Neurological complications of COVID-19.

Corona Virus Disease 2019 (COVID-19) has caused several pandemic peaks worldwide due to its high variability and infectiousness, and COVID-19 has become a long-standing global public health problem. There is growing evidence that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) frequently causes multi-organ injuries and more severe neurological manifestations. Therefore, increased awareness of possible neurological complications is beneficial in preventing and mitigating the impact of long-term sequelae and improving the prognostic outcome of critically ill patients with COVID-19. Here, we review the main pathways of SARS-CoV-2 neuroinvasion and the potential mechanisms causing neurological damage. We also discuss in detail neurological complications, aiming to provide cutting-edge basis for subsequent related basic research and clinical studies of diagnosis and treatment.

Neurological Dysfunction in Long COVID Should Not Be Labelled as Functional Neurological Disorder.

There have been suggestions that Long COVID might be purely functional (meaning psychological) in origin. Labelling patients with neurological dysfunction in Long COVID as having functional neurological disorder (FND) in the absence of proper testing may be symptomatic of that line of thought. This practice is problematic for Long COVID patients, as motor and balance symptoms have been reported to occur in Long COVID frequently. FND is characterized by the presentation of symptoms that seem neurological but lack compatibility of the symptom with a neurological substrate. Although diagnostic classification according to the ICD-11 and DSM-5-TR is dependent predominantly on the exclusion of any other medical condition that could account for the symptoms, current neurological practice of FND classification allows for such comorbidity. As a consequence, Long COVID patients with motor and balance symptoms mislabeled as FND have no longer access to Long COVID care, whereas treatment for FND is seldom provided and is ineffective. Research into underlying mechanisms and diagnostic methods should explore how to determine whether motor and balance symptoms currently diagnosed as FND should be considered one part of Long COVID symptoms, in other words, one component of symptomatology, and in which cases they correctly represent FND. Research into rehabilitation models, treatment and integrated care are needed, which should take into account biological underpinnings as well as possible psychological mechanisms and the patient perspective.

[Neurointensive care medicine and COVID-19]. / Neurointensivmedizin und COVID-19.

This review article summarizes important findings on the interfaces between the coronavirus disease 2019 (COVID-19) pandemic and neurology with an emphasis of the implications for neurointensive care medicine. More specifically, the prevalence, pathomechanisms and impact of neurological manifestations are reported. The most common neurological manifestations of critically ill COVID-19 patients are cerebrovascular complications, encephalopathies and intensive care unit-acquired weakness (ICUAW). A relevant direct pathophysiological effect by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) itself has not yet been established with certainty. In fact, indirect systemic inflammatory processes triggered by the viral infection and side effects of intensive care treatment are much more likely to cause the reported sequelae. The impact of the pandemic on patients with neurological disorders and neurointensive care medicine is far-reaching but not yet sufficiently studied.

Exploring the management approaches of cytokines including viral infection and neuroinflammation for neurological disorders.

Considerable evidence supports that cytokines are important mediators of pathophysiologic processes within the central nervous system (CNS). Numerous studies have documented the increased production of various cytokines in the human CNS in various neurological and neuropsychiatric disorders. Deciphering cytokine actions in the intact CNS has important implications for our understanding of the pathogenesis and treatment of these disorders. The purpose of this study is to discuss the recent research on treating cytokine storm and amyloids, including stroke, Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's condition, Multi-sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS). Neuroinflammation observed in neurological disorders has a pivotal role in exacerbating Aß burden and tau hyperphosphorylation, suggesting that stimulating cytokines in response to an undesirable external response could be a checkpoint for treating neurological disorders. Furthermore, the pro-inflammatory cytokines help our immune system through a neuroprotective mechanism in clearing viral infection by recruiting mononuclear cells. This study reveals that cytokine applications may play a vital role in providing novel regulation and methods for the therapeutic approach to neurological disorders and the causes of the deregulation, which is responsible for neuroinflammation and viral infection. However, it needs to be further investigated to clarify better the mechanisms of cytokine release in response to various stimuli, which could be the central point for treating neurological disorders.

Training of neurologists for the 21st century: cultural and professional skills.

Training of neurologists for the near future is a challenge due to the likely advances in neuroscientific methods, which will change much of our knowledge on diagnosis and treatment of neurological diseases. OBJECTIVE: to comment on what may be more likely to be a constant in the very near future and to recommend how to prepare the neurologist for the 21st century. METHODS: through a critical review of recent articles on the teaching of Neurology, to present a personal view on the subject. RESULTS: Diagnostic methods and therapeutic resources in Neurology will be greatly improved, but the central core of teaching young neurologists will continue to be the clinical/anatomical correlation. The neurologist must be prepared to be the primary physician in the care of patients with neurological disorders, although the roles of consultant and clinical neuroscientist must also be considered. In addition to technical knowledge, the neurologist must be prepared to discuss not only distressing issues related to the specialty, such as the risks of genetic diseases for family members of their patients, the inexorable progression of some diseases and the need for palliative care, but also problems not directly related to Neurology that cause anxiety and depression in the patient or that are the main reason for the initial consultation. CONCLUSION: neurology will be an even more important area of medicine and the neurologist must be well prepared to be the primary doctor to diagnose, treat and follow the patient with neurological disorders. In addition to technical knowledge, training in doctor-patient relations should be highlighted.

The impact of COVID-19 on patients with neurological disorders and their access to healthcare in Africa: A review of the literature.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has hampered the progress of neurological healthcare services for patients across Africa. Before the pandemic, access to these services was already limited due to elevated treatment costs among uninsured individuals, shortage of medicines, equipment, and qualified personnel, immense distance between residing areas and neurological facilities, and a limited understanding of neurological diseases and their presentation by both the health workers and the African population. METHODOLOGY: The databases PubMed, Google Scholar, Science Direct, and the National Library of Medicine were searched for literature. All articles on neurological disorders in Africa were considered. AIM: This review article explores the challenges of providing the best services for patients suffering from neurological disorders in Africa amid the COVID-19 pandemic and provides evidence-based recommendations. RESULTS: As Africa's governments made more resources available to support patients affected by COVID-19, neurological care received less priority and the capacity and competency to treat patients with neurological disorders thus suffered substantially. Both short-term and long-term strategies are needed to improve the quality of neurological services after the pandemic in the region. CONCLUSION: To strengthen Africa's neurological services capability during and after the COVID-19 pandemic, African governments must ensure appropriate healthcare resource allocation, perform neurology management training, and increase health security measures in medication supply. Long-term strategies include incorporating responsible finance and resource procurement and advancement of tele-neurology. International collaboration is essential to promote the sustainable improvement of neurological services in Africa.

A questionnaire-based survey of acceptability and satisfaction of virtual neurology clinic during COVID-19 lockdown: a preliminary study.

INTRODUCTION: Telemedicine during this pandemic acts as a lifeline for many non-COVID patients especially with chronic neurological diseases. The aim of present study was to evaluate cost effectiveness and level of satisfaction amongst patients from teleneurology outpatient department (OPD). METHODS: An online cross-sectional survey, having questions both in Hindi and English was conducted via telemedicine facility at Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. Demographic variables, illness details, travel distance and time taken, travel expenditure, level of satisfaction and preferred choice among tele OPD versus in-person OPD once pandemic ends were recorded. RESULTS: Total 1388 patients filled the online COVID-19 teleneurology survey google form. Mean age was 39.21 ± 16.72 years. Majority (N = 824, 59%) were males. Six hundred (43%) patients' educational qualification were ≤ 10th standard. Majority of patients (N = 840, 60.5%) belonged to the rural background. Headache (N = 424, 30.5%) followed by backache (N = 220, 16%), stroke (N = 176, 13%) and seizure (N = 148, 11%) were the common illnesses. Travel time of > 5 hours was saved in 496 (36%) patients and travel expenditure of > Rs100 in 796 (57%) patients. About 96% (N = 1332) felt satisfied with the treatment advice via teleconsultation. DISCUSSION: Teleneurology facility is not only feasible but also affordable and acceptable in various neurological conditions. The chief reasons being no waiting time, saving of travelling time and travel expenditure with good satisfaction.

European Academy of Neurology 2019 - 2022.

BACKGROUND: The EAN was founded in 2014 with the mission of reducing the burden of neurological disorders. METHODS: In 2019 the society defined four strategic priorities: education, science, membership, and advocacy. This paper reviews the EAN development in the last 3 years. RESULTS: The outbreak of COVID-19 pandemic in 2020 had a profound impact on the entire world and triggered profound changes in the EAN including the implementation of new digital technologies. Education The virtual congress in 2020 was the best attended in history (43,844 registrations). The European Training Requirements for Neurology was revised. A mentorship program and a student section were created. A state-of-the-art eLearning platform will be launched in 2022. Research To assess neurological manifestations of COVID-19 an international registry (ENERGY) was created. Studies on the burden of neurological disorders and sleep disorders, respectively, were started. The first EAN science school took place in 2022. Membership The EAN includes 45,000 members and 47 national societies. New task forces were created on gender and diversity, tele- and general neurology. Advocacy In 2022 the EAN supported the adoption of the Global Action Plan on epilepsy and other neurological disorders by the WHO and the neurological community in the Ukraine. The same year the EAN launched a Brain Health Strategy promoting a non-disease and -age centred, lifelong holistic approach ('one brain, one life, one approach'). CONCLUSION: The ongoing pandemic and wars demonstrate the fragility of our political and health systems and the need for people centeredness, international collaborations, solidarity, and digitalization. The EAN will continue promoting excellence in neurological care, science and education as well as brain health for all.

Acute Neurologic Complications of COVID-19 and Postacute Sequelae of COVID-19.

Neurologic complications can be seen in mild to severe COVID-19 with a higher risk in patients with severe COVID-19. These can occur as a direct consequence of viral infection or consequences of treatments. The spectrum ranges from non-life-threatening, like headache, fatigue, malaise, anosmia, dysgeusia, to life-threatening complications, like stroke, encephalitis, coma, Guillain-Barre syndrome. A high index of suspicion can aid in early recognition and treatment. Outcomes depend on severity of underlying COVID-19, patient age, comorbidities, and severity of the complication. Postacute sequelae of COVID-19 range from fatigue, headache, dysosmia, brain fog, anxiety, depression to an overlap with postintensive care syndrome.

Neuroimmune disorders in COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the aetiologic agent of the coronavirus disease 2019 (COVID-19), is now rapidly disseminating throughout the world with 147,443,848 cases reported so far. Around 30-80% of cases (depending on COVID-19 severity) are reported to have neurological manifestations including anosmia, stroke, and encephalopathy. In addition, some patients have recognised autoimmune neurological disorders, including both central (limbic and brainstem encephalitis, acute disseminated encephalomyelitis [ADEM], and myelitis) and peripheral diseases (Guillain-Barré and Miller Fisher syndrome). We systematically describe data from 133 reported series on the Neurology and Neuropsychiatry of COVID-19 blog ( https://blogs.bmj.com/jnnp/2020/05/01/the-neurology-and-neuropsychiatry-of-covid-19/ ) providing a comprehensive overview concerning the diagnosis, and treatment of patients with neurological immune-mediated complications of SARS-CoV-2. In most cases the latency to neurological disorder was highly variable and the immunological or other mechanisms involved were unclear. Despite specific neuronal or ganglioside antibodies only being identified in 10, many had apparent responses to immunotherapies. Although the proportion of patients experiencing immune-mediated neurological disorders is small, the total number is likely to be underestimated. The early recognition and improvement seen with use of immunomodulatory treatment, even in those without identified autoantibodies, makes delayed or missed diagnoses risk the potential for long-term disability, including the emerging challenge of post-acute COVID-19 sequelae (PACS). Finally, potential issues regarding the use of immunotherapies in patients with pre-existent neuro-immunological disorders are also discussed.

Extending human healthspan and longevity: a symposium report.

For many years, it was believed that the aging process was inevitable and that age-related diseases could not be prevented or reversed. The geroscience hypothesis, however, posits that aging is, in fact, malleable and, by targeting the hallmarks of biological aging, it is indeed possible to alleviate age-related diseases and dysfunction and extend longevity. This field of geroscience thus aims to prevent the development of multiple disorders with age, thereby extending healthspan, with the reduction of morbidity toward the end of life. Experts in the field have made remarkable advancements in understanding the mechanisms underlying biological aging and identified ways to target aging pathways using both novel agents and repurposed therapies. While geroscience researchers currently face significant barriers in bringing therapies through clinical development, proof-of-concept studies, as well as early-stage clinical trials, are underway to assess the feasibility of drug evaluation and lay a regulatory foundation for future FDA approvals in the future.

[NEUROLOGICAL COMPLICATIONS OF COVID-19: REVIEW OF LITERATURE AND OWN EXPERIENCE].

According to the literature, the main neurological complications of COVID-19 are hyposmia, hypogeia, headache, dizziness, myalgia, and severe neurological syndromes like encephalopathy, stroke, and coma. The mechanisms of neurological complications of the acute period are direct viral damage, hypoxic damage, and immune damage due to the activation of inflammation, including autoantibodies. After the end of the acute phase of the disease, neurological complications in the form of asthenic syndrome, vascular syndrome, exacerbation of chronic diseases (deterioration of cognitive and communication functions in patients with autism, schizophrenia, exacerbation of autoimmune neurological diseases, aggravation of the condition of patients with tics, increased frequency of epileptic seizures in adults and children, resumption of epileptic seizures in patients who were previously in stable remission, the debut of epileptic seizures). These disorders are based on the following mechanisms: neuroinflammation, activation of pro-inflammatory cytokines (IL-1, -2, -6, -8, -10, -17, -18, CXCL10, CCL2), formation of autoantibodies, increased permeability of the blood-brain barrier, mitochondrial dysfunction, adrenal and thyroid dysfunction, venous dyscirculation. In the treatment of neurological complications after a COVID-19 infection, it is advisable to use anti-inflammatory therapy, mitochondrial therapy (including the technique of intermittent hypoxic-hyperoxic therapy), detoxication, correction of hormonal status (primarily the state of the adrenal glands and thyroid gland), vasoactive therapy, and symptomatic therapy.

Impact of Covid-19 on the therapeutic plasma exchange service within the South East Asian region: Consensus recommendations and global perspectives.

INTRODUCTION: Therapeutic plasma exchange (TPE) for neuroimmunological disorders has played an increasingly important role within the Southeast Asian (SEA) region. The South East Asian Therapeutic Plasma exchange Consortium (SEATPEC) was formed in 2018 to promote education and research on TPE within the region. The advent of the Covid-19 pandemic has produced challenges for the development and expansion of this service. METHODOLOGY: A qualitative and semi-quantitative questionnaire-based survey was conducted by SEATPEC member countries from January to June 2020 (Phase 1) and then from July 2020 to January 2021 in (Phase 2) to assess the impact of Covid-19 on regional TPE. OBJECTIVES: The study's main objectives were to explore the challenges experienced and adaptations/adjustments taken by SEATPEC countries in order to continue safe and efficient TPE during the Covid-19 pandemic. RESULTS: The pandemic was found to disrupt the delivery of TPE services in all SEATPEC countries. Contributing factors were multifactorial due to overstretched medical services, staff shortages, quarantines and redeployments, fear of acquiring Covid-19, movement restriction orders, and patient's psychological fear of attending hospitals/testing for Covid-19. All SEATPEC countries practiced careful stratification of cases for TPE (electives vs emergencies, Covid-19 vs non-Covid-19 cases). SEATPEC countries had to modify TPE treatment protocols to include careful preprocedure screening of patient's for Covid-19, use of personal protective equipment (PPE) and post-TPE sanitization of machines and TPE suites. CONCLUSION: Based on the responses of the survey, SEATPEC countries produced a consensus statement with five recommendations for safe and effective TPE within the region.

Neuroscience20 (BRAIN20, SPINE20, and MENTAL20) Health Initiative: A Global Consortium Addressing the Human and Economic Burden of Brain, Spine, and Mental Disorders Through Neurotech Innovations and Policies.

Neurological disorders significantly impact the world's economy due to their often chronic and life-threatening nature afflicting individuals which, in turn, creates a global disease burden. The Group of Twenty (G20) member nations, which represent the largest economies globally, should come together to formulate a plan on how to overcome this burden. The Neuroscience-20 (N20) initiative of the Society for Brain Mapping and Therapeutics (SBMT) is at the vanguard of this global collaboration to comprehensively raise awareness about brain, spine, and mental disorders worldwide. This paper aims to provide a comprehensive review of the various brain initiatives worldwide and highlight the need for cooperation and recommend ways to bring down costs associated with the discovery and treatment of neurological disorders. Our systematic search revealed that the cost of neurological and psychiatric disorders to the world economy by 2030 is roughly $16T. The cost to the economy of the United States is $1.5T annually and growing given the impact of COVID-19. We also discovered there is a shortfall of effective collaboration between nations and a lack of resources in developing countries. Current statistical analyses on the cost of neurological disorders to the world economy strongly suggest that there is a great need for investment in neurotechnology and innovation or fast-tracking therapeutics and diagnostics to curb these costs. During the current COVID-19 pandemic, SBMT, through this paper, intends to showcase the importance of worldwide collaborations to reduce the population's economic and health burden, specifically regarding neurological/brain, spine, and mental disorders.

Neurological symptoms of COVID-19 infection; a cross-sectional study on hospitalized COVID-19 patients in Iran.

BACKGROUND: Coronavirus disease 2019 (COVID-19), a global issue now, can have a variety of clinical manifestations. Hundreds of articles have discussed different aspects of this infectious disease, such as physiopathology, epidemiology, clinical manifestations and treatment protocols. Recently, neurological manifestations of the disease have been found to be pretty common among COVID-19 patients. Here, neurological symptoms of COVID-19 infection with a focus on non-cerebrovascular complications are discussed in a large study population. METHODS: Neurological symptoms of 891hospitalized COVID-19 patients from March to June 2020 in a major Hospital, Tehran, Iran, were reviewed. Demographic characteristics and neurological manifestations were analyzed. RESULTS: Among 891 hospitalized COVID-19 patients, the following symptoms were observed: headache (63.9%), sleeping problems (51.3%), hyposmia/anosmia (46%), dizziness (45.4%), hypogeusia (42.1%), memory issues (31.5%), auditory disturbances (17.5%), paralysis (3.7%) and seizures (1.7%). In 29.7% of the patients, a neurological symptom was the initiating symptoms of the infection. Females were more likely to show headache and dizziness compared to males (p value<0.05). Headache intensity was also higher in females compared to males (p value<0.05). Headache prevalence was lower in older patients (p value<0.05), while memory loss and impaired consciousness were higher by increasing age (p values=0.002 and 0.001, respectively). CONCLUSION: Neurological manifestations were common among COVID-19 patients under study. Headache, as the most common neurological symptom among COVID-19 patients, was the most prevalent and intense among the female population. Headache, dizziness, sleeping problems, hyposmia/anosmia and hypogeusia were common COVID-19 neurological manifestations, while memory issues, auditory disturbances, paralysis, and seizures were less common.

Lessons learned from people with neurological diseases at the time of COVID-19: The EFNA-EAN survey.

BACKGROUND AND PURPOSE: The European Federation of Neurological Associations (EFNA), in partnership with the NeuroCOVID-19 taskforce of the European Academy of Neurology (EAN), has investigated the impact of the first wave of the COVID-19 pandemic on individuals with neurological diseases, as well as the hopes and fears of these patients about the post-pandemic phase. METHODS: An EFNA-EAN survey was available online to any person living with a neurological disorder in Europe. It consisted of 18 items concerning the impact of the first wave of the COVID-19 pandemic on the medical care of people with neurological disorders, and the hopes and fears of these individuals regarding the post-pandemic phase. RESULTS: For 44.4% of the 443 survey participants, the overall care of their neurological disease during the pandemic was inappropriate. This perception was mainly due to significant delays in accessing medical care (25.7%), insufficiently reliable information received about the potential impact of COVID-19 on their neurological disease (49.6%), and a substantial lack of involvement in their disease management decisions (54.3%). Participants indicated that their major concerns for the post-pandemic phase were experiencing longer waiting times to see a specialist (24.1%), suffering from social isolation and deteriorating mental well-being (23.1%), and facing delays in clinical trials with disinvestment in neuroscience research (13.1%). CONCLUSIONS: Despite the great efforts of health services to cope with the first wave of the COVID-19 pandemic, individuals with neurological conditions feel they have been left behind. These findings provide invaluable insights for improving the care of patients with neurological disorders in the further course of the COVID-19 pandemic.

The impact of COVID-19 pandemic on the utilization of ambulatory care for patients with chronic neurological diseases in Japan: Evaluation of an administrative claims database.

The COVID-19 pandemic has affected not only the emergency medical system, but also patients' regular ambulatory care, as such decrease in the number of patients visiting outpatient clinics decreased in 2020 than in 2019, or the ban lifting of subsequent visits by telephone for outpatient clinics since March 2020 in lieu of ambulatory care for chronic diseases. In this context, we investigate the impact of the COVID-19 pandemic on ambulatory care at Japanese outpatient clinics for patients with chronic neurological diseases during 2020. We collected data from the administrative claims database (DeSC database) covering more than 1 million individuals. Serial changes in the frequency of subsequent outpatient visits to clinics or hospitals (excluding large hospitals) for chronic ambulatory care of epilepsy, migraine, Parkinson's disease (PD), and Alzheimer's disease (AD) in 2020 were measured. As a result, since April 2020, the monthly outpatient visits for epilepsy, PD, and AD decreased slightly but significantly (approximately 0.90 in relative risk [RR]) but visits for migraine increased (RR = 1.15). Telephone visit was most frequently used in April-May, in less than 5% of monthly outpatient clinic visits for the examined neurological diseases. Outpatient visits for migraine treatment were more likely to be done by telephone than in case of other diseases (adjusted Odds ratio = 2.08). These results suggest that the impact of COVID-19 pandemic on regular ambulatory care for several chronic neurological diseases yielded different effect depending on the disease, in terms of the frequency or type of outpatient visits.

Neurological manifestations of COVID-19 in patients: from path physiology to therapy.

Coronavirus is a family of ARN positive single-stranded belonging to the family of Coronaviridae. There are several families of coronavirus that transmit more or less serious diseases. However, the so-called coronavirus-19 (SARS-CoV2) is the one that is currently causing most of the problems; in fact, biological dysfunctions that this virus causes provoke damage in various organs, from the lung to the heart, the kidney, the circulatory system, and even the brain. The neurological manifestations caused by viral infection, as well as the hypercoagulopathy and systemic inflammation, have been reported in several studies. In this review, we update the neurological mechanisms by which coronavirus-19 causes neurological manifestation in patients such as encephalomyelitis, Guillain-Barré syndrome, lacunars infarcts, neuropsychiatry disorders such as anxiety and depression, and vascular alterations. This review explains (a) the possible pathways by which coronavirus-19 can induce the different neurological manifestations, (b) the strategies used by the virus to cross the barrier system, (c) how the immune system responds to the infection, and (d) the treatment than can be administered to the COVID-19 patients.

Neurologic Manifestations of Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

PURPOSE OF REVIEW: This article describes the spectrum of neurologic complications associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, their underlying pathology and pathogenic mechanisms, gaps in knowledge, and current therapeutic strategies. RECENT FINDINGS: COVID-19 is the clinical syndrome caused by the novel coronavirus SARS-CoV-2. It can affect the entire neuraxis, and presentations in the acute phase are variable, although anosmia is a common manifestation. Encephalopathy is common in patients who are hospitalized and is often associated with multiorgan involvement. Immune-mediated encephalitis is probably underrecognized; however, viral encephalitis is rare. Other manifestations include stroke, seizures, myelitis, and peripheral neuropathies, including Guillain-Barré syndrome, which sometimes has atypical manifestations. Treatment is symptomatic, and immunotherapies have been used successfully in some patients. Long-term complications include dysautonomia, exercise intolerance, malaise, sleep disturbances, cognitive impairment, and mood disorders. SUMMARY: Neurologic manifestations of COVID-19 may occur in the acute setting and may be independent of respiratory manifestations. Immune-mediated syndromes and cerebrovascular complications are common. Large populations of patients are expected to have long-term neurologic complications of COVID-19, many of which may emerge only after recovery from the acute illness.