Neurological complications in patients with SARS-CoV-2 infection: a systematic review

ABSTRACT Background: As the COVID-19 pandemic unfolds worldwide, different forms of reports have described its neurologic manifestations. Objective: To review the literature on neurological complications of SARS-CoV-2 infection. Methods: Literature search performed following systematic reviews guidelines, using specific keywords based on the COVID-19 neurological complications described up to May 10th, 2020. Results: A total of 43 articles were selected, including data ranging from common, non-specific symptoms, such as hyposmia and myalgia, to more complex and life-threatening conditions, such as cerebrovascular diseases, encephalopathies, and Guillain-Barré syndrome. Conclusion: Recognition of neurological manifestations of SARS-CoV-2 should be emphasized despite the obvious challenges faced by clinicians caring for critical patients who are often sedated and presenting other concurrent systemic complications.

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Acute Neurological Manifestations of Porphyrias and its Types: A Systematic-Review

Cardiovascular & Hematological Agents in Medicinal Chemistry ◽

10.2174/1871525718666200910162000 ◽

2020 ◽

Vol 18 ◽

Author(s):

Enrico Affonso Barletta ◽

Telmo Augusto Barba Belsuzarri ◽

Augusto Ricardo Barba Urena ◽

Eduardo Augusto Iunes

Keyword(s):

Systematic Review ◽

Clinical Presentation ◽

Neurological Manifestations ◽

Consciousness Disturbance ◽

Life Threatening ◽

Low Incidence ◽

Treatment Onset ◽

Acute Porphyrias ◽

Specific Symptoms ◽

Psychiatric Manifestations

: Acute porphyrias cause life-threatening attacks of neurovisceral non-specific symptoms, so this condition mimics many acute medical and psychiatric diseases. The disease is very misdiagnosed, probably due to its low incidence and nonpathognomonic symptoms, this delays the effective treatment onset. Early diagnosis and treatment improve highly the prognosis and can prevent the development of neuropathic manifestations. We assembled a systematic review, following the PRISMA guidelines and using Pubmed as our database. Our aim is to show some peculiarities among patients that present neurological manifestations in acute porphyria attack. We have obtained the patients age, sex, clinical presentation, neurological manifestations and porphyria type out of 16 patients. We also evaluated the time between symptoms onset and neurological manifestations. The average age was 28,4 ± 11,1; 50% of patients were male. AIP was the most prevalent porphyria type. The average time between symptoms onset and neurological manifestations was of 9,53 ± 11,6 days. Abdominal pain; nausea and vomiting and psychiatric manifestations were the most common symptoms preceding neurological attacks. Seizures and consciousness disturbance were the most prevalent findings within an attack. We are also presenting a case to illustrate how difficult this diagnosis can be.

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Neurological manifestations associated with SARS-CoV-2 infection: a narrative review

10.5327/1516-3180.442 ◽

2021 ◽

Author(s):

Poliana Rafaela dos Santos Araújo ◽

Kauan Alves Sousa Madruga ◽

Bruna Alves Rocha ◽

Lucas Oliveira Braga

Keyword(s):

Nervous System ◽

Meta Analysis ◽

Neurological Complications ◽

Neurological Symptoms ◽

Narrative Review ◽

Common Symptom ◽

Neurological Manifestations ◽

Cns Involvement ◽

Pubmed Database ◽

Critical Patients

Background: Coronavirus disease (COVID-19), once identified, soon spread globally, becoming a pandemic. Although patients present mainly with respiratory complaints, several neurological symptoms have been reported. Symptoms range from headache and nonspecific dizziness to seizures and cerebrovascular disease (CVD). It has also been shown that the severity of the infection is directly proportional to the development of neurological symptoms, especially CVD and changes in mental status. Objective: The present study aims to briefly review the neurological manifestations of COVID-19 and discuss the pathogenic mechanisms of Central Nervous System (CNS) involvement. Methods: This is an exploratory narrative review with a descriptive approach, consisting of an active search for scientific articles in the PubMed database. The descriptors “coronavirus infections”, “COVID-19” and “Nervous system” were used, with the Boolean operators “OR” and “AND”. Eighteen articles of systematic review and meta-analysis were included. Results: CNS manifestations included, among others: encephalitis, encephalopathy, consciousness decrease, headache, dizziness, acute myelitis, and stroke. As for the peripheral nervous system, skeletal muscle damage, chemosensory dysfunction, and Guillain-Barré syndrome were observed, with hyposmia being the most common symptom. CNS involvement may be related to a worse prognosis. Conclusion: The clinical involvement of the nervous system in COVID-19 is not uncommon, and can result in several neurological complications, especially in the most critical patients. The pathophysiological mechanisms of these events still need further investigation. In the meantime, physicians should value extra-respiratory symptoms ranging from hyposmia, to potentially fatal manifestations, such as stroke and encephalopathy.

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Epileptic seizures in patients with COVID-19: A systematic review of early evidences

Journal of Biomedical Sciences ◽

10.3126/jbs.v8i1.38459 ◽

2021 ◽

Vol 8 (1) ◽

pp. 33-44

Author(s):

B Roy ◽

I Banerjee

Keyword(s):

Systematic Review ◽

Epileptic Seizure ◽

Case Reports ◽

Neurological Complication ◽

Epileptic Seizures ◽

Neurological Complications ◽

Cross Sectional Study ◽

Cerebrovascular Diseases ◽

Cross Sectional ◽

Demyelinating Lesions

Background: Global emergence of SARS-CoV-2 surfaced neurological complications amongst the patients. COVID-19 resembles with other coronavirus strains follows a trend of neurological complication, damage and encephalopathy, which entails considerable risks, requires attention for the neurologists. This is, to our knowledge, the first systematic review of the literature to investigate solely to elucidate the seizure spectrum by unfolding epileptogenicity of the SARS CoV-2 and potential pathways of neuroinvasion. Methods: A systematic literature search was performed in PubMed and Embase database following standard guidelines, using specific keywords based on epileptic seizure onset described from December 01, 2019, to July 17, 2020 Results: A total of 17 studies were included ranging from case reports, series of cases, multicentre cross-sectional study with the first-time onset of seizure associated with an epileptic origin. We excavated causes of complex COVID-19 related neurological manifestations, e.g., cerebrovascular diseases, encephalitis, demyelinating lesions, cytokine storm and proposed routes of SARS-CoV-2 entry into the nervous system to understand the mechanism of an epileptic seizure. Conclusion: COVID-19 is a potent neuropathogen which causes the new onset of epileptic seizures should get diagnostic recognition to evade possible deterioration of neurological conditions. However, more shreds of evidence from the future will further elucidate the epileptogenic potential of the pandemic.

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A Systematic Review of Severe Neurological Manifestations in Pediatric Patients with Coexisting SARS-CoV-2 Infection

Neurology International ◽

10.3390/neurolint13030041 ◽

2021 ◽

Vol 13 (3) ◽

pp. 410-427

Author(s):

Lauren O’Loughlin ◽

Nilo Alvarez Toledo ◽

Leon Budrie ◽

Randall Waechter ◽

Joanna Rayner

Keyword(s):

Systematic Review ◽

Immune Response ◽

Neurological Disorders ◽

Respiratory Symptoms ◽

Literature Search ◽

Pediatric Patients ◽

Neurological Manifestations ◽

Critical Factors ◽

Age Range ◽

Inflammatory Syndrome

SARS-CoV-2 infection in children produces mild respiratory symptoms or no symptoms at all in most cases. Some pediatric patients develop a severe complication associated with high mortality, the multisystem inflammatory syndrome in children (MIS-C). In both scenarios, there are reports of neurological manifestations. This article aims to review the cases of pediatric patients with severe neurological issues and a coexisting positive SARS-CoV-2 test. A literature search was performed between March 2020 and May 2021. The results included the data from 41 studies, with 159 children with severe neurological manifestations, within an age range from 24 h to 17 years. The neurological disorders included 38 cases with stroke, 32 with encephalitis, 22 with encephalopathy, and 10 with Guillain–Barre syndrome. Sixty-five out of 159 cases with severe neurological manifestations were diagnosed with MIS-C. Direct neuroinvasion and the exaggerated immune response in some patients seem to be the most critical factors triggering these manifestations. Further research in the ongoing pandemic is needed to elucidate the precise mechanism.

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A Comprehensive Systematic Review of CSF analysis that defines Neurological Manifestations of COVID-19

10.21203/rs.3.rs-96718/v1 ◽

2020 ◽

Author(s):

Medha Tandon ◽

Tejas R Mehta ◽

Maha Daimee ◽

Viral Patel ◽

Apoorv Prasad ◽

...

Keyword(s):

Systematic Review ◽

Neurological Complications ◽

Common Finding ◽

Pathophysiological Mechanism ◽

Neurological Manifestations ◽

Protein Levels ◽

Csf Analysis ◽

Cell Counts ◽

Neurological Illness ◽

Elevated Protein

Abstract Background: Here we performed a systematic review of literature of CSF findings associated with neurological complications in coronavirus disease-2019 (COVID-19) to establish a pattern and understand the significance of CSF analysis which can possibly be useful in deciding prognosis and exploring therapeutic options in the future. Methods: We screened all articles resulting from a search of PubMed, Google Scholar and Scopus, using the keywords “SARS-CoV-2 in cerebrospinal fluid”, “SARS-CoV-2 and CNS Complication”.Results: We performed CSF analysis results in total of 113 patients from 67 papers. There were 7 patients out of 113 patients (6.2 %) were fatal and 35 patients (31 %) were considered severe and rest non-severe. Elevated cell counts (>5 cells/µL) were found in 43% (3/7) of the fatal cases, 25.7% (9/35) of the severe cases and 29.4% (15/51) of non-severe cases. The average CSF protein of 110.0 mg/dl found in fatal, and in 85.4mg/dl in non-fatal cases. Whereas, average CSF protein levels were 78 mg/dl in severe and 103 mg/dl in non-severe cases. In addition, 76.5% (13/17) of the patients with CNS complications and 74.1% (40/54) of the patients with a PNS manifestation showed elevated protein levels.Conclusion: The most common finding of CSF analysis in the setting of neurological manifestations in Covid-19 is noted to be elevated CSF protein with occasionally elevated, predominantly lymphocytic cell count. Interestingly, CSF protein is noted to be majorly elevated in all spectrums of severity of neurological illness including CNS and PNS complications. This may be indicative of only one common pathophysiological mechanism of neurological illness. In future, A combination of SARS-CoV-2 CSF RT-PCR, CSF IgM testing, and CNS targeting antibodies should be further studied to understand pathophysiology of neurological complications in Covid-19.

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Neurological Manifestations and Complications of Coronavirus Disease 2019 (COVID-19): A Systematic Review and Meta-Analysis

10.21203/rs.3.rs-39952/v1 ◽

2020 ◽

Author(s):

Ahmed Yassin ◽

Mohammed Nawaiseh ◽

Ala' Shaban ◽

Khalid Alsherbini ◽

Khalid El-Salem ◽

...

Keyword(s):

Systematic Review ◽

English Language ◽

Early Recognition ◽

Case Reports ◽

Meta Analysis ◽

Age Groups ◽

Cerebrovascular Diseases ◽

Neurological Involvement ◽

Neurological Manifestations ◽

Summary Estimate

Abstract Background: The spectrum of neurological involvement in COVID-19 is not thoroughly understood. To the best of our knowledge, no systematic review with meta-analysis and a sub-group comparison between severe and non-severe cases has been published. The aim of this study is to assess the frequency of neurological manifestations and complications, identify the neurodiagnostic findings, and compare these aspects between severe and non-severe COVID-19 cases.Methods: A systematic search of PubMed, Scopus, EBSCO, Web of Science, and Google Scholar databases was conducted for studies published between the 1st of January 2020 and 22nd of April 2020. In addition, we scanned the bibliography of included studies to identify other potentially eligible studies. The criteria for eligibility included studies published in English language (or translated to English), those involving patients with COVID-19 of all age groups, and reporting neurological findings. Data were extracted from eligible studies. Meta-analyses were conducted using comprehensive meta-analysis software. Random-effects model was used to calculate the pooled percentages and means with their 95% confidence intervals (CIs). Sensitivity analysis was performed to assess the effect of individual studies on the summary estimate. A subgroup analysis was conducted according to severity. The main outcomes of the study were to identify the frequency and nature of neurological manifestations and complications, and the neuro-diagnostic findings in COVID-19 patients.Results: 44 articles were included with a pooled sample size of 13480 patients. The mean age was 50.3 years and 53% were males. The most common neurological manifestations were: Myalgia (22.2%, 95% CI, 17.2% to 28.1%), taste impairment (19.6%, 95% CI, 3.8% to 60.1%), smell impairment (18.3%, 95% CI, 15.4% to 76.2%), headache (12.1%, 95% CI, 9.1% to 15.8%), dizziness (11.3%, 95% CI, 8.5% to 15.0%), and encephalopathy (9.4%, 95% CI, 2.8% to 26.6%). Nearly 2.5% (95% CI, 1% to 6.1%) of patients had acute cerebrovascular diseases (CVD). Myalgia, elevated CK and LDH, and acute CVD were significantly more common in severe cases. Moreover, 20 case reports were assessed qualitatively, and their data presented separately.Conclusions: Neurological involvement is common in COVID-19 patients. Early recognition and vigilance of such involvement might impact their overall outcomes.

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Neurological manifestations and complications of coronavirus disease 2019 (COVID-19): a systematic review and meta-analysis

BMC Neurology ◽

10.1186/s12883-021-02161-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ahmed Yassin ◽

Mohammed Nawaiseh ◽

Ala Shaban ◽

Khalid Alsherbini ◽

Khalid El-Salem ◽

...

Keyword(s):

Systematic Review ◽

English Language ◽

Early Recognition ◽

Case Reports ◽

Meta Analysis ◽

Age Groups ◽

Cerebrovascular Diseases ◽

Neurological Involvement ◽

Neurological Manifestations ◽

Summary Estimate

Abstract Background The spectrum of neurological involvement in COVID-19 is not thoroughly understood. To the best of our knowledge, no systematic review with meta-analysis and a sub-group comparison between severe and non-severe cases has been published. The aim of this study is to assess the frequency of neurological manifestations and complications, identify the neurodiagnostic findings, and compare these aspects between severe and non-severe COVID-19 cases. Methods A systematic search of PubMed, Scopus, EBSCO, Web of Science, and Google Scholar databases was conducted for studies published between the 1st of January 2020 and 22nd of April 2020. In addition, we scanned the bibliography of included studies to identify other potentially eligible studies. The criteria for eligibility included studies published in English language (or translated to English), those involving patients with COVID-19 of all age groups, and reporting neurological findings. Data were extracted from eligible studies. Meta-analyses were conducted using comprehensive meta-analysis software. Random-effects model was used to calculate the pooled percentages and means with their 95% confidence intervals (CIs). Sensitivity analysis was performed to assess the effect of individual studies on the summary estimate. A subgroup analysis was conducted according to severity. The main outcomes of the study were to identify the frequency and nature of neurological manifestations and complications, and the neuro-diagnostic findings in COVID-19 patients. Results 44 articles were included with a pooled sample size of 13,480 patients. The mean age was 50.3 years and 53% were males. The most common neurological manifestations were: Myalgia (22.2, 95% CI, 17.2 to 28.1%), taste impairment (19.6, 95% CI, 3.8 to 60.1%), smell impairment (18.3, 95% CI, 15.4 to 76.2%), headache (12.1, 95% CI, 9.1 to 15.8%), dizziness (11.3, 95% CI, 8.5 to 15.0%), and encephalopathy (9.4, 95% CI, 2.8 to 26.6%). Nearly 2.5% (95% CI, 1 to 6.1%) of patients had acute cerebrovascular diseases (CVD). Myalgia, elevated CK and LDH, and acute CVD were significantly more common in severe cases. Moreover, 20 case reports were assessed qualitatively, and their data presented separately. Conclusions Neurological involvement is common in COVID-19 patients. Early recognition and vigilance of such involvement might impact their overall outcomes.

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Use of Antioxidants for the Neuro-Therapeutic Management of COVID-19

Antioxidants ◽

10.3390/antiox10060971 ◽

2021 ◽

Vol 10 (6) ◽

pp. 971

Author(s):

Noemí Cárdenas-Rodríguez ◽

Cindy Bandala ◽

América Vanoye-Carlo ◽

Iván Ignacio-Mejía ◽

Saúl Gómez-Manzo ◽

...

Keyword(s):

Neuromuscular Junctions ◽

Cardiac Injury ◽

Clinical Manifestations ◽

Specific Treatment ◽

Kidney Injury ◽

Neurological Complications ◽

Neurological Manifestations ◽

Systemic Complications ◽

The Central Nervous System ◽

Brain Tissue Damage

Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is an emergent infectious disease that has caused millions of deaths throughout the world. COVID-19 infection’s main symptoms are fever, cough, fatigue, and neurological manifestations such as headache, myalgias, anosmia, ageusia, impaired consciousness, seizures, and even neuromuscular junctions’ disorders. In addition, it is known that this disease causes a series of systemic complications such as adverse respiratory distress syndrome, cardiac injury, acute kidney injury, and liver dysfunction. Due to the neurological symptoms associated with COVID-19, damage in the central nervous system has been suggested as well as the neuroinvasive potential of SARS-CoV-2. It is known that CoV infections are associated with an inflammation process related to the imbalance of the antioxidant system; cellular changes caused by oxidative stress contribute to brain tissue damage. Although anti-COVID-19 vaccines are under development, there is no specific treatment for COVID-19 and its clinical manifestations and complications; only supportive treatments with immunomodulators, anti-vascular endothelial growth factors, modulating drugs, statins, or nutritional supplements have been used. In the present work, we analyzed the potential of antioxidants as adjuvants for the treatment of COVID-19 and specifically their possible role in preventing or decreasing the neurological manifestations and neurological complications present in the disease.

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Neurological aspects of COVID-19

Kazan medical journal ◽

10.17816/kmj2021-877 ◽

2021 ◽

Vol 102 (6) ◽

pp. 877-886

Author(s):

M B Aliyeva ◽

S S Saparbayev ◽

D N Ayaganov ◽

M S Kurmangazin ◽

N M Tuychibaeva

Keyword(s):

Neurological Disorders ◽

Neurological Complications ◽

Neurological Manifestations ◽

Hypoxemic Respiratory Failure ◽

Systemic Complications ◽

Central Nervous System Damage ◽

Neuropsychiatric Complications ◽

Taste Disorders ◽

Hepatic Lesions ◽

The City

The coronavirus disease COVID-19 began to spread worldwide in December 2019 from the city of Wuhan (China). COVID-19 is often accompanied by fever, hypoxemic respiratory failure and systemic complications (for example, gastrointestinal, renal, cardiac, neurological, and hepatic lesions), thrombotic phenomena. Central nervous system damage is caused by the primary effect on it, direct neuroinvasion of the virus, and more often by secondary effect due to systemic hyperinflammation. Neurological manifestations include fatigue, headache, insomnia, and olfactory/taste disorders. Neurological manifestations and complications of COVID-19 are diverse: (1) cerebral circulatory disorders, including ischemic stroke and macro/microhemorrhages; (2) encephalopathy; (3) para/postinfectious autoimmune complications, such as GuillainBarre syndrome; (4) meningoencephalitis; (5) neuropsychiatric complications (psychosis and mood disorders). In terms of pathogenesis, neurological disorders in COVID-19 can be caused by neurotropicity and neurovirulence of SARS-CoV-2, cytokine storm, hypoxemia, homeostasis disorders, as well as their combined effects. COVID-19 adversely affects the course and prognosis of chronic neurological disorders in comorbid patients. The review highlights the need for vigilance to early neurological complications in patients infected with SARS-CoV-2 and other coronaviruses, especially since some neurological complications may precede respiratory manifestations.

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Neurological manifestations of coronavirus infections: a systematic review

10.1101/2020.08.26.20182196 ◽

2020 ◽

Author(s):

Jesper Almqvist ◽

Tobias Granberg ◽

Antonios Tzortzakakis ◽

Stefanos Klironomos ◽

Evangelia Kollia ◽

...

Keyword(s):

Systematic Review ◽

Cerebrovascular Disorders ◽

Acute Disseminated Encephalomyelitis ◽

Neurological Complications ◽

Diagnostic Workup ◽

Neurological Manifestations ◽

Chronic Disability ◽

Neuropsychiatric Complications ◽

Immune Mediated ◽

Depth Analysis

In order to optimize diagnostic workup of the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, we systematically reviewed neurological and neuroradiological manifestations of SARS-CoV-2 and all other known human coronavirus species (HCoV). Which lessons can we learn? We identified relevant publications (until July 26h 2020) using systematic searches in PubMed, Web of Science and Ovid EMBASE with predefined search strings. A total of 4571 unique publications were retrieved, out of which 378 publications were selected for in-depth analysis by two raters, including a total of 17549 (out of which were 14418 SARS-CoV-2) patients. Neurological complications and associated neuroradiological manifestations are prevalent for all HCoVs (HCoV-229E, HKU1, NL63, OC43, Middle East respiratory syndrome (MERS)-CoV, SARS-CoV-1 and SARS-CoV-2). Moreover, there are similarities in symptomatology across different HCoVs, particularly between SARS-CoV-1 and SARS-CoV-2. Common neurological manifestations include fatigue, headache and smell/taste disorders. Additionally, clinicians need to be attentive for at least five classes of neurological complications: (1) Cerebrovascular disorders including ischemic stroke and macro/micro-hemorrhages, (2) encephalopathies, (3) para-/postinfectious immune-mediated complications such as Guillain-Barre syndrome and acute disseminated encephalomyelitis, (4) (meningo-)encephalitis, potentially with concomitant seizures and (5) neuropsychiatric complications such as psychosis and mood disorders. Our systematic review highlights the need for vigilance regarding neurological complications in patients infected by SARS-CoV-2 and other HCoVs, especially since some complications may result in chronic disability. Neuroimaging protocols should be designed to specifically screen for these complications. Therefore, we propose practical imaging guidelines to facilitate the diagnostic workup and monitoring of patients infected with HCoVs.

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