroprotective (clusterin, fetuin), neurodegenerative (τ, phosphorylated τ, amyloids, TDP43, NRGN, NCAM-1, and KLK6), and neuroinflammatory (CCL23, YKL40, MIF) markers were collected. These were analyzed longitudinally in conjunction with immune system activators (RAGE, IL-34) using the multiplex platform. Electronic medical records were used to collect demographic and clinical data. RESULTS: Of the 105 patients, 5 were diagnosed with stroke within 28 days of admission, followed by an additional 6 strokes occurring by 6 months, or a 9.5% occurrence of stroke overall. Serum levels of Amyloid β42 declined significantly for the general population 7 days after admission when compared to initial collections (p< 0.001), while Amyloid β40, KLK6, and MIF declined and recovered within the same 7 days (p< 0.001, p< 0.001, p=0.003). The neuroprotective markers fetuin and clusterin were particularly dynamic with fetuin decreasing and restoring in less than 7 days (p=0.02) and clusterin remaining low after admission (p< 0.001). Most patients had persistently elevated CCL23 levels, with the stroke patient cohort having the highest values (p=0.018). The IL-6 levels of stroke patients were significantly higher compared to their non-stroke counterparts one week after admission (p=0.001), while IL-8 levels fluctuated before declining (p< 0.001). CONCLUSIONS: Our data reveals elevations in neuronal damage in the 7 days following hospital admission for COVID-19 patients. The down-regulation of fetuin and clusterin is particularly compelling as their declines may be linked to the elevated neuronal injury seen with increased neuroinflammatory markers, specifically CCL23 and IL-6. Serum levels of neurodegeneration markers proved complex, therefore possibly suggesting a more dynamic relationship to the neural abnormalities seen in COVID-19 patients.