Anxiety and depression among epilepsy patients in low-risk areas for COVID-19 in the northern part of Guizhou Province, China, during the COVID-19 pandemic

BackgroundThis study was aimed to investigate whether patients with epilepsy (PWE) have higher depression and anxiety levels than the normal population in low-risk areas for coronavirus disease 2019 (COVID-19) in the northern part of Guizhou Province, China, during the COVID-19 epidemic, to evaluate their knowledge on COVID-19, and to analyze related factors for the psychological distress of PWE at this special time.MethodsThe survey was conducted online from February 28, 2020 to March 7, 2020 via a questionnaire. PWE from the outpatient clinic of epilepsy of the Affiliated Hospital of Zunyi Medical University, and healthy people matched for age and sex, participated in this study. Mental health was assessed via a generalized anxiety self-rating scale (GAD-7) and the self-rating depression scale (PHQ-9). The knowledge of COVID-19 in both groups was investigated.ResultsThere were no significant differences in the general demographics between the PWE and healthy control groups. The scores of PHQ-9 (P < 0.01) and GAD-7 (P < 0.001) were higher in the PWE group than in the healthy group. There was a significant difference in the proportions of respondents with different severities of depression and anxiety, between the two groups, which revealed significantly higher degree of depression and anxiety in PWE than in healthy people (P = 0, P = 0). Overwhelming awareness and stressful concerns for the pandemic and female patients with epilepsy were key factors that affect the level of anxiety and depression in PWE. Further, the PWE had less accurate knowledge of COVID-19 than healthy people (P < 0.001). There was no statistically significant difference between the two groups in the knowledge of virus transmission route, incubation period, susceptible population, transmission speed, clinical characteristics, and isolation measures on COVID-19 (P > 0.05). PWE knew less about some of the prevention and control measures of COVID-19 than healthy people.ConclusionsDuring the COVID-19 epidemic, excessive attention to the epidemic and the female sex are factors associated with anxiety and depression in PWE, even in low-risk areas.

Education on neuromuscular electrodiagnosis and neurological symptomatology

Neurological symptomatology is a crucial component of neurological expertise. The committee for fostering board-certified neurologists in the Japanese Society of Neurology (JSN) has hosted an educational activity for residents before the board examination, "The seminar for fostering board-certified neurologists" since 2004. In particular, the autumn seminar has been characterized by small group hands-on of neurological examinations and the evaluations of higher brain function. Besides this, hands-on seminar of neurological examinations by regional branches has been promoted by the JSN. In the Kanto Ko-shin-etsu branch, "The first hands-on seminar of neurological examinations" started in 2023 after a 3-year-suspension due to COVID-19. The most important educational activities in neuromuscular electrodiagnosis (EDx) is the "Neuromuscular diagnostics seminar" hosted since 2004 by the Japanese Society of Clinical Neurophysiology (JSCN). The majority of tutors and participants are neurologists. This seminar is also characterized by small-group, hands-on workshops. We have also run the overseas seminar, "Tokyo Super EMG hands-on," since 2013. These have undoubtedly contributed to enhancing the level of neuromuscular electrodiagnosis not only in Japan but also in other Asian countries. I have conducted studies on neurological symptomatology and neuromuscular electrodiagnosis, which are directly linked to enhancing clinical practice of neurologists through educational activities such as review articles or lectures. Due to the fact that symptomatology is crucial in neurological expertise, neurology is a basic specialty around the world except in Japan. In 2018, the JSN decided to aim to make neurology a basic specialty and continues to make efforts to attain this goal.Copyright © 2023 Japanese Society of Neurology and John Wiley & Sons Australia, Ltd.

RETROSPECTIVE STUDY OF VITAMIN D DEFICIENCY IN RHEUMATOLOGIC PATIENTS DURING THE COVID-19 PANDEMIC IN POLAND

BackgroundBefore the COVID-19 pandemic it was estimated that nearly 70% of the population is deficient in vitamin D - 25(OH)D <20ng/ml in Poland [1]. The percentage was expected to increase due to indoor isolation during the COVID-19 pandemic. Vitamin D has a positive effect on the condition of the bones, affects the course of autoimmune diseases, the course of neurological diseases, in type 2 diabetes, vitamin D supplementation improves glucose tolerance and reduces insulin resistance [2,3,4].ObjectivesThe aim of the retrospective study was to determine what percentage of rheumatology clinic patients suffer from vitamin D deficiency and whether this condition is effectively treated.MethodsIn January 2023, a retrospective analysis of the documentation of 172 patients treated at the Rheumatology Outpatient Clinic in Bełżyce (Poland) in 2022 was conducted.ResultsResults: The mean age of the 172 patients whose documentation was analyzed was 60.43 years (min 19, max 88). There were 132 women (76.8%) and 40 men (23.2%) in this group. The mean concentration of vitamin D was 25.57ng/ml±SD11.9 (min 5.7, max 75, Me 22.8). Vitamin D deficiency was found in 44% (serum concentration <20mg/ml), suboptimal concentration (20-30ng/ml) in 31%, optimal concentration (30-50ng/ml) in 21%, and high concentration (>50ng/ml) ml) in 4%. All those with a deficit or deficiency (75 people) were prescribed cholecalciferol in a dose of 20,000 units orally, 1 capsule twice a week after breakfast for 2 months [5]. Patients with optimal vitamin D levels were advised to take a dose of 2,000 units per day. Among the patients with deficit or deficiency, 48 people came for a follow-up visit to check the level of vitamin D (64% of the group with too low vitamin D concentration;28% of the entire group whose documentation was analyzed). In the follow-up examination, the mean concentration of vitamin D was 37.14±9.8ng/ml (min 28, max 84, Me 35.3). Therefore, a statistically significant increase in the concentration of vitamin D in the blood was noted (p<0.05). In the group of people who came for the follow-up examination, there were 35 women, whose mean age was 60.7 years and 13 men (mean age 68.2 years).Conclusion:1. During the COVID-19 pandemic in the group of outpatient rheumatology patients, 75% had a deficiency or suboptimal level of vitamin D.2. Treatment with cholecalciferol in a dose of 20,000 IU twice a week orally for 2 months is effective treatment of vitamin D deficiency.3. Too low percentage of patients diagnosed with vitamin D deficiency come for visits and check-ups.References[1]Hilger J., Friedel A., Herr R.. A systematic review of vitamin D status in populations worldwide. Br J Nutr. 2013;9: 1023.[2]Karczmarewicz E., Czekuć-Kryskiewicz E., Płudowski P. Effect of vitamin D status on pharmacological treatment efficiency-impact on cost- effective management in medicine. Dermatoendocrinology, 2013;5: 299-304.[3]Zhu J., Bing C., Wilding J.P.H. Vitamin d receptor ligands attenuate the inflammatory profile of IL-1β-stimulated human white preadipocytes via modulating the NF-κB and unfolded protein response pathways Biochemical and Biophysical Research Communications 2-18, 503: 1049-1056.[4]Luan W., Hammond L.A. Vuillermot S. Maternal vitamin d prevents abnormal dopaminergic development and function in a mouse model of prenatal immune activation. Scientific Reports 2018;8 (1) article numer 9741.[5]Płudowski P., Karczmarewicz E. i wsp. Witamina D: Rekomendacje dawkowania w populacji osób zdrowych oraz w grupach ryzyka deficytów.Wytyczne dla Europy Środkowej 2013 r. Standardy Medyczne/Pediatria 2013, 10, 573-578 (in Polish).Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Immunogenetic landscape of COVID-19 infections related neurological complications

The human leukocyte antigen (HLA) is a critical component of antigen presentation and plays crucial role in conferring differential susceptibility and severity of diseases caused by viruses such as COVID-19. The immunogenetic profile of populations, BCG vaccination status, and a host of lifestyle factors might contribute to the observed variations in mortality rates due to COVID-19. These genetic, epigenetic, and environmental factors could widely influence infection dynamics and immune responses against COVID-19. The aim of this review is to provide an update on HLA association with SARS-CoV-2 infection in global populations and to highlight the possible neurological involvements. We also set out to explore the HLA immunogenetic markers related to COVID‐19 infections that can be used in screening high‐risk individuals for personalized therapies and in community-based vaccine development. © 2023 Elsevier Inc. All rights reserved.

Relationship between neurological manifestations and severity of COVID-19. San Vicente de Paul Hospital. Ecuador 2021.

Introduction: SARS-CoV-2 mainly affects the respiratory system, but the damage caused by this virus also extends to other systems, including the nervous system, and the mechanisms of neurological infection can be direct or indirect. Objective(s): To determine the relationship between neurological manifestations and disease severity in symptomatic COVID-19 positive patients at San Vicente de Paul Hospital in 2021. Material(s) and Method(s): A cross-sectional observational study was conducted using medical records of patients hospitalized with COVID-19 and neurological manifestations, which were classified into manifestations of the central nervous system and manifestations of the peripheral nervous system. Result(s): The results show that 74,1 % of patients presented neurological manifestations;the highest percentage was concentrated in patients who developed severe disease (15 [60 %], CNS;91 [77,1 %], PNS;125 [65,4 %], CNS and PNS). The joint presence of central and peripheral neurological manifestations was significantly associated with critical COVID-19 (P value= 0,011;OR: 2,005). The mortality rate reached 2,69 %. Conclusion(s): Neurological manifestations in hospitalized COVID-19 patients are very common, and critical COVID-19 is more likely to have neurological manifestations.Copyright © 2022 Universidad de Ciencias Medicas de La Hab. All rights reserved.

Once again about the new coronavirus infection COVID-19.

The COVID-19 pandemic continues to affect millions of people with increasing morbidity and mortality. Substantial variations exists in drug treatment of COVID-19. Extracorporeal membrane oxygenation (ECMO) facilitates survival of select critically ill patients with COVID-19 with about 25-45% survival rate;survivors tend to be younger and have a shorter duration from diagnosis to cannulation. The practioners found the severe complications including concomitant neurological manifestations (from headache, anosmia, ageusia to encephalopathy, stroke and others) and multisystem inflammation syndrome (MIS) predominantly in children few weeks after SARS-CoV-2 infection and characterized by persistent fever, vomiting, headache, Kawasaki - like rash and fatigue. Regarding MIS the authors did not find strong association between the complications rate and outcomes and regime of immunomodulation treatment. The neurological manifestations in pts with COVID-19 were associated with higher in-hospital mortality.Copyright © 2022 Sinergia Press. All rights reserved.

Long-Term Neurologic Sequelae Among Patients with Varying COVID-19 Severity: An Administrative Claims Database Analysis

Objectives: Examine the long-term incident neurologic sequelae post COVID recovery and assess relationship with COVID severity using real-world data. Method(s): This retrospective cohort study was conducted using Optum Research Database between 01July2019 to 30Sep2022. Patients included were >=18 years with COVID diagnosis (index date) between 01Jan2020 and 31Oct2020, with continuous enrollment 6 months before and >=12 months after index date, known demographics, not pregnant, and with no baseline neurologic conditions. Patients were stratified into COVID severity cohorts as mild (index diagnosis), moderate (inpatient visit within 15 days of index), or severe (evidence of acute respiratory distress) and followed for a minimum of 12-months post-index. Neurologic sequelae examined were persistent headache, migraine, anosmia, sleep disturbance, cognitive dysfunction, post-traumatic stress disorder, suicidality, anxiety, depression, attention deficit hyperactivity disorder, cerebrovascular disease (CVD), fatigue/myalgia and tremors. Descriptive statistics and incidence rate ratios (IRR) were calculated to assess outcomes. Result(s): Of 534,843 patients, 107,656 (Mild 96,637;Moderate 3,371;Severe 7,648) met the study inclusion criteria. Median follow up time was 750, 774 and 768 days in the mild, moderate and severe cohorts, respectively. About 20% of patients in the mild, 32% in moderate and 35% in the severe cohort experienced >=3 neurologic sequelae during the follow-up period. A significantly higher incidence of any neurologic sequelae was observed in moderate and severe cohorts compared with the mild cohort (IRR 3.1 and 3.0, respectively;p<0.001). Cognitive dysfunction (moderate IRR 5.4, severe IRR 5.7;p<0.001), and CVD (moderate IRR 4.8, severe IRR 4.0;p<0.001) were the most commonly occurring manifestations in moderate and severe cohorts compared with the mild cohort. Conclusion(s): These results highlight the need for long-term monitoring and preventative strategies for neurologic conditions post COVID recovery that might impair quality of life and increase overall healthcare burden in the U.S.Copyright © 2023

TL,DR - Improving handover through the use of an integrated electronic discharge proforma in neurocritical care

Introduction: Effective handover between treating clinical teams is an important part of communication in the care of patients leaving the intensive care environment.1 This can be even more vital in neurocritical care, where patients may be unable to communicate their own history due to neurological deficits and whose families are unable to visit due to COVID. These patients often have had complex neurosurgical interventions and ongoing complex MDT discussion due to the nature of their illness. Handover needs to represent this. Furthermore, as a specialist tertiary centre, many patients leave the unit as repatriations to other intensive care units. In these situations, it is even more important for good handover to contain the relevant and succinct information for ongoing care. Objective(s): We aim to improve the quality of handover from the intensive care team to ward teams at a specialist neurocritical care centre through the use of an electronic discharge proforma integrated into the electronic patient record (EpicCare Epic Systems Corporation). This is a system that has only recently been introduced locally and has required modification for the intensive care environment. Method(s): We performed a retrospective cohort study of documented transfer of care (TOC) summaries for patients entering the ICU in a month-long period. 67 patient admissions were identified as possible candidates with 11 cases excluded as not meeting criteria. The TOC summaries of suitable cases were compared to standards set by the Faculty of Intensive Care Medicine and Intensive Care Society and criteria tailored to the neuro-intensive care environment. Following this, we implemented a curated discharge proforma for all patients leaving intensive care. Through the use of smart lists and specific prompts, we aim to improve compliance with the guidelines and improve the quality of TOC. The project is currently ongoing and we aim to repeat the analysis in March 2022 to review if there has been improved compliance. Result(s): Compliance for the first round of discharges was variable. There was generally good quality information on the summary of stay of the patient (96%) and ongoing plan for the care of the patient (88%). However, documentation of the rehabilitation needs (32%), psychological needs (14%), communication needs (16%), safeguarding issues (4%), and resuscitation and escalation status of the patient was suboptimal (4%). Documentation of verbal handover to the parent team (25%) and critical care outreach team (45%) was mixed. Conclusion(s): Here we present the use of an electronic discharge proforma to improve the quality of handover in patients leaving the intensive care environment. While the study is ongoing, we show that currently local patient handover is often incomplete with a lack of detail in the TOC summary and poor verbal communication between teams. Through the use of this proforma, we aim to improve the quality of this handover and improve the continuity of care for patients leaving the neuro-intensive care unit.

Long-COVID and its Physical and Neurological Symptoms in Adults: A Systematic Review

This review was carried out with the objective to study patterns of neurological, psychological and other physical consequences of COVID-19 in the long term. The guidelines of PRISMA (Preferred Reporting Items for Systematic Reviews and Metaanalyses) had been followed;22 articles, published during January 2020 to September 2021, were selected. Original research, review articles, editorial and viewpoints were included. Google Scholar, Medline, and PubMed were searched through 2020 till 2021.Data collection in selected studies was performed mainly through the online survey, telephone survey, use of medical records, and patient interviews. This systematic review contains the studies conducted in the American, Asian and European countries. The major outcomes identified were the neurological, psychological, and other long-term chronic manifestations of COVID- 19. This review demonstrates that long-COVID has started to bring a huge wave of patients, the count of them being millions now, who can enter a phase of disability due to neurological damages if not treated during the early course of illness. Though more disabling than lethal, long-COVID patients with a neurological deficit is expected to overburden the healthcare system globally which is already been struggling to handle acute COVID-19 patients in this once-in-a-lifetime pandemic.Copyright © 2023 Lahore Medical And Dental College. All rights reserved.

Bell Palsy Incidence in Patients with Post-COVID: A Retrospective Study

Bell palsy is caused by impaired functioning of the 7th cranial nerve. A disparity in the stable state of the cytokine regulatory axis and a cytokine storm are observed to occur from the binding of the ACE2 to the COVID, and the subsequent functional alterations in the ACE2/AT2R suggest that COVID-19 may use direct or indirect processes to produce neurological symptoms. Increased cases of Bell palsy were reported during the CoV pandemic, so our study aimed to estimate the incidence rate of Bell palsy among COVID-19 patients in South Bangalore, India. Secondary data of patients with Bell palsy were obtained retrospectively from two multispecialty Hospitals in South Bangalore. COVID positive populations were collected between the period of March 2021 and February 2022, and many Bell palsy cases within 3 months of post-Covid period were included. Confirmatory calls were made for patients with Covid Positive who were not diagnosed to discover the occurrence of Bell palsy. A retrospective analysis of Bell palsy cases found 11 incidences between March 2021 and February 2022, when there were 1577 COVID patients in total. According to descriptive statistical analysis, the prevalence of Bell palsy increased by 0.7% during the COVID-19 pandemic. Bell palsy could be considered one of the neurological complications among COVID-19 patients, and appropriate preventative measures should be taken.Copyright © 2023 International Journal of Nutrition, Pharmacology, Neurological Diseases Published by Wolters Kluwer - Medknow.

Global analysis of lysine acetylation in the brain cortex of K18-hACE2 mice infected with SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected hundreds of millions of people all over the world and thus threatens human life. Clinical evidence shows that SARS-CoV-2 infection can cause several neurological consequences, but the existing antiviral drugs and vaccines have failed to stop its spread. Therefore, an understanding of the response to SARS-CoV-2 infection of hosts is vital to find a resultful therapy. Here, we employed a K18-hACE2 mouse infection model and LC-MS/MS to systematically evaluate the acetylomes of brain cortexes in the presence and absence of SARS-CoV-2 infection. Using a label-free strategy, 3829 lysine acetylation (Kac) sites in 1735 histone and nonhistone proteins were identified. Bioinformatics analyses indicated that SARS-CoV-2 infection might lead to neurological consequences via acetylation or deacetylation of important proteins. According to a previous study, we found 26 SARS-CoV-2 proteins interacted with 61 differentially expressed acetylated proteins with high confidence and identified one acetylated SARS-CoV-2 protein nucleocapsid phosphoprotein. We greatly expanded the known set of acetylated proteins and provide the first report of the brain cortex acetylome in this model and thus a theoretical basis for future research on the pathological mechanisms and therapies of neurological consequences after SARS-CoV-2 infection.

Therapeutic prospects of naturally occurring p38 MAPK inhibitors tanshinone IIA and pinocembrin for the treatment of SARS-CoV-2-induced CNS complications.

P38 mitogen-activated protein kinase (p38 MAPK) signaling pathway is closely related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) replication and hyperinflammatory responses in coronavirus disease 2019 (COVID-19). Therefore, blood-brain barrier-penetrating p38 MAPK inhibitors have good potential for the treatment of central nervous system (CNS) complications of COVID-19. The aim of the present study is the characterization of the therapeutic potential of tanshinone IIA and pinocembrin for the treatment of CNS complications of COVID-19. Studies published in high-quality journals indexed in databases Scopus, Web of Science, PubMed, and so forth were used to review the therapeutic capabilities of selected compounds. In continuation of our previous efforts to identify agents with favorable activity/toxicity profiles for the treatment of COVID-19, tanshinone IIA and pinocembrin were identified with a high ability to penetrate the CNS. Considering the nature of the study, no specific time frame was determined for the selection of studies, but the focus was strongly on studies published after the emergence of COVID-19. By describing the association of COVID-19-induced CNS disorders with p38 MAPK pathway disruption, this study concludes that tanshinone IIA and pinocembrin have great potential for better treatment of these complications. The inclusion of these compounds in the drug regimen of COVID-19 patients requires confirmation of their effectiveness through the conduction of high-quality clinical trials.

Serious neurological adverse events following immunization against SARS-CoV-2: a narrative review of the literature.

Amid the coronavirus disease 2019 (COVID-19) pandemic, massive immunization campaigns became the most promising public health measure. During clinical trials, certain neurological adverse effects following immunization (AEFIs) were observed; however, acceptable safety profiles lead to emergency authorization for the distribution and use of the vaccines. To contribute to pharmacovigilance and lessen the potential negative impact that vaccine hesitancy would have on immunization programs, we conducted a review of the scientific literature concerning the epidemiological data, clinical presentation, and potential mechanisms of these neurological AEFIs. There is some epidemiological evidence linking COVID-19 vaccines to cerebral venous sinus thrombosis, arterial ischemic stroke, convulsive disorder, Guillain-Barré syndrome, facial nerve palsy, and other neurological conditions. Cerebral venous sinus thrombosis has been associated with a thrombotic thrombocytopenia induced by the vaccine, similar to that induced by heparin, which suggests similar pathogenic mechanisms (likely involving antibodies against platelet factor 4, a chemokine released from activated platelets). Arterial ischemic stroke is another thrombotic condition observed among some COVID-19 vaccine recipients. Vaccine-induced convulsive disorder might be the result of structural abnormalities potentially caused by the vaccine or autoimmune mechanisms. Guillain-Barré syndrome and facial nerve palsy may also be linked to the immunization event, possibly due to immune mechanisms such as uncontrolled cytokine release, autoantibody production, or bystander effect. However, these events are mostly uncommon and the evidence for the association with the vaccine is not conclusive. Furthermore, the potential pathophysiological mechanisms remain largely unknown. Nevertheless, neurological AEFIs can be serious, life-threatening or even fatal. In sum, COVID-19 vaccines are generally safe and the risk of neurological AEFIs does not outweigh the benefits of immunization. However, early diagnosis and treatment of neurological AEFIs are of utmost importance, and both health professionals and the public should be aware of these conditions.

A review of undesired effects involving the nervous system following the administration of COVID-19 vaccines Among the range of complications that can occur after a vaccine, some of them can affect the nervous system and its vasculature. This narrative review aims to evaluate some serious neurological conditions following COVID-19 vaccination. We searched biomedical journal databases where physicians around the globe reported different complications after the administration of different COVID-19 vaccines. Besides reports of cases in individual patients or small groups, we reviewed studies that included bigger groups of patients (e.g. vaccinated versus non-vaccinated) and compared the occurrence of these events between them. We found that after the administration of a certain type of vaccine (e.g. ChAdOx1-S/Oxford, AstraZeneca vaccine), serious neurological complications were rare, with abnormal clot formation involving cerebral blood vessels being one of the most important among them. Nonetheless, other conditions have been observed after the administration of the vaccines; however, it is not certain yet if the vaccines are the actual cause of these complications. There are some hypotheses that could explain why these adverse reactions take place after a vaccine. For instance, an abnormal immune response to the vaccine leads to the production of antibodies (i.e. proteins made by the immune system in response to the presence of a foreign substance). These antibodies trigger a response that could eventually result in clot formation. Besides, the immune response can also produce other adverse effects, including convulsive disorder, Guillain­Barré syndrome, and facial nerve palsy. Scientific evidence suggests that vaccines are safe overall. While mild complications, such as pain at the site of injection or bruising might occur, more serious events remain rare. Furthermore, the complications derived from COVID-19 are far more likely in non-vaccinated individuals than the complications associated with the vaccine. Thus, vaccination continues to be the safest and most effective strategy to control the ongoing pandemic. However, both health professionals and the public should be aware of the possibility of serious neurological adverse reactions occurring after vaccination to allow early diagnosis and treatment.

The complex syndrome of functional neurological disorder.

BACKGROUND: Patients with functional neurological disorders (FND) often present with multiple motor, sensory, psychological and cognitive symptoms. In order to explore the relationship between these common symptoms, we performed a detailed clinical assessment of motor, non-motor symptoms, health-related quality of life (HRQoL) and disability in a large cohort of patients with motor FND. To understand the clinical heterogeneity, cluster analysis was used to search for subgroups within the cohort. METHODS: One hundred fifty-two patients with a clinically established diagnosis of motor FND were assessed for motor symptom severity using the Simplified Functional Movement Disorder Rating Scale (S-FMDRS), the number of different motor phenotypes (i.e. tremor, dystonia, gait disorder, myoclonus, and weakness), gait severity and postural instability. All patients then evaluated each motor symptom type severity on a Likert scale and completed questionnaires for depression, anxiety, pain, fatigue, cognitive complaints and HRQoL. RESULTS: Significant correlations were found among the self-reported and all objective motor symptoms severity measures. All self-reported measures including HRQoL correlated strongly with each other. S-FMDRS weakly correlated with HRQoL. Hierarchical cluster analysis supplemented with gap statistics revealed a homogenous patient sample which could not be separated into subgroups. CONCLUSIONS: We interpret the lack of evidence of clusters along with a high degree of correlation between all self-reported and objective measures of motor or non-motor symptoms and HRQoL within current neurobiological models as evidence to support a unified pathophysiology of 'functional' symptoms. Our results support the unification of functional and somatic syndromes in classification schemes and for future mechanistic and therapeutic research.

Review of Neurological Manifestations of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect any part of the neuraxis. Many neurological conditions have been attributed to be caused by SARS-CoV-2, namely encephalopathy (acute necrotizing encephalopathy and encephalopathy with reversible splenial lesions), seizures, stroke, cranial nerve palsies, meningoencephalitis, acute disseminated encephalomyelitis (ADEM), transverse myelitis (long and short segment), Guillain-Barré syndrome (GBS) and its variants, polyneuritis cranialis, optic neuritis (ON), plexopathy, myasthenia gravis (MG), and myositis. The pathophysiology differs depending on the time frame of presentation. In patients with concomitant pulmonary disease, for instance, acute neurological illness appears to be caused by endotheliopathy and cytokine storm. Autoimmunity and molecular mimicry are causative for post-coronavirus disease 2019 (COVID-19)-sequelae. It has not yet been shown that the virus can penetrate the central nervous system (CNS) directly. This review aims to describe the disease and root pathogenic cause of the various neurological manifestations of COVID-19. We searched Pubmed/Medline and Google Scholar using the keywords "SARS-CoV-2" and "neurological illness" for articles published between January 2020 and November 2022. Then, we used the SWIFT-Review (Sciome LLC, North Carolina, United States), a text-mining workbench for systematic review, to classify the 1383 articles into MeSH hierarchical tree codes for articles on various parts of the nervous system, such as the CNS, peripheral nervous system, autonomic nervous system, neuromuscular junction, sensory system, and musculoskeletal system. Finally, we reviewed 152 articles in full text. SARS-CoV-2 RNA has been found in multiple brain areas without any histopathological changes. Despite the absence of in vivo virions or virus-infected cells, CNS inflammation has been reported, especially in the olfactory bulb and brain stem. SARS-CoV-2 genomes and proteins have been found in affected individuals' brain tissues, but corresponding neuropathologic changes are seldom found in these cases. Additionally, viral RNA can rarely be identified in neurological patients' CSF post hoc SARS-CoV-2 infection. Most patients with neurological symptoms do not have active viral replication in the nervous system and infrequently have typical clinical and laboratory characteristics of viral CNS infections. Endotheliopathy and the systemic inflammatory response to SARS-CoV-2 infection play a crucial role in developing neuro-COVID-19, with proinflammatory cytokine release mediating both pathological pathways. The systemic inflammatory mediators likely activate astrocytes and microglia across the blood-brain barrier, indirectly affecting CNS-specific immune activation and tissue injury. The management differs according to co-morbidities and the neurological disorder.

SARS-CoV-2 and the nervous system: current perspectives.

SARS-CoV-2 infection frequently causes neurological impairment in both adults and children. Recent publications have described significant aspects of the viral pathophysiology associated with neurological dysfunction. In theory, neurological manifestations following SARS-CoV-2 infection may be caused directly by the effects of the virus infecting the brain or indirectly by the local and systemic immune responses against the virus. Neurological manifestations can occur during the acute phase as well as in the post-acute phase of the infection. In this review, we discuss recent literature describing the association of nervous system disorders with COVID-19.

Case report: Unusual patient with dermatomyositis associated with SARS-CoV-2 infection.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak is a major challenge for clinicians. SARS-CoV-2 infection results in coronavirus disease 2019 (COVID-19), and it is best known for its respiratory symptoms. It can also result in several extrapulmonary manifestations such as neurological complications potentially experienced during the course of COVID-19. The association of dermatomyositis (DM) with COVID-19 pathogenesis has not been well-studied. This study aimed to present a previously healthy 37-year-old man, a soldier by profession, with symptoms of DM on the 4th day from the onset of COVID-19. The patient presented DM symptoms with both skin and muscle manifestations. The patient suffered from cough, fever, and fatigue to begin with, and reverse-transcription polymerase chain reaction (RT-PCR) reported positive for SARS-CoV-2 infection. The laboratory findings showed, intra alia, elevated muscle enzymes CK 8253 U/l (N: <145 U/l), a positive test for myositis-specific autoantibodies (anti-Mi-2), electrodiagnostic tests exhibited features of myopathy, with the presence of muscle and skin symptoms. The patient improved with corticosteroids and immunosuppressive agent therapy. In summary, the association between COVID-19 and the development of multi-system autoimmune disorders such as DM remains unclear. Nevertheless, viral infections such as SARS-CoV-2 may likely serve as a trigger.

Seronegative acute encephalitis following COVID-19 vaccines: a case series of an overlooked diagnosis with literature review.

PURPOSE: Autoimmune encephalitis is a neurological emergency of new-onset altered mental status, caused by an exaggerated immune-mediated response that targets the central nervous system. Autoimmune encephalitis has become an emerging differential diagnosis, when a classical infection cannot explain neurological symptoms. Displaying overlapping clinical presentations, ranging from the insidious onset of cognitive deficiency to more severe forms of encephalopathy with refractory seizures, autoimmune encephalitis can be challenging for clinicians. When evidence of malignancy is absent and pathogenic autoantibodies are undetected, with typical clinical and imaging features of autoimmune encephalitis, seronegative autoimmune encephalitis may be considered. Recently, vaccination-related autoimmune encephalitis and acute encephalitis after COVID-19 vaccination have attracted attention. METHODS AND RESULTS: We report a case series consisting of three patients with autoimmune encephalitis occurring shortly after COVID-19 vaccination and a current review of all previous reported autoimmune encephalitis related to COVID-19 vaccines. CONCLUSION: We emphasise on the prompt diagnosis of autoimmune encephalitis induced by Covid-19 vaccines and its timely treatment to improve the clinical outcome of this severe neurological condition. Post-licencing vaccine safety surveillance for potential adverse events is essential for vaccine safety and public confidence.

Neurological manifestations of COVID-19 in pregnancy: a cross-sectional study.

The occurrence of neurological manifestations and complications in pregnant women compared to non-pregnant women with COVID-19 is unclear. This cross-sectional study included women aged over 18 years hospitalized with SARS-CoV-2 infection confirmed by RT-PCR from March to June 2020 in Recife, Brazil. We evaluated 360 women, including 82 pregnant patients who were significantly younger (27.5 vs. 53.6 years; p < 0.01) and less frequently obese (2.4% vs. 15.1%; p < 0.01) than the non-pregnant group. All pregnancies were confirmed using ultrasound imaging. Abdominal pain was the only more frequent COVID-19 manifestation during pregnancy (23.2% vs. 6.8%; p < 0.01), but was not associated with the outcomes. Almost half the pregnant women presented neurological manifestations, including anosmia (31.7%), headache (25.6%), ageusia (17.1%), and fatigue (12.2%). However, neurological manifestations occurred similarly in pregnant and non-pregnant women. Four (4.9%) pregnant women and 64 non-pregnant women (23%) presented delirium, but the frequency with age-adjustment was similar in the non-pregnant group. Pregnant women with COVID and preeclampsia (19.5%) or eclampsia (3.7%) were older (31.8 vs. 26.5 years; p < 0.01), and epileptic seizures occurred more often in association with eclampsia (18.8% vs. 1.5%; p < 0.01) regardless of previous epilepsy. There were three maternal deaths (3.7%), one dead fetus, and one miscarriage. The overall prognosis was good. There was no difference in prolonged hospital stay, the need for ICU and mechanical ventilation, or death when comparing pregnant and non-pregnant women.

Reported neurological symptoms after severe acute respiratory syndrome coronavirus type 2 infection: A systematic diagnostic approach.

BACKGROUND AND PURPOSE: Following increasing demands of patients with suspected neurological symptoms after infection with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the Department of Neurology at the Medical University of Vienna established a new outpatient clinic to systematically assess, diagnose, and document neurological complaints potentially associated with a prior SARS-CoV-2 infection. METHODS: The data presented here include prospectively collected 156 outpatients from May 2021 to April 2022. Patients underwent semistandardized interviewing about symptoms with reported onset after SARS-CoV-2 infection, neurological examination, and comprehensive diagnostic workup. RESULTS: Reported new onset symptoms after infection included fatigue (77.6%), subjective cognitive impairment (72.4%), headache (47.7%), loss of smell and/or taste (43.2%), and sleep disturbances (42.2%). Most patients had a mild coronavirus disease (COVID-19) disease course (84%) and reported comorbidities (71%), of which the most frequent were psychiatric disorders (34%). Frequency of symptoms was not associated with age, sex, or severity of COVID-19 course. A comprehensive diagnostic workup revealed no neurological abnormalities in the clinical examination, or electrophysiological or imaging assessments in the majority of patients (n = 143, 91.7%). Neuropsychological assessment of a subgroup of patients (n = 28, 17.9%) showed that cognitive impairments in executive functions and attention, anxiety, depression, and somatization symptoms were highly common. CONCLUSIONS: In this systematic registry, we identified fatigue, cognitive impairment, and headache as the most frequently reported persisting complaints after SARS-CoV-2 infection. Structural neurological findings were rare. We also suspect a link between the growing burden of the COVID-19 pandemic on personal lives and the increase in reported neurological and psychiatric complaints.