Mild to Severe Neurological Manifestations of COVID-19: Cases Reports

The main focus of Coronavirus disease 2019 (COVID-19) infection is pulmonary complications through virus-related neurological manifestations, ranging from mild to severe, such as encephalitis, cerebral thrombosis, neurocognitive (dementia-like) syndrome, and delirium. The hospital screening procedures for quickly recognizing neurological manifestations of COVID-19 are often complicated by other coexisting symptoms and can be obscured by the deep sedation procedures required for critically ill patients. Here, we present two different case-reports of COVID-19 patients, describing neurological complications, diagnostic imaging such as olfactory bulb damage (a mild and unclear underestimated complication) and a severe and sudden thrombotic stroke complicated with hemorrhage with a low-level cytokine storm and respiratory symptom resolution. We discuss the possible mechanisms of virus entrance, together with the causes of COVID-19-related encephalitis, olfactory bulb damage, ischemic stroke, and intracranial hemorrhage.

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Relevance and Clinical Significance of Magnetic Resonance Imaging of Neurological Manifestations in COVID-19: A Systematic Review of Case Reports and Case Series

Brain Sciences ◽

10.3390/brainsci10121017 ◽

2020 ◽

Vol 10 (12) ◽

pp. 1017

Author(s):

Anisa Chowdhary ◽

Roshan Subedi ◽

Medha Tandon ◽

Sijin Wen ◽

Jenil Patel ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Ischemic Stroke ◽

Magnetic Resonance ◽

Case Reports ◽

Case Series ◽

Neurological Complications ◽

Inflammatory Disorder ◽

Neurological Manifestations ◽

Resonance Imaging ◽

Mri Findings

We performed a systematic literature review of neuroimaging, predominantly focusing on magnetic resonance imaging (MRI) findings associated with neurological manifestations of coronavirus disease-2019 (COVID-19). We screened articles from PubMed, Google Scholar and Scopus, looking for reports that would potentially have neuroimaging findings in patients with COVID-19. Data analysis was performed with patient-based data based on the availability of clinical characteristics and outcomes for each individual patient from the studies. Chi square and Wilcoxon rank-sum tests were used to report COVID-19 severity and outcomes based on neurological imaging indicators and pathophysiology. A total of 171 patients with COVID-19 having neurological complications, from 134 studies, were identified in our review. The most common neuroimaging finding was ischemic stroke (62, 36.2%) cases, followed by CNS inflammatory disorder (44, 25.7%), and hemorrhagic stroke (41, 24.0%). Around 51% of all the fatal COVID-19 cases had an ischemic stroke. Among patients with ischemic stroke, the mean age of those who suffered from COVID-19 infection was 57.5 years (SD = 15.4) whereas it was 50.7 years (SD = 15.1) among those without stroke/other diagnosis. Fatality was more common in patients with ischemic stroke compared to those with other diagnosis (40% vs. 22%, p = 0.011). The most frequently published neuroimaging findings in patients with COVID-19 were ischemic stroke, CNS inflammatory disorder, and hemorrhagic disorder. In those studies, ischemic stroke was associated with fatality, and was more frequently seen in older patients. Based on our findings, early usage of MRI in COVID-19 patients may be recommended.

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Neurological symptoms, manifestations, and complications associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 19 (COVID-19)

Journal of Neurology ◽

10.1007/s00415-021-10406-y ◽

2021 ◽

Author(s):

Biyan Nathanael Harapan ◽

Hyeon Joo Yoo

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Case Reports ◽

Case Series ◽

Altered Mental Status ◽

Neurological Complications ◽

Neurological Symptoms ◽

Neurological Manifestations ◽

Fisher Syndrome ◽

Novel Coronavirus ◽

The Impact

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, is responsible for the outbreak of coronavirus disease 19 (COVID-19) and was first identified in Wuhan, China in December 2019. It is evident that the COVID-19 pandemic has become a challenging world issue. Although most COVID-19 patients primarily develop respiratory symptoms, an increasing number of neurological symptoms and manifestations associated with COVID-19 have been observed. In this narrative review, we elaborate on proposed neurotropic mechanisms and various neurological symptoms, manifestations, and complications of COVID-19 reported in the present literature. For this purpose, a review of all current published literature (studies, case reports, case series, reviews, editorials, and other articles) was conducted and neurological sequelae of COVID-19 were summarized. Essential and common neurological symptoms including gustatory and olfactory dysfunctions, myalgia, headache, altered mental status, confusion, delirium, and dizziness are presented separately in sections. Moreover, neurological manifestations and complications that are of great concern such as stroke, cerebral (sinus) venous thrombosis, seizures, meningoencephalitis, Guillain–Barré syndrome, Miller Fisher syndrome, acute myelitis, and posterior reversible encephalopathy syndrome (PRES) are also addressed systematically. Future studies that examine the impact of neurological symptoms and manifestations on the course of the disease are needed to further clarify and assess the link between neurological complications and the clinical outcome of patients with COVID-19. To limit long-term consequences, it is crucial that healthcare professionals can early detect possible neurological symptoms and are well versed in the increasingly common neurological manifestations and complications of COVID-19.

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Neurological Involvement in COVID-19

10.5772/intechopen.99309 ◽

2021 ◽

Author(s):

Valentina Opancina ◽

Kristijan Krstic ◽

Predrag Sazdanovic ◽

Nebojsa Zdravkovic ◽

Ruzica Radojevic Marjanovic ◽

...

Keyword(s):

Indirect Effects ◽

Case Reports ◽

Experimental Studies ◽

Neurological Complications ◽

Neurological Involvement ◽

Neurological Manifestations ◽

Neural Tissues ◽

Neurological Conditions ◽

The Brain ◽

Common Target

The respiratory system is the most common target of COVID-19, however, various experimental studies and case reports have shown its affinity for neural tissues. In this chapter, we described pathogenesis and propagation of SARS-CoV-2 virus in the nervous system, potential routes of the SARS-CoV-2 invasion in the brain, as well as indirect effects of COVID-19 on multiorgan disorders. We have also presented all of the reported neurological manifestations in COVID-19 with an explanation of possible underlying pathways. Among patients who tested positive on SARS-CoV-2, various neurological irregularities have been described, affecting both the central and peripheral nervous systems. In general, neurological complications in COVID-19 patients occur within 1 and 14 days, in most cases on average on the 5th day of the incubation period. We have demonstrated all of the reported neurological findings, whereas the most commonly reported were headache, dizziness, myalgia, hypogeusia, hyposmia, and impaired consciousness. More serious neurological conditions in COVID-19 included meningitis, encephalitis, and ischemic or hemorrhagic stroke.

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Neurological Manifestations of Coronavirus Disease 2019: A Comprehensive Review and Meta-Analysis of the First 6 Months of Pandemic Reporting

Frontiers in Neurology ◽

10.3389/fneur.2021.664599 ◽

2021 ◽

Vol 12 ◽

Author(s):

Samuel F. Huth ◽

Sung-Min Cho ◽

Chiara Robba ◽

David Highton ◽

Denise Battaglini ◽

...

Keyword(s):

Nervous System ◽

Ischemic Stroke ◽

Case Reports ◽

Meta Analysis ◽

Neurological Complications ◽

Residual Effects ◽

Resource Utilisation ◽

Neurologic Manifestations ◽

Case Definitions ◽

Neurologic Sequelae

Background: There is growing evidence that SARS-Cov-2 infection is associated with severe neurological complications. Understanding the nature and prevalence of these neurologic manifestations is essential for identifying higher-risk patients and projecting demand for ongoing resource utilisation. This review and meta-analysis report the neurologic manifestations identified in hospitalised COVID-19 patients and provide a preliminary estimate of disease prevalence.Methods: MEDLINE, Embase and Scopus were searched for studies reporting the occurrence of neurological complications in hospitalised COVID-19 patients.Results: A total of 2,207 unique entries were identified and screened, among which 14 cohort studies and 53 case reports were included, reporting on a total of 8,577 patients. Central nervous system manifestations included ischemic stroke (n = 226), delirium (n = 79), intracranial haemorrhage (ICH, n = 57), meningoencephalitis (n = 13), seizures (n = 3), and acute demyelinating encephalitis (n = 2). Peripheral nervous system manifestations included Guillain-Barrè Syndrome (n = 21) and other peripheral neuropathies (n = 3). The pooled period prevalence of ischemic stroke from identified studies was 1.3% [95%CI: 0.9–1.8%, 102/7,715] in all hospitalised COVID-19 patients, and 2.8% [95%CI: 1.0–4.6%, 9/318] among COVID-19 patients admitted to ICU. The pooled prevalence of ICH was estimated at 0.4% [95%CI: 0–0.8%, 6/1,006].Conclusions: The COVID-19 pandemic exerts a substantial neurologic burden which may have residual effects on patients and healthcare systems for years. Low quality evidence impedes the ability to accurately predict the magnitude of this burden. Robust studies with standardised screening and case definitions are required to improve understanding of this disease and optimise treatment of individuals at higher risk for neurologic sequelae.

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Spontaneous osteoporotic fractures of the sacrum causing neurological damage

Journal of Neurosurgery Spine ◽

10.3171/spi.2002.97.3.0380 ◽

2002 ◽

Vol 97 (3) ◽

pp. 380-385 ◽

Cited By ~ 3

Author(s):

Pierre-Jacques Finiels ◽

Hélène Finiels ◽

Denise Strubel ◽

Jean-Marc Jacquot

Keyword(s):

Elderly Women ◽

Case Reports ◽

Osteoporotic Fractures ◽

Neurological Complications ◽

Neurological Manifestations ◽

Neurological Damage ◽

Content Type ◽

True Incidence ◽

Multiple Health ◽

Fine Print

✓ Although osteoporotic fractures of the sacrum seem to be a well-known entity, their associated rate of neurological complications has not been assessed in the literature. The authors report three such cases of nerve root compromise in elderly women and conduct a literature review. Based on their review, they estimate the incidence to be approximately 2%. The true incidence is probably higher because many case reports provide only scant information on symptoms; furthermore, sphincter dysfunction and lower-limb paresthesias are the most common symptoms and can readily be overlooked or misinterpreted in elderly patients with multiple health problems. The neurological manifestations were delayed in some cases. A full recovery is the rule. The characteristics of the sacral fracture are not consistently related with the risk of neurological compromise. In most reviewed cases the authors found no displacement and in many the foramina were not involved. The pathophysiology of the neurological manifestations remains unclear. The authors suggest that patients with sacral osteoporotic fractures should be carefully monitored for neurological manifestations.

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SARS-CoV-2 Induced Neurological Manifestations Entangles Cytokine Storm That Implicates For Therapeutic Strategies

Current Medicinal Chemistry ◽

10.2174/0929867328666210506161543 ◽

2021 ◽

Vol 28 ◽

Author(s):

Zhao-Zhong Chong ◽

Nizar Souayah

Keyword(s):

Nervous System ◽

Immune Responses ◽

Neurological Complications ◽

Therapeutic Strategies ◽

Neurological Symptoms ◽

The Novel ◽

Cytokine Storm ◽

Neurological Manifestations ◽

Direct Invasion ◽

Insight Into

Abstract: The new coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can present with neurological symptoms and induce neurological complications. The involvement in both the central and peripheral nervous systems in COVID-19 patients has been associated with direct invasion of the virus and the induction of cytokine storm. This review discussed the pathways for the virus invasion into the nervous system and characterized the SARS-CoV-2 induced cytokine storm. In addition, the mechanisms underlying the immune responses and cytokine storm induction after SARS-CoV-2 infection were also discussed. Although some neurological symptoms are mild and disappear after recovery from infection, some severe neurological complications contribute to the mortality of COVID-19 patients. Therefore, the insight into the cause of SARS-CoV-2 induced cytokine storm in context with neurological complications will formulate the novel management of the disease and further identify new therapeutic targets for COVID-19.

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COVID-19 and neuroinvasion: a systematic review

10.5327/1516-3180.747 ◽

2021 ◽

Author(s):

Alícia Malta Brandão Nunes

Keyword(s):

Olfactory Bulb ◽

Wide Spectrum ◽

Cytokine Storm ◽

Neurological Manifestations ◽

Inclusion Criteria ◽

Medical Databases ◽

Direct Invasion ◽

Randomized Clinical Study ◽

Study Results ◽

Ace2 Gene

Background: Clinical practice throughout the pandemic has generated a debate about the existence of neurotropism and the neuropathogenic capacity of the new coronavirus. Medical professionals have noted that there is a wide spectrum of neurological manifestations associated with SARS-CoV-2 infections; from hyposmia to encephalopathy. The interaction of the viral protein spike (S) with the ACE2 gene present in endothelial and nerve cells and the cytokine storm triggered by COVID-19 are explanatory bases for a series of mechanisms proposed in recent literature. Objectives: To establish a direct connection, or not, between neurological manifestations and SARS-CoV-2 infection. Design and setting: Analysis of the current literature present in medical databases. Methods: To select the studies, the Medline (Pubmed), LILACS and SciELO databases were used with the keywords “neurology” and “covid” and “mechanism”. The search period for the articles covered the last 10 months (since June 2020). The selection and design criteria of the studies were descriptive, crosssectional, cohort, case report and randomized clinical study. Results: Thirty-eight articles with potential for inclusion were retrieved, but only seventeen of them declared no conflict of interest and answered the inclusion criteria and the guiding question, which consisted of assessing the association between neurological disorders and COVID-19. Conclusion: Eight studies defend the indirect invasion, due to the imaging exams presenting an olfactory bulb without any alteration. Through infection of the endothelial cells, vascular alterations and wear of the BBB by the cytokine storm. In parallel, the other nine studies advocate direct invasion, where the virus infects the olfactory bulb and reaches the rhinencephalon and midbrain through the axons, generating, for example, the lack of symptoms in the so-called happy hypoxia of the coronavirus. Neuroinvasion in COVID-19 is still unclear, but hypotheses show 2 possible pathways for the virus to access the CNS: hematogenous and retrograde neuronal pathways. To elucidate these pathogenic pathways, larger and more systematic studies will be needed.

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Neurological Complications of SARS-CoV-2 Infection in Children: A Systematic Review and Meta-Analysis

Journal of Tropical Pediatrics ◽

10.1093/tropej/fmaa070 ◽

2020 ◽

Cited By ~ 1

Author(s):

Prateek Kumar Panda ◽

Indar Kumar Sharawat ◽

Pragnya Panda ◽

Vivekanand Natarajan ◽

Rahul Bhakat ◽

...

Keyword(s):

Systematic Review ◽

Case Reports ◽

Meta Analysis ◽

Random Effect ◽

Case Series ◽

Neurological Complications ◽

Severe Illness ◽

Neurological Manifestations ◽

Eligibility Criteria ◽

Symptomatic Seizures

Abstract Background Knowledge about neurological complications of COVID-19 in children is limited due to the paucity of data in the existing literature. Some systematic reviews are available describing overall clinical features of COVID-19 in children and neurological complications of COVID-19 in adults. But to the best of our knowledge, no systematic review has been performed to determine neurological manifestations of COVID-19. Methods Six different electronic databases (MEDLINE, EMBASE, Web of Science, CENTRAL, medRxiv and bioRxiv) were searched for articles related to COVID-19 and neurological complications in children. Studies/case series reporting neurological manifestations of COVID-19 in patients aged ≤18 years, as well as case reports, as neurological complications appear to be rare. The pooled estimate of various non-specific and specific neurological manifestations was performed using a random effect meta-analysis. Results Twenty-one studies/case series and five case reports (3707 patients) fulfilled the eligibility criteria and were included in this systematic review, from a total of 460 records. Headache, myalgia and fatigue were predominant non-specific neurological manifestations, presenting altogether in 16.7% cases. Total of 42 children (1%) were found to have been reported with definite neurological complications, more in those suffering from a severe illness (encephalopathy—25, seizure—12, meningeal signs—17). Rare neurological complications were intracranial hemorrhage, cranial nerve palsy, Guillain–Barré syndrome and vision problems. All children with acute symptomatic seizures survived suggesting a favorable short-term prognosis. Conclusion Neurological complications are rare in children suffering from COVID-19. Still, these children are at risk of developing seizures and encephalopathy, more in those suffering from severe illness.

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Neurological manifestations and implications of COVID-19 pandemic

Therapeutic Advances in Neurological Disorders ◽

10.1177/1756286420932036 ◽

2020 ◽

Vol 13 ◽

pp. 175628642093203 ◽

Cited By ~ 21

Author(s):

Georgios Tsivgoulis ◽

Lina Palaiodimou ◽

Aristeidis H. Katsanos ◽

Valeria Caso ◽

Martin Köhrmann ◽

...

Keyword(s):

Care Delivery ◽

Neurological Diseases ◽

Case Reports ◽

Case Series ◽

Relevant Information ◽

Healthcare Services ◽

Neurological Complications ◽

Cerebrovascular Diseases ◽

Neurological Manifestations ◽

Stroke Risk Factor

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China and rapidly spread worldwide, with a vast majority of confirmed cases presenting with respiratory symptoms. Potential neurological manifestations and their pathophysiological mechanisms have not been thoroughly established. In this narrative review, we sought to present the neurological manifestations associated with coronavirus disease 2019 (COVID-19). Case reports, case series, editorials, reviews, case-control and cohort studies were evaluated, and relevant information was abstracted. Various reports of neurological manifestations of previous coronavirus epidemics provide a roadmap regarding potential neurological complications of COVID-19, due to many shared characteristics between these viruses and SARS-CoV-2. Studies from the current pandemic are accumulating and report COVID-19 patients presenting with dizziness, headache, myalgias, hypogeusia and hyposmia, but also with more serious manifestations including polyneuropathy, myositis, cerebrovascular diseases, encephalitis and encephalopathy. However, discrimination between causal relationship and incidental comorbidity is often difficult. Severe COVID-19 shares common risk factors with cerebrovascular diseases, and it is currently unclear whether the infection per se represents an independent stroke risk factor. Regardless of any direct or indirect neurological manifestations, the COVID-19 pandemic has a huge impact on the management of neurological patients, whether infected or not. In particular, the majority of stroke services worldwide have been negatively influenced in terms of care delivery and fear to access healthcare services. The effect on healthcare quality in the field of other neurological diseases is additionally evaluated.

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Neurological Manifestations of Patients Infected with COVID-19: A Systematic Review

Austin Journal of Neurological Disorders & Epilepsy ◽

10.26420/austinjneuroldisordepilepsy.2021.1046 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Jafari N ◽

◽

Khoshghamat N ◽

Ghaderi MS ◽

Yazdani S ◽

...

Keyword(s):

Nervous System ◽

Case Reports ◽

Cerebrovascular Disorders ◽

Case Series ◽

Neurological Complications ◽

Observational Research ◽

Neurological Manifestations ◽

Qualitative Synthesis ◽

Systematic Analysis ◽

Fisher Syndrome

In the light of the recent evidence, neurological manifestations have been reported in patients infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). To shed light on a clear-cut explanation of neurological complications followed by SARS-CoV-2, a systematic analysis was reviewed. To this point, general medical databases, such as PubMed, Scopus, and Google Scholar from January 1, 2020, to September 20, 2020, were systematically searched to find related published articles. Through the search strategy, 93 studies for qualitative synthesis were included. Finally, the available data of 8,753 hospitalized patients with coronavirus disease 2019 (COVID-19) showed that the most prevalent Central Nervous System (CNS) manifestations of COVID-19 were headache (1137 cases, 18%) and dizziness (142 cases, 2%). On the other hand, some peripheral nervous system (PNS) symptoms were muscle pain (3300 cases, 53%), hypogeusia (646 cases, 11%), anosmia (545 cases, 9%), and hyposmia (379 cases, 6%). Furthermore, a small proportion of patients had ageusia (74 cases, 1%), cerebrovascular disorders (66 cases, 0.75%), and impaired consciousness (21 cases, 0.2%). Besides, some neurological features, such as encephalitis, neuralgia, ataxia, Guillain- Barre syndrome, miller fisher syndrome, intracerebral hemorrhage, polyneuritis cranialis, and dystonic posture were reported in the literature as case reports and case series. Conclusion: Taken together, data from our systematic analysis indicated that neurological manifestations in both CNS and PNS were reported in COVID-19 patients. Further observational research in this field with more participants are needed to detect the specific risk concerning neurological complications in COVID-19 infection.

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