MECHANISMS OF CENTRAL NERVOUS SYSTEM DAMAGE IN COVID-19

The issues of diagnosis and treatment of nervous system damage in the new coronavirus infection (COVID-19) remain relevant, regardless of information and experience in treating such patients, accumulated nowadays. The review contains updated data on the ways of SARS-CoV-2 invasion, examines mechanisms of central nervous system damage: direct virus-induced damage, immune dysfunction, excessive thrombo-inflammation, coagulation disorder, cytokine and metabolic imbalance, hypoxia, etc.;it presents clinical examples with one variant of damage — the development of Guillain-Barre syndrome that, to some extent, allows to confirm the virus neurotropism. Doctors' knowledge about this infection is constantly expanding, new information appears on its various neuropsychiatric effects during an acute period and post-COVID syndrome, on symptoms, treatment and prevention strategy. These data enables to understand better the reasons for developing the main clinical manifestations, from a headache or myalgia to more severe symptoms, such as a stroke, psychosis and anosmia, severity and reversibility of their course. Although several hypothesis of CNS damage pathogenesis in COVID-19 are being discussed, the unified pathophysiological mechanism of many dysfunctions remains unclear, and, probably, additional factors, such as social isolation during a pandemic, presence and treatment in the intensive care unit, premorbid somatic status of a patient, contribute to the development of some registered nervous system disorders. © 2023, HIV Infection and Immunosuppressive Disorders.All Rights Reserved.

Association Between COVID-19 Pandemic and Serious Mental Illness: Systematic Review within Salutogenesis Model for Public Health Management

Background: The outbreak of the COVID-19 pandemic, the constant transformation of the SARS-COV-2 virus form, exposure to substantial psychosocial stress, environmental change, and isolation have led to the inference that the overall population's mental health could be affected, resulting in an increase in cases of psychosis. Objective(s): We initiated a systematic review to determine the impact of the SARS-COV-2 virus and its long-term effects-in both symptomatic and asymptomatic cases-on people with or without psychosis. We envisioned that this would give us an insight into effective clinical intervention methods for patients with psychosis during and after the pandemic. Method(s): We selected fifteen papers that met our inclusion criteria, i.e., those that considered participants with or without psychiatric illness and exposed to SARS-COV-2 infection, for this review and were retrieved via Google, Google Scholar, MEDLINE, PubMed, and PsychINFO Database. Key Gap: There is a dearth of research in understanding how COVID-19 affects people with or without a prior personal history of psychosis. Result(s): The systematic review summary provides insight into the state of knowledge. Insights from the systematic review have also been reviewed from the salutogenesis model's perspec-tive. There is moderate evidence of new-onset psychosis during the COVID-19 pandemic in which some antipsychotics treated the psychotic symptoms of patients while treating for COVID-19. Suggestions and recommendations are made for preventive and promotive public health strategies. Conclusion(s): The Salutogenesis model and Positive Psychology Interventions (PPI) provide another preventive and promotive public health management approach.Copyright © 2023 Bentham Science Publishers.

Research Guillain-Barre Syndrome During the COVID-19 Pandemic and Pre-pandemic Periods

Background: Guillain-Barre Syndrome (GBS) is an autoimmune disease that may occur after infections.As Coronavirus Disease 2019 (COVID-19) may bring about GBS, it is important to assess the effect of the COVID-19 pandemic on this diseaseObjectives: This study aimed to compare the distribution and characteristics of GBS during and before theCOVID-19 pandemic in an academic referral hospital in the north of Iran.Materials & Methods: This retrospective study assessed GBS distribution and characteristics during theCOVID-19 pandemic period (from March 2020 to the end of February 2021) and before the pandemic(from March 2019 to the end of February 2020) on 5340 patients referred to the Neurology Ward ofPoursina Hospital of Guilan Province, in Iran. Result(s): There was no significant difference between GBS distribution during (0.03%) and before (0.04%)the COVID-19 pandemic (P=0.413). There were also no differences between the two periods regardingthe gender (P=0.659) and age (P=0.417) of the patients. The most common subtype of GBS during theCOVID-19 pandemic was Acute Motor and Sensory Axonal Neuropathy (AMSAN) (71.4%). In bothperiods, the most common type of treatment was intravenous administration of immune globulin. Therewas no significant difference between the two periods (P=0.838) regarding the patients' treatment response. Conclusion(s): The distribution of GBS, its subtypes, type of treatment, and response to treatment were notdifferent between the two study periodsCopyright © 2018 The Authors. This is an open access article under the CC-By-NC license

Case report: COVID-19-associated refractory thrombotic thrombocytopenic purpura complicated with Guillain-Barré syndrome.

Thrombotic thrombocytopenic purpura (TTP), a rare and lethal thrombotic microangiopathy, is an autoimmune disease that can be triggered by viral infections such as COVID-19. This condition is characterized by hemolytic microangiopathy, thrombocytopenia, and neurologic alterations, possibly accompanied by fever and renal damage. Moreover, more than 220 patients with Guillain-Barré syndrome (GBS) have been reported in association with the COVID-19 infection. In this report, we present a case of a patient who developed refractory TTP complicated by GBS following a SARS-CoV-2 infection. We aimed to highlight the importance of accurately diagnosing neurological complications associated with a COVID-19 infection and to demonstrate our strategies for treating a patient with COVID-19 infection-related refractory TTP complicated by GBS.

Guillain-Barré syndrome following COVID-19 vaccination: An updated systematic review of cases.

Key Clinical Message: Guillain-Barré syndrome (GBS) is a rare but possible complication that may occur after COVID-19 vaccination. In this systematic review, we found that GBS presented in patients with an average age of 58. The average time for symptoms to appear was 14.4 days. Health care providers should be aware of this potential complication. Abstract: Most instances of Guillain-Barré syndrome (GBS) are caused by immunological stimulation and are discovered after vaccinations for tetanus toxoid, oral polio, and swine influenza. In this systematic study, we investigated at GBS cases that were reported after receiving the COVID-19 vaccination. Based on PRISMA guidelines, we searched five databases (PubMed, Google Scholar, Ovid, Web of Science, and Scopus databases) for studies on COVID-19 vaccination and GBS on August 7, 2021. To conduct our analysis, we divided the GBS variants into two groups, acute inflammatory demyelinating polyneuropathy and non-acute inflammatory demyelinating polyneuropathy (AIDP and non-AIDP), and compared the two groups with mEGOS and other clinical presentation In this systematic review, 29 cases were included in 14 studies. Ten cases belonged to the AIDP variant, 17 were non-AIDP (one case had the MFS variant, one AMAN variant, and 15 cases had the BFP variant), and the two remaining cases were not mentioned. Following COVID-19 vaccination, GBS cases were, on average, 58 years of age. The average time it took for GBS symptoms to appear was 14.4 days. About 56 percent of the cases (56%) were classified as Brighton Level 1 or 2, which defines the highest level of diagnostic certainty for patients with GBS. This systematic review reports 29 cases of GBS following COVID-19 vaccination, particularly those following the AstraZeneca/Oxford vaccine. Further research is needed to assess all COVID-19 vaccines' side effects, including GBS.

Peripheral nervous system involvement in SARS-CoV-2 infection: a review of the current pediatric literature.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the pathogen responsible for the pandemic health emergency declared by the World Health Organization in March 2020. During the first part of the pandemic, adults showed mild to severe respiratory symptoms. Children seemed initially exempt, both from acute and subsequent complications. Hyposmia or anosmia were promptly identified as the main symptoms of acute infection, so neurotropism of SARS-CoV-2 was immediately suspected. (1, 2). As the emergency progressed, post infectious neurological complications were described also in pediatric population (3). Cases of cranial neuropathy in connection with acute SARS-CoV-2 infection have been reported in pediatric patients, as an isolate post infectious complication or in the context of the multisystem inflammatory syndrome in children (MIS-C) (4-6). Neuroinflammation is thought to be caused by several mechanisms, among which immune/autoimmune reactions (7), but so far, no specific autoantibody has been identified. SARS-CoV-2 can enter the central nervous system (CNS) directly and/or infect it retrogradely, through the peripheral nervous system (PNS), after replicating peripherally; several factors regulate invasion and subsequent neuroinflammation. Indeed, direct/secondary entry and replication can activate CNS-resident immune cells that, together with peripheral leukocytes, induce an immune response and promote neuroinflammation. In addition, as we will discuss in the following review, many cases of peripheral neuropathy (cranial and non-cranial) have been reported during or after SARS-CoV-2 infection. However, some authors have pointed out that the increase of cranial roots and ganglia in neurological imaging is not always observed in children with cranial neuropathy. (8). Even if a variety of case reports were published, opinions about an increased incidence of such neurologic diseases, linked to SARS-CoV-2 infection, are still controversial (9-11). Facial nerve palsy, ocular movements abnormalities and vestibular alterations are among the most reported issues in pediatric population (3-5). Moreover, an increased screen exposure imposed by social distancing led to acute oculomotion's disturbance in children, not primarily caused by neuritis (12, 13). The aim of this review is to suggest food for thought on the role of SARS-CoV-2 in neurological conditions, affecting the peripheral nervous system to optimize the management and care of pediatric patients.

Rheumatoid Vasculitis Complicated With Acute Inflammatory Demyelinating Polyneuropathy in an Older Female: A Case Report.

Rheumatoid vasculitis (RV) causes various complications in the heart, lungs, kidneys, and nerves that require intensive treatment. Rapid RV-related peripheral nerve involvement progression is critical and requires prompt treatment. We report the case of a 73-year-old female with RV, with a chief complaint of difficulty walking without any infectious symptoms for several months. We diagnosed Guillain-Barré syndrome (GBS) accompanied by RV and treated the patient with intravenous immunoglobulin and cyclophosphamide. Previous impairments of activities of daily living (ADLs) were resolved. Diagnosing the neurological manifestations of RV and GBS in older patients with an active RV is challenging because of the various patterns of the progression. For effective management, considering both diseases and implementing immunosuppressive and modulatory treatments is critical to stop the progression of neurological symptoms and prevent the deterioration of ADLs.

Neuromuscular disease: 2022 update.

This review highlights ten important advances in the neuromuscular disease field that were reported in 2021. As with prior updates in this article series, the overarching topics include (i) advances in understanding of fundamental neuromuscular biology; (ii) new / emerging diseases; (iii) advances in understanding of disease etiology and pathogenesis; (iii) diagnostic advances; and (iv) therapeutic advances. Within this general framework, the individual disease entities that are discussed in more detail include neuromuscular complications of COVID-19 (another look at the topic first covered in the 2021 review), autosomal recessive myopathy caused by MLIP mutations, autosomal recessive neuromuscular disease caused by VWA1 mutations, Leber's hereditary optic neuropathy, myopathies with autophagic defects, tRNA synthetase-associated Charcot-Marie-Tooth disease, systemic sclerosis-associated myopathy, humoral immune endoneurial microvasculopathy, and late-onset Pompe disease. In addition, the review highlights a few other advances (including new insights into mechanisms of muscle and nerve regeneration and the use of gene expression profiling to better characterize different subtypes of immune-mediated myopathies) that will be of significant interest for clinicians and researchers who specialize in neuromuscular disease.

Neuromuscular disease: 2021 update.

This review highlights ten important advances in the neuromuscular disease field that were first reported in 2020. The overarching topics include (i) advances in understanding of fundamental neuromuscular biology; (ii) new / emerging diseases; (iii) advances in understanding of disease etiology and pathogenesis; (iv) diagnostic advances; and (v) therapeutic advances. Within this broad framework, the individual disease entities that are discussed in more detail include neuromuscular complications of COVID-19, supervillin-deficient myopathy, 19p13.3-linked distal myopathy, vasculitic neuropathy due to eosinophilic granulomatosis with polyangiitis, spinal muscular atrophy, idiopathic inflammatory myopathies, and transthyretin neuropathy/myopathy. In addition, the review highlights several other advances (such as the revised view of the myofibrillar architecture, new insights into molecular and cellular mechanisms of muscle regeneration, and development of new electron microscopy tools) that will likely have a significant impact on the overall neuromuscular disease field going forward.

Atypical Guillain-Barre Syndrome With a Sensory Level and Hyper-Acute Presentation: A Case Report.

A 46-year-old man with a prior history of cervical spondylosis and myelopathy needing cervical spinal surgery three years back presented to the emergency department with acute onset areflexic flaccid weakness of both lower extremities, with a sensory level at T10. Magnetic resonance imaging studies (MRI) of the cervical, thoracic, and lumbar spine ruled out significant cord compression, spinal cord ischemia, spinal shock, or findings to suggest transverse myelitis. CSF analysis showed normal albumin and protein; however, with the features of paraplegia with flaccidity, areflexia, absence of bowel and bladder symptoms, and MRI ruling out other possibilities, a diagnosis of Guillain-Barre syndrome (GBS) was made. The patient was treated with intravenous immunoglobulin (IVIG) and showed a clinical response, with improvement in strength in both lower extremities. This case is rare and unique, as it exhibits atypical features for a GBS case, including a sensory level and hyper-acute presentation, with the onset of weakness to a nadir within an hour. This case highlights the importance of awareness of such atypical GBS presentations so that the diagnosis is not missed and is appropriately managed for favorable patient outcomes.

Corrigendum: Incidence of Guillain-Barré syndrome in South Korea during the early COVID-19 pandemic.

[This corrects the article DOI: 10.3389/fneur.2023.1125455.].

How is Guillain-Barre syndrome associated with COVID-19 infection differentiated from hypokalemic periodic paralysis? a case report.

Patients with coronavirus disease 2019 (COVID-19)-associated Guillain-Barre syndrome (GBS) exhibit a range of clinical symptoms, such as cranial nerve paralysis and axonal or motor-sensory electrophysiological signals. Case presentation: A 61-year-old retired black African female was brought into the emergency room on 13 May 2022, with a 4-day history of shortness of breath and high-grade fever and a 1-day history of global body weakness (bilateral paralysis of the upper and lower extremities). Motor examination indicated reduced muscular strength in all limbs, with a Medical Research Council score of 2/5 in the right arm of the upper extremities, 1/5 in the right leg of the lower extremities, 1/5 in the left leg of the lower extremities, and 2/5 in the left arm of the upper extremities. Her electrocardiogram revealed ST depression in the anterior-lateral leads and sinus tachycardia. For the COVID-related infection, azithromycin 500 mg per day for 5 days was begun. After cerebrospinal fluid findings supported the diagnosis of GBS, she underwent intravenous immunoglobulin 400 mg/kg every day for 5 days. Clinical discussion: In the majority of COVID-19-related GBS cases, areflexic quadriparesis developed suddenly. A COVID-19 infection related to a GBS case was the only one that had preceding signs, including ageusia and hyposmia. By testing serum potassium levels, this study determined that there is no connection between GBS and hypokalemia, which can lead to diagnostic and therapeutic conundrums by evaluating serum potassium levels, which showed a normal value. Conclusion: One of the neurological symptoms of the COVID-19 infection is GBS. Several weeks after a COVID-19 acute infection, GBS is frequently observed.

Autoimmune Peripheral Neuropathies

Autoimmune peripheral neuropathies (APNs) occur when immunological tolerance to peripheral nerve components (myelin, axon, or ganglionic neurons) is lost. The most common APNs are acute inflammatory polyneuropathies, such as Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN), immunoglobulin M (IgM)–anti–myelin-associated glycoprotein (MAG) antibody–mediated paraproteinemic neuropathy, and those caused by vasculitis or viral infections. Both cellular and humoral factors, either independently or in concert with each other, appear to play a role, but the specific immune mechanisms have not been fully elucidated. Infectious agents, such as Campylobacter jejuni and Zika virus via molecular mimicry, and now COVID-19, are implicated in some GBS subtypes, but the factors that break tolerance in the other APNs remain unknown. In some acute or chronic APN, antibodies against peripheral nerve glycolipids or glycoproteins are pathogenic and well characterized. Pathogenic IgG4 antibodies against antigens at the nodes of Ranvier that cause disadhesion of nodal and paranodal proteins and conduction block define distinct CIDP subtypes, which respond only to rituximab. Some newly emerging, not pathogenic, autoantibodies more commonly seen in small fiber sensory neuropathies and neuropathic pains are briefly discussed. The current immunotherapies in all APNs are described based on controlled trials or clinical experience. © 2023 Elsevier Ltd. All rights reserved.

Ndegree39 - Fulminant life-threatening myopathy of the genetic origin

Objectives: Acute myopathy are seen in critically ill patients, in severe SARS-CoV2 pneumonia requiring mechanical ventilation, and other infection illness, toxin and drug-induced complications, or systemic inflammation. Periodic paralysis or carnitine disorders are known genetic causes of acute muscular weakness, besides genetically determined muscle diseases rarely have an acute clinical course. Content: Case presentation: 61-years old, healthy woman, after a one-time vaccination against Covid-19 about 2 weeks earlier, was admitted to the Neurological Department due to symptoms lasting for 2 days. On the first day of the disease she complained of vertigo and double vision, on the following day dysarthia and dysphagia appeared, she stopped walking. On the second day of hospitalization, the patient required mechanical ventilation. The initial diagnosis of Guillaine-Barre syndrome was not confirmed in the electrophysiological and laboratory (CSF) studies. Myopathic pattern with polyphasic potentials of short duration and low amplitude was observed in EMG, without spontaneous activity. In the electron microscope numerous fat drops between bundles of myofibrils in most muscle fibers were seen. She received intravenous immunoglobulins, and steroid therapy, together with high doses of vitamin B2 with very good motor improvement. Multiple acyl-CoA dehydrogenase deficiency (MADD) was suspected, and the Whole Exome Sequencing (WES) was performed. Conclusion(s): The authors note the possibility of acute, life-threatening myopathy, which may be caused by a genetic defect. MADD is a very rare genetic entity which can manifest for the first time very suddenly, especially in the presence of triggers, including but not limited to after vaccinations. Keywords: Acute myopathy;Multiple acyl-CoA dehydrogenase deficiency;Vitamin B2.Copyright © 2023

Guillain-Barré Syndrome Following the BNT162b2 mRNA COVID-19 Vaccine

PURPOSE: The onset of the COVID-19 (SARS-CoV-2) pandemic in December 2019 created the need for multiple scientific research activities and clinical trials in an attempt to find solutions to mitigate the impact of the virus. One of the important tools to combat the virus is the development of vaccination programs. All types of vaccines have been associated with a mild to severe risk of neurological adverse events. One of these severe adverse events is Guillain-Barré syndrome. CASE REPORT: Here, we describe a case of Guillain-Barré syndrome after the first dose of the BNT162b2 mRNA COVID-19 vaccine and review the literature to increase the current knowledge regarding this complication. CONCLUSION: Guillain-Barré syndrome after COVID-19 vaccination is responsive to treatment. The benefits of administering the vaccine outweigh the risks. Due to the negative impact of COVID-19, it is essential to recognize the development of neurological complications that are potentially associated with vaccination, including Guillain-Barré syndrome.

Guillain-Barré syndrome associated with SARS-CoV-2 vaccination: how is it different? a systematic review and individual participant data meta-analysis.

Purpose: An association between Guillain-Barré syndrome (GBS) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination has been reported. We aimed to summarize the clinical features of GBS associated with SARS-CoV-2 vaccination and determine the contrasting features from coronavirus disease-19 (COVID-19) associated GBS and GBS following other causes. Materials and Methods: We performed PubMed search for articles published between 1 December 2020 and 27 January 2022 using search terms related to "SARS-CoV-2 vaccination" and "GBS". Reference searching of the eligible studies was performed. Sociodemographic and vaccination data, clinical and laboratory features, and outcomes were extracted. We compared these findings with post-COVID-19 GBS and International GBS Outcome Study (IGOS) (GBS from other causes) cohorts. Results: We included 100 patients in the analysis. Mean age was 56.88 years, and 53% were males. Six-eight received non-replicating virus vector and 30 took messenger RNA (mRNA) vaccines. The median interval between the vaccination and the GBS onset was 11 days. Limb weakness, facial palsy, sensory symptoms, dysautonomia, and respiratory insufficiency were seen in 78.65%, 53.3%, 77.4%, 23.5%, and 25%, respectively. The commonest clinical and electrodiagnostic subtype were sensory-motor variant (68%) and acute inflammatory demyelinating polyneuropathy (61.4%), respectively. And 43.9% had poor outcome (GBS outcome score ≥3). Pain was common with virus vector than mRNA vaccine, and the latter had severe disease at presentation (Hughes grade ≥3). Sensory phenomenon and facial weakness were common in vaccination cohort than post-COVID-19 and IGOS. Conclusion: There are distinct differences between GBS associated with SARS-CoV-2 vaccination and GBS due to other causes. Facial weakness and sensory symptoms were commonly seen in the former and outcomes poor.

Guillain-Barré Syndrome Induced by Vaccination Against COVID-19: A Systematic Review and Meta-Analysis.

Guillain-Barré syndrome (GBS) is a rare but serious immune-mediated neurological condition characterized by damage to the peripheral nervous system. Two-thirds of cases of GBS are diagnosed following infection; however, vaccination has also been linked to GBS pathogenesis. The aim of this systematic review and meta-analysis was to establish the prevalence of GBS following vaccination against the SARS-CoV-2 virus, which causes COVID-19, describe the clinical and neurophysiological characteristics, and identify potential determinants. A systematic review of the literature regarding post-vaccination GBS was conducted using the PubMed database. Seventy papers were included. The pooled prevalence of GBS after vaccination against COVID-19 per has been established to be 8.1 (95% CI 30-220) per 1,000,000 vaccinations. Vaccination with vector vaccines - but not mRNA - has been associated with an increased risk of GBS. More than 80% of the patients developed GBS within 21 days following the first dose of the vaccination. The interval between the vaccination and GBS was shorter in patients who were vaccinated with mRNA versus vector vaccines (9.7±6.7 days versus 14.2±6.6 days). Epidemiological findings regarding post-vaccination GBS revealed a higher prevalence in males and people between the ages of 40 and 60 years, with a mean age of 56.8±16.1 years. The most common type was the acute inflammatory demyelinating polyneuropathy type. Most cases responded well to treatment. In conclusion, vaccination against COVID-19 with vector vaccines seems to increase the risk of GBS. GBS occurring following vaccination does differ in characteristics from GBS during the pre-COVID-19 era.

Post-COVID-19 vaccination Guillain-Barre syndrome with sensory ataxia, gaze-evoked nystagmus, mental-status change and positive pathological reflex

Background: Various neurological disorders have been reported after vaccination against coronavirus disease 2019, one of which is Guillain-Barre Syndrome (GBS). Case Presentation: We report a case of a 73-year-old woman who developed GBS and extra-GBS manifestations 19 days after the second dose of BNT162b2 mRNA vaccine. She presented lower limb predominant muscle weakness and loss of tendon reflexes. Nerve conduction study showed acute motor and sensory axonal neuropathy. In addition, she developed notable deep sensory ataxia, and showed positive pathological reflex, gaze-evoked nystagmus and altered consciousness, which suggested brainstem involvement. Conclusion(s): This is the first coronavirus disease 2019 vaccine-related GBS complicated with such central nervous system manifestations.Copyright © 2023 Japanese Society for Neuroimmunology.