Blood-borne viruses and neurological manifestations: An overview.

Infections caused by blood-borne viruses, such as human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV), hepatitis C virus (HCV), and hepatitis B virus (HBV), are systemic diseases that can lead to a wide range of pathological manifestations. Besides causing severe immune and hepatic disorders, these viral pathogens can also induce neurological dysfunctions via both direct and indirect mechanisms. Neurological dysfunctions are one of the most common manifestations caused by these viruses that can also serve as indicators of their infection, impacting the clinical presentation of the disease. The main neurological manifestations of these blood-borne viral pathogens consist of several central and peripheral nervous system (CNS and PNS, respectively) dysfunctions. The most common neurological manifestations of HIV, HTLV, HCV, and HBV include HIV-associated peripheral neuropathy (PN), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and HCV-/HBV-associated PN, respectively. Nonetheless, patients infected with these viruses may experience other neurological disorders, either associated with these conditions or manifesting in isolation, which can often go unnoticed or undiagnosed by physicians. The present review aims to provide an overview of the latest evidence on the relationship between blood-borne viruses and neurological disorders to highlight neurological conditions that may be somewhat overlooked by mainstream literature and physicians.

Targeting the mammalian target of rapamycin pathway in neurological manifestations of Covid-19.

The diverse and severe nature of neurological manifestations associated with coronavirus disease 2019 (Covid-19) has garnered increasing attention. Exploring the potential to decrease neurological complications in Covid-19 patients involves targeting the mammalian target of rapamycin (mTOR) pathway as a therapeutic strategy. The mTOR pathway, widely recognised for its central role in essential cellular processes like synthesising proteins, facilitating autophagy, and modulating immune responses, has implications in various neurological disorders. Drawing parallels between these disorders and the observed neurological complications in Covid-19, we present a comprehensive review on the current understanding of mTOR signalling in the context of severe acute respiratory syndrome coronavirus 2 infection and neuroinflammation.

Neurological manifestations of Flaviviridae, Togaviridae, and Peribunyaviridae as vector-borne viruses.

Vector-borne viruses pose a significant health problem worldwide, as they are transmitted to humans through the bite of infected arthropods such as mosquitoes and ticks. In recent years, emerging and re-emerging vector-borne diseases have gained attention as they can cause a wide spectrum of neurological manifestations. The neurological manifestations of vector-borne viruses encompass a board spectrum of clinical manifestations, ranging from mild and self-limiting symptoms to severe and life-threatening conditions. Common neurological complications include viral encephalitis, acute flaccid paralysis, aseptic meningitis, and various neuromuscular disorders. The specific viruses responsible for these neurological sequelae vary by geographic region and include Orthoflavivirus nilense, Zika virus, dengue virus, chikungunya virus, Japanese encephalitis virus, and tick-borne encephalitis virus. This review focuses on the pathogenesis of these neurologic complications and highlights the mechanisms by which vector-borne viruses invade the central nervous system and trigger neuroinflammatory responses. Diagnostic challenges and strategies for early detection of neurological manifestations are discussed, emphasising the importance of clinical suspicion and advanced laboratory testing.

Dengue virus infection and neurological manifestations: an update.

Dengue virus is a flavivirus transmitted by the mosquitoes, Aedes aegypti and Aedes albopictus. Dengue infection by all four serotypes (DEN 1 to 4) is endemic globally in regions with tropical and subtropical climates, with an estimated 100-400 million infections annually. Among those hospitalized, the mortality is about 1%. Neurological involvement has been reported to be about 5%. The spectrum of neurological manifestations spans both the peripheral and central nervous systems. These manifestations could possibly be categorized into those directly related to dengue infection, i.e. acute and chronic encephalitis, indirect complications leading to dengue encephalopathy, and post-infectious syndrome due to immune-mediated reactions, and manifestations with uncertain mechanisms, such as acute transverse myelitis, acute cerebellitis and myositis. The rising trend in global dengue incidence calls for attention to a more explicit definition of each neurological manifestation for more accurate epidemiological data. The actual global burden of dengue infection with neurological manifestation is essential for future planning and execution of strategies, especially in the development of effective antivirals and vaccines against the dengue virus. In this article, we discuss the recent findings of different spectrums of neurological manifestations in dengue infection and provide an update on antiviral and vaccine development and their challenges.

Aberrant copper metabolism and hepatic inflammation cause neurological manifestations in a mouse model of Wilson's disease.

Pathogenic germline mutations in the P-type copper-transporting ATPase (ATP7B) gene cause Wilson's disease (WD), a hereditary disorder characterized by disrupted copper metabolism. The Arg778Leu (R778L) mutation in exon 8 is prevalent among individuals with WD in East Asia and is associated with more severe phenotypes. In this study, we generated a WD mouse model harboring R778L mutation (R778L mice) using CRISPR/Cas9. R778L mice exhibit a range of pathological characteristics resembling those of patients with WD and the same point mutations, including aberrant copper metabolism, pathological cellular injury, inflammation, and severe hepatic fibrosis. At 3-5 months of age, these mice started to display neurological deficits in motor coordination and cognitive dysfunction, accompanied by increased expression of inflammatory cytokines in the central nervous system. Microglia in the striatum and cortex exhibit significant activation, shorter processes, and decreased branch points. However, the Cu2+ levels in the brain tissue of R778L mice did not differ significantly from those of wild-type mice. Notably, inhibition of hepatic inflammation with PJ34 or siNfkb markedly alleviated the deficiencies in cognitive performance and improved locomotor activity in R778L mice. Thus, this study establishes a novel murine model to investigate the pathophysiology of WD, highlights the liver-brain crosstalk responsible for neurological manifestations in individuals with WD caused by the R778L point mutation, and demonstrates the potential of modulating liver inflammation as a therapeutic strategy for alleviating the neurological manifestations of WD.

Diagnostic value of anti-VZV IgG in neurological diseases among varicella unvaccinated individuals.

Varicella zoster virus (VZV) is a neurotropic alphaherpesvirus that causes neurological manifestations either as a complication of primary infection or reactivation. VZV induced neurological diseases have a good prognosis when confirmed early and treated with anti-viral therapy. Myelitis, encephalitis, ventriculitis or meningitis can occur without a telltale rash in immunocompetent and immunocompromised individuals making the diagnosis difficult. We analyzed CSF and serum samples from 30 unvaccinated study participants (17 male and 13 female) to determine the presence of VZV DNA by PCR in CSF and to estimate serum and CSF anti-VZV IgG and albumin levels in participants with neurological manifestations with/without rash. Anti-VZV IgG was detected in CSF (n = 22, [73%]) and serum (n = 29, [97%]) of pediatric and adult participants. Anti-VZV IgG were detected in CSF of participants with varied clinical presentation altered sensorium (n = 8, [36%]), meningitis (n = 4, [18%]), acute febrile illness (n = 3, [14%], encephalopathy/meningoencephalitis (n = 2, [9%]), irritability (n = 2, [9%]) and each patient from cerebrovascular stroke, demyelinating disorder and febrile seizure (n = 1, [4.5%]). VZV DNA was detected from one participant and CSF serum albumin levels were elevated in 53% of study participants. VZV DNA is present up to 1-2 weeks post onset of disease, after which anti-VZV antibody may be the only indicator of disease and therefore both VZV DNA and anti-VZV IgG need to be tested for in CSF. As VZV DNA and VZV IgG antibody are both good indicators of VZV reactivation, routine testing would result in reduced morbidity and mortality by early detection of disease and antiviral treatment.

Prevalence and Trajectories of Post-COVID-19 Neurological Manifestations: A Systematic Review and Meta-Analysis.

INTRODUCTION: The aim of this systematic review and meta-analysis was to evaluate the prevalence of thirteen neurological manifestations in people affected by COVID-19 during the acute phase and at 3, 6, 9 and 12-month follow-up time points. METHODS: The study protocol was registered with PROSPERO (CRD42022325505). MEDLINE (PubMed), Embase, and the Cochrane Library were used as information sources. Eligible studies included original articles of cohort studies, case-control studies, cross-sectional studies, and case series with ≥5 subjects that reported the prevalence and type of neurological manifestations, with a minimum follow-up of 3 months after the acute phase of COVID-19 disease. Two independent reviewers screened studies from January 1, 2020, to June 16, 2022. The following manifestations were assessed: neuromuscular disorders, encephalopathy/altered mental status/delirium, movement disorders, dysautonomia, cerebrovascular disorders, cognitive impairment/dementia, sleep disorders, seizures, syncope/transient loss of consciousness, fatigue, gait disturbances, anosmia/hyposmia, and headache. The pooled prevalence and their 95% confidence intervals were calculated at the six pre-specified times. RESULTS: 126 of 6,565 screened studies fulfilled the eligibility criteria, accounting for 1,542,300 subjects with COVID-19 disease. Of these, four studies only reported data on neurological conditions other than the 13 selected. The neurological disorders with the highest pooled prevalence estimates (per 100 subjects) during the acute phase of COVID-19 were anosmia/hyposmia, fatigue, headache, encephalopathy, cognitive impairment, and cerebrovascular disease. At 3-month follow-up, the pooled prevalence of fatigue, cognitive impairment, and sleep disorders was still 20% and higher. At six- and 9-month follow-up, there was a tendency for fatigue, cognitive impairment, sleep disorders, anosmia/hyposmia, and headache to further increase in prevalence. At 12-month follow-up, prevalence estimates decreased but remained high for some disorders, such as fatigue and anosmia/hyposmia. Other neurological disorders had a more fluctuating occurrence. DISCUSSION: Neurological manifestations were prevalent during the acute phase of COVID-19 and over the 1-year follow-up period, with the highest overall prevalence estimates for fatigue, cognitive impairment, sleep disorders, anosmia/hyposmia, and headache. There was a downward trend over time, suggesting that neurological manifestations in the early post-COVID-19 phase may be long-lasting but not permanent. However, especially for the 12-month follow-up time point, more robust data are needed to confirm this trend.

The roles of the kynurenine pathway in COVID-19 neuropathogenesis.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the highly contagious respiratory disease Corona Virus Disease 2019 (COVID-19) that may lead to various neurological and psychological disorders that can be acute, lasting days to weeks or months and possibly longer. The latter is known as long-COVID or more recently post-acute sequelae of COVID (PASC). During acute COVID-19 infection, a strong inflammatory response, known as the cytokine storm, occurs in some patients. The levels of interferon-γ (IFN-γ), interferon-ß (IFN-ß), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) are particularly increased. These cytokines are known to activate the enzyme indoleamine 2,3-dioxygenase 1 (IDO-1), catalysing the first step of tryptophan (Trp) catabolism through the kynurenine pathway (KP) leading to the production of several neurotoxic and immunosuppressive metabolites. There is already data showing elevation in KP metabolites both acutely and in PASC, especially regarding cognitive impairment. Thus, it is likely that KP involvement is significant in SARS-CoV-2 pathogenesis especially neurologically.

Neurological and Psychiatric Clinical Manifestations of Sjögren Syndrome.

PURPOSE OF REVIEW: Sjögren Syndrome is a systemic autoimmune disorder that presents mainly with sicca symptoms, but frequently affects other body systems which can lead to a wide variety of manifestations. Understanding the neurological and psychiatric manifestations of Sjögren Syndrome can help with an earlier diagnosis of this disease and leads to better clinical outcomes. RECENT FINDINGS: We provide an updated overview of the central neurological manifestations, peripheral neurological manifestations and psychiatric manifestations and their diagnosis when associated with primary Sjögren Syndrome. The epidemiology and clinical features of the neurological and psychiatric manifestations are derived from different cohort studies and review articles that were selected from PubMed searches conducted between January 2024 and March 2024. The absence of diagnostic criteria and the scarcity of large, robust studies makes the recognition of the neurological and psychiatric manifestations of Sjögren Syndrome more difficult. Maintaining a high index of suspicion in clinical practice and a close collaboration between the Neurologist and the Rheumatologist will facilitate the diagnosis and management of these patients.

Neurological manifestations and risk factors associated with poor prognosis in hospitalized children with Omicron variant infection.

There are increasing reports of neurological manifestation in children with coronavirus disease 2019 (COVID-19). However, the frequency and clinical outcomes of in hospitalized children infected with the Omicron variant are unknown. The aim of this study was to describe the clinical characteristics, neurological manifestations, and risk factor associated with poor prognosis of hospitalized children suffering from COVID-19 due to the Omicron variant. Participants included children older than 28 days and younger than 18 years. Patients were recruited from December 10, 2022 through January 5, 2023. They were followed up for 30 days. A total of 509 pediatric patients hospitalized with the Omicron variant infection were recruited into the study. Among them, 167 (32.81%) patients had neurological manifestations. The most common manifestations were febrile convulsions (n = 90, 53.89%), viral encephalitis (n = 34, 20.36%), epilepsy (n = 23, 13.77%), hypoxic-ischemic encephalopathy (n = 9, 5.39%), and acute necrotizing encephalopathy (n = 6, 3.59%). At discharge, 92.81% of patients had a good prognosis according to the Glasgow Outcome Scale (scores ≥ 4). However, 7.19% had a poor prognosis. Eight patients died during the follow-up period with a cumulative 30-day mortality rate of 4.8% (95% confidence interval (CI) 1.5-8.1). Multivariate analysis revealed that albumin (odds ratio 0.711, 95% CI 0.556-0.910) and creatine kinase MB (CK-MB) levels (odds ratio 1.033, 95% CI 1.004-1.063) were independent risk factors of poor prognosis due to neurological manifestations. The area under the curve for the prediction of poor prognosis with albumin and CK-MB was 0.915 (95%CI 0.799-1.000), indicating that these factors can accurately predict a poor prognosis.          Conclusion: In this study, 32.8% of hospitalized children suffering from COVID-19 due to the Omicron variant infection experienced neurological manifestations. Baseline albumin and CK-MB levels could accurately predict poor prognosis in this patient population. What is Known: • Neurological injury has been reported in SARS-CoV-2 infection; compared with other strains, the Omicron strain is more likely to cause neurological manifestations in adults. • Neurologic injury in adults such as cerebral hemorrhage and epilepsy has been reported in patients with Omicron variant infection. What is New: • One-third hospitalized children with Omicron infection experience neurological manifestations, including central nervous system manifestations and peripheral nervous system manifestations. • Albumin and CK-MB combined can accurately predict poor prognosis (AUC 0.915), and the 30-day mortality rate of children with Omicron variant infection and neurological manifestations was 4.8%.

[Life style drug laughing gas (nitrous oxide, N2O) and the dependency criteria according to ICD-10]. / Trenddroge Lachgas (Distickstoffmonoxid, N2O) und die Abhängigkeitskriterien nach ICD-10.

OBJECTIVE: The increasing popularity of nitrous oxide (N2O) as a recreational drug raises questions about its potential for dependency. This narrative review examines the dependency risk of N2O using the ICD-10 criteria for substance use disorders and evaluates the current literature. MATERIAL AND METHODS: A comprehensive literature search until April 2024 was conducted to identify publications addressing N2O consumption in the context of dependency criteria. The results were analyzed based on the ICD-10 criteria. RESULTS: Studies showed mixed results regarding craving and loss of control among N2O users. There is evidence of neglect of other interests and potential tolerance development, while data on withdrawal symptoms are limited. Persistent consumption despite harmful consequences has been described but objective diagnostic methods to determine consumption intensity are lacking. DISCUSSION: The data on the dependency potential of N2O are inconsistent. The discussion on its classification as an addictive substance remains controversial; however, the clinical indications suggest a possible risk of dependency, especially with excessive consumption. CONCLUSION: Nitrous oxide is currently primarily regarded as a substance of abuse with the potential to foster psychological dependence, manifesting particularly through loss of control and neglect; however, the criteria for physical dependence, such as the occurrence of withdrawal syndromes and the development of tolerance, have not yet been convincingly documented. Further research is needed to better understand the dependency potential of N2O and develop appropriate preventive and therapeutic measures.

Human-derived air-liquid interface cultures decipher Alzheimer's disease-SARS-CoV-2 crosstalk in the olfactory mucosa.

BACKGROUND: The neurological effects of the coronavirus disease of 2019 (COVID-19) raise concerns about potential long-term consequences, such as an increased risk of Alzheimer's disease (AD). Neuroinflammation and other AD-associated pathologies are also suggested to increase the risk of serious SARS-CoV-2 infection. Anosmia is a common neurological symptom reported in COVID-19 and in early AD. The olfactory mucosa (OM) is important for the perception of smell and a proposed site of viral entry to the brain. However, little is known about SARS-CoV-2 infection at the OM of individuals with AD. METHODS: To address this gap, we established a 3D in vitro model of the OM from primary cells derived from cognitively healthy and AD individuals. We cultured the cells at the air-liquid interface (ALI) to study SARS-CoV-2 infection under controlled experimental conditions. Primary OM cells in ALI expressed angiotensin-converting enzyme 2 (ACE-2), neuropilin-1 (NRP-1), and several other known SARS-CoV-2 receptor and were highly vulnerable to infection. Infection was determined by secreted viral RNA content and confirmed with SARS-CoV-2 nucleocapsid protein (NP) in the infected cells by immunocytochemistry. Differential responses of healthy and AD individuals-derived OM cells to SARS-CoV-2 were determined by RNA sequencing. RESULTS: Results indicate that cells derived from cognitively healthy donors and individuals with AD do not differ in susceptibility to infection with the wild-type SARS-CoV-2 virus. However, transcriptomic signatures in cells from individuals with AD are highly distinct. Specifically, the cells from AD patients that were infected with the virus showed increased levels of oxidative stress, desensitized inflammation and immune responses, and alterations to genes associated with olfaction. These results imply that individuals with AD may be at a greater risk of experiencing severe outcomes from the infection, potentially driven by pre-existing neuroinflammation. CONCLUSIONS: The study sheds light on the interplay between AD pathology and SARS-CoV-2 infection. Altered transcriptomic signatures in AD cells may contribute to unique symptoms and a more severe disease course, with a notable involvement of neuroinflammation. Furthermore, the research emphasizes the need for targeted interventions to enhance outcomes for AD patients with viral infection. The study is crucial to better comprehend the relationship between AD, COVID-19, and anosmia. It highlights the importance of ongoing research to develop more effective treatments for those at high risk of severe SARS-CoV-2 infection.

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.

Primary Sjögren syndrome-related peripheral neuropathy: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Primary Sjögren syndrome (pSS) is a chronic, systemic, autoimmune disorder characterized by lymphocytic infiltrates of the exocrine organs, leading to sicca symptoms and parotid enlargement. pSS has been linked to various neurological manifestations, including peripheral neuropathy (PN). We aimed to provide a comprehensive analysis of the currently available evidence regarding pSS-related PN. METHODS: A literature search in the PubMed database was performed, and 49 papers were eligible to be included in this systematic review and meta-analysis. RESULTS: The pooled prevalence of PN in pSS is estimated to be 15.0% (95% confidence interval = 10.7%-20.7%). The mean age of pSS patients at PN diagnosis is 59 years. Among the patients with pSS and PN, 83% are females. Neuropathic symptoms usually precede or lead to the pSS diagnosis at a 2:1 ratio in patients with pSS-related PN. The commonest type of pSS-related PN is distal axonal polyneuropathy (80% of patients with pSS-related PN), followed by sensory ganglionopathy. Peripheral and cranial mononeuropathies-particularly trigeminal-are also frequent. Risk factors for developing PN include increasing age and presence of vasculitis. Immune-mediated pathogenetic mechanisms are discussed. Glucocorticoids are the most commonly used treatment option for managing pSS-related PN, when associated with vasculitis, followed by the use of intravenous immunoglobulin. CONCLUSIONS: PN is very common in pSS patients. Evidence on long-term prognosis of PN in pSS is limited, and further research is needed. Research into the use of immunosuppressive medication in nonvasculitic neuropathies in the context of pSS merits further consideration.

Neurological sequelae after encephalitis associated with herpes simplex virus in children: systematic review and meta-analysis.

BACKGROUND: Encephalitis is an inflammation of the cerebral parenchyma manifested by acute symptoms such as fever, headaches, and other neurological disorders. Its etiology is mostly viral, with herpes simplex virus being a frequent etiological agent in children. The development of neurological sequelae is a serious outcome associated with this infection. OBJECTIVE: To assess the general prevalence and types of neurological sequelae in children after a case of acute viral encephalitis caused by HSV. METHODS: This systematic review and meta-analysis was developed following the PRISMA guidelines. The literature search was carried out in the MEDLINE, Embase, SciELO, LILACS, Cochrane, CINAHL, PsycINFO, and Web of Science databases. Studies were included of children with confirmed HSV infection and that presented a description of neurological sequelae associated with that infection. For the meta-analysis of general prevalence and of the types of neurological sequelae a random effects model was used. RESULTS: Of the 2827 articles chosen in the initial search, nine studies were included in the systematic review and meta-analysis. The general prevalence of neurological sequelae was 50.7% (95% CI 39.2-62.2). The most frequent sequelae were related to mental disability, with a 42.1% prevalence (95% CI 30-55.2); on the other hand, the least frequent sequelae were those related with visual impairment, with a 5.9% prevalence (95% CI 2.2-14.6). The included studies presented regular quality and substantial heterogeneity. CONCLUSION: Even with antiviral therapy, half of patients will develop some type of disability.

Neurological manifestations of COVID-19: a systematic review and detailed comprehension.

The current pandemic caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is accompanied with a rapid increase of reports and papers detailing its neurological effects and symptoms. The virus infection causes respiratory illness named by the world health organization as corona virus 19 (COVID-19).This systematic review aims to study and summarize the different neurological manifestations of this virus. All articles published and indexed via Pubmed, Medline and Google Scholar databases between January 1st 2020 and February 28th 2021 that reported neurological symptoms of SARS-CoV-2 are reviewed following the Preferred Reporting Items for Systemic review and Meta-Analysis (PRISMA) guidelines.We included data from 113 articles: eight prospective studies, 25 retrospective studies and the rest were case reports/series. COVID-19 can present with central nervous system manifestations, such as headache, encephalitis and encephalopathy, peripheral nervous system manifestations, such as anosmia, ageusia and Guillian Barre syndrome, and skeletal muscle manifestations, such as myalgia and myasthenia gravis. Our systematic review showed that COVID-19 can be manifested by a wide spectrum of neurological symptoms reported either in the early stage or within the course of the disease. However, a detailed comprehension of these manifestations is required and more studies are needed in order to improve our scientific knowledge and to develop preventive and therapeutic measures to control this pandemic.

[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.

Course of fatigue among patients previously hospitalised due to COVID-19.

INTRODUCTION: Discrepancies exist regarding the clinical course and prognostic factors for post-COVID fatigue. Therefore, our aim was to assess the timely course of fatigue and its possible predictors in patients previously hospitalised due to SARS-CoV-2 infection. MATERIAL AND METHODS: Patients and employees of the University Hospital in Krakow were assessed with the use of a validated neuropsychological questionnaire. Included were participants aged 18 or more, previously hospitalised due to COVID-19, who completed questionnaires only once > 3 months after the onset of infection. Individuals were retrospectively asked about the presence of eight symptoms of chronic fatigue syndrome at four timepoints: before COVID-19, within 0-4 weeks, 4-12 weeks, and > 12 weeks post-infection. RESULTS: We enrolled 204 patients [40.2% women, median age 58 (46-66) years] evaluated after a median of 187 (156-220) days from the first positive nasal swab test for SARS-CoV-2. The most common comorbidities were hypertension (44.61%), obesity (36.27%), smoking (28.43%), and hypercholesterolemia (21.08%); none of the patients required mechanical ventilation during hospitalisation. Before COVID-19, 43.62% of patients reported at least one symptom of chronic fatigue. Within 4, 4-12, and > 12 weeks after COVID-19, the prevalence of chronic fatigue was 76.96%, 75.49%, and 66.17%, respectively (all p < 0.001). The frequency of chronic fatigue symptoms decreased within > 12 weeks following the onset of infection but did not return to baseline values, except for self-reported lymph node enlargement. In a multivariable linear regression model, the number of fatigue symptoms was predicted by female sex [ß 0.25 (0.12; 0.39), p < 0.001 and 0.26 (0.13; 0.39), p < 0.001 for weeks 0-12 and > 12, respectively], and age [for < 4 weeks, ß -0.12 (-0.28; -0.01), p = 0.029]. CONCLUSIONS: Most patients previously hospitalised due to COVID-19 suffer from fatigue > 12 weeks after infection onset. The presence of fatigue is predicted by female sex and - only for the acute phase - age.

Neurological and neuropsychiatric manifestations in hospitalised patients with COVID-19.

Background: Although literature globally indicates varied neurological and/or neuropsychiatric manifestations (NNM) and complications associated with coronavirus disease 2019 (COVID-19), information about NNM in infected hospitalised patients on the African continent remains limited. Aim: To describe the presentation of NNM and compare patients with and without NNM considering demographic and clinical profiles, treatment, and outcomes. Setting: Tygerberg Hospital, Cape Town, South Africa. Methods: Retrospective medical record review of the first 100 consecutively admitted COVID-19 patients (64 females, mean age 47.6 years) between March and June 2020. Results: Of the 98 patients included in the analysis, 56.1% had at least one NNM. The most common NNM were myalgia (32.7%), headache (21.4%), loss of smell and/or taste (15.3%), and delirium (10.2%). Patients with and without NNM did not differ with respect to demographic characteristics. Patients with NNM had significantly more constitutional symptoms (p = 0.017) and were more likely to have neurological and/or neuropsychiatric comorbid conditions (10.9% vs. 0.0%, p = 0.033) than those without NNM. Patients without documented NNM were more likely to have abnormalities on chest X-ray (p = 0.009) than those with NNM. Coronavirus disease 2019 related treatment and mortality did not differ between the groups. Conclusion: Neurological and/or neuropsychiatric manifestations were common in hospitalised patients with COVID-19. The results suggest that while COVID-19 patients with NNM may have less of a respiratory phenotype they nonetheless have equivalent mortality rates. Contribution: This study highlights the common NNM in patients with COVID-19 admitted to Tygerberg Hospital early in the pandemic and adds to the growing evidence of COVID-19 NNM.

Neurological manifestations in mevalonate kinase deficiency: A systematic review.

INTRODUCTION: Mevalonate kinase deficiency (MKD) is a monogenic auto-inflammatory disease. Its manifestations range from partial MKD to mevalonic aciduria (MVA). All patients display a periodic fever, and MVA patients additionally exhibit severe neurological involvement. The objective of this work was to describe neurological manifestations of MKD. METHODS: A systematic literature review was performed from January 1990 to January 2022. Forty-five patients from 18 case reports and five cohort studies were included in the analysis. RESULTS: In cohort studies, the most-reported manifestations were headaches (41%) and fatigue (31%). Serious involvements including ataxia and developmental delay were described less than 1% of patients but 22-31% of case reports. They consistently appeared in the first years of life. Retinal dystrophy was frequently reported (31%) in case reports. Other manifestations, including uveitis, aseptic meningitis, and stroke remained rare. DISCUSSION: Severe neurological manifestations are rare in MKD but are responsible for major functional disabilities. They are present at onset and never appear at follow-up of patients with mild MKD. Conversely, headaches and fatigue are frequent symptoms that should be investigated. Visual examinations should be performed on the appearance of visual symptoms. The efficacy of anti-IL-1ß therapy on neurological manifestations should be further investigated.