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

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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What can the neurological manifestations of COVID-19 tell us: a meta-analysis

Journal of Translational Medicine ◽

10.1186/s12967-021-03039-2 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Yuanyuan He ◽

Xiaojie Bai ◽

Tiantian Zhu ◽

Jialin Huang ◽

Hong Zhang

Keyword(s):

Nervous System ◽

English Literature ◽

Meta Analysis ◽

Altered Mental Status ◽

Neurological Complications ◽

Neurological Symptoms ◽

Cochrane Library ◽

Neurological Manifestations ◽

Global Pandemic ◽

The Future

Abstract Background Covid-19 became a global pandemic in 2019. Studies have shown that coronavirus can cause neurological symptoms, but clinical studies on its neurological symptoms are limited. In this meta-analysis, we aimed to summarize the various neurological manifestations that occurred in COVID-19 patients and calculate the incidence of various neurological manifestations. At the same time, we further explored the mechanism of nervous system injury and prognosis in COVID-19 patients in combination with their nervous system manifestations. This study provides a reference for early clinical identification of COVID-19 nervous system injury in the future, so as to achieve early treatment and reduce neurological sequelae. Methods We systematically searched all published English literature related to the neurological manifestations of COVID-19 from January 1, 2020, to April 30, 2021, in Pubmed, Embase, and Cochrane Library. The keywords used were COVID-19 and terminology related to the nervous system performance. All included studies were selected by two independent reviewers using EndNote and NoteExpress software, any disagreement was resolved by consensus or by a third reviewer, and the selected data were then collected for meta-analysis using a random-effects model. Results A total of 168 articles (n = 292,693) were included in the study, and the meta-analysis showed that the most common neurological manifestations of COVID-19 were myalgia(33%; 95%CI 0.30–0.37; I2 = 99.17%), smell impairment(33%; 95%CI 0.28–0.38; I2 = 99.40%), taste dysfunction(33%; 95%CI 0.27–0.39; I2 = 99.09%), altered mental status(32%; 95%CI 0.22–0.43; I2 = 99.06%), headache(29%; 95%CI 0.25–0.33; I2 = 99.42%), encephalopathy(26%; 95%CI 0.16–0.38; I2 = 99.31%), alteration of consciousness(13%; 95%CI 0.08–0.19; I2 = 98.10%), stroke(12%; 95%CI 0.08–0.16; I2 = 98.95%), dizziness(10%; 95%CI 0.08–0.13; I2 = 96.45%), vision impairment(6%; 95%CI 0.03–0.09; I2 = 86.82%), intracerebral haemorrhage(5%; 95%CI 0.03–0.09; I2 = 95.60%), seizure(4%; 95%CI 0.02 -0.05; I2 = 98.15%), encephalitis(2%; 95%CI 0.01–0.03; I2 = 90.36%), Guillan-Barré Syndrome (GBS) (1%; 95%CI 0.00–0.03; I2 = 89.48%). Conclusions Neurological symptoms are common and varied in Covid-19 infections, and a growing number of reports suggest that the prevalence of neurological symptoms may be increasing. In the future, the role of COVID-19 neurological symptoms in the progression of COVID-19 should be further studied, and its pathogenesis and assessment methods should be explored, to detect and treat early neurological complications of COVID-19 and reduce mortality.

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What can the neurological manifestations of COVID-19 tell us : a meta-analysis

10.21203/rs.3.rs-284876/v1 ◽

2021 ◽

Author(s):

Yuanyuan He ◽

Xiaojie Bai ◽

Tiantian Zhu ◽

Jialin Huang ◽

Hong Zhang

Keyword(s):

Nervous System ◽

English Literature ◽

Meta Analysis ◽

Damage Mechanism ◽

Altered Mental Status ◽

Neurological Complications ◽

Neurological Symptoms ◽

Neurological Manifestations ◽

Global Pandemic ◽

Taste Dysfunction

Abstract Background Covid-19 became a global pandemic in 2019. Studies have shown that coronavirus can cause neurological symptoms, but clinical studies on its neurological symptoms are limited. In this meta-analysis, we aim to gather and discuss COVID-19 various neurological symptoms of infection, and to assess the prevalence of each of the nervous system symptoms, and characterized by neurological in-depth discussions of nervous system damage mechanism, biomarkers and inspection methods, recovery and prognosis, and provide the research behind the potential target and direction. Methods We systematically searched all published English literature related to the neurological manifestations of COVID-19 from January 1, 2020 to November 20, 2020 in Pubmed, Embase, and Cochrane library.The keywords used were COVID-19 and terminology related to nervous system performance.All included studies were selected by two independent reviewers using EndNote and NoteExpress software, any disagreement was resolved by consensus or by a third reviewer, and the selected data was then collected for meta-analysis using a random-effects model. Results A total of 62 articles (n =32729) were included in the study, and the meta-analysis showed that the most common neurological manifestations of COVID-19 were altered mental status (39% ; 95% CI 0.17-0.64 ; I 2 98.59%), encephalopathy (37% ; 95% CI 0.17-0.60 ; I 2 97.36%), myalgia(31% ; 95% CI 0.25-0.38; I 2 98.79%), headache(30% ; 95% CI 0.22-0.37; I 2 99.28%), smell impairment(28% ; 95% CI 99.57% ; I 2 0.17-0.39), taste dysfunction (27% ; 95% CI 0.18 -0.38 ; I 2 99.35%), acute ischemic stroke (23% ; 95% CI 0.06-0.47 ; I 2 99.30%), alteration of consciousness(17% ; 95% CI 0.06-0.31 ; I 2 96.78%), dizziness (10% ; 95% CI 0.06-0.15; I 2 95.30%), intracerebral haemorrhage (7% ; 95% CI 0.02-0.14 ; I 2 93.64%), vision impairment(5% ; 95% CI 0.02-0.10 ; I 2 92.73%), seizure(2% ; 95% CI 0.01-0.04 ; I 2 84.67%). Conclusions Neurological symptoms are common and varied in Covid-19 infections, and a growing number of reports suggest that the prevalence of neurological symptoms may be increasing. In the future, the role of COVID-19 neurological symptoms in the progression of COVID-19 should be further studied, and its pathogenesis and assessment methods should be explored, so as to detect and treat early neurological complications of COVID-19 and reduce mortality.

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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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SARS-CoV-2 and the Nervous System: From Clinical Features to Molecular Mechanisms

International Journal of Molecular Sciences ◽

10.3390/ijms21155475 ◽

2020 ◽

Vol 21 (15) ◽

pp. 5475 ◽

Cited By ~ 11

Author(s):

Manuela Pennisi ◽

Giuseppe Lanza ◽

Luca Falzone ◽

Francesco Fisicaro ◽

Raffaele Ferri ◽

...

Keyword(s):

Nervous System ◽

Molecular Mechanisms ◽

Neuronal Damage ◽

Neurological Complications ◽

Neurological Manifestations ◽

Wide Range ◽

Inflammatory State ◽

Acute Polyneuropathy ◽

The Central Nervous System ◽

The Impact

Increasing evidence suggests that Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2) can also invade the central nervous system (CNS). However, findings available on its neurological manifestations and their pathogenic mechanisms have not yet been systematically addressed. A literature search on neurological complications reported in patients with COVID-19 until June 2020 produced a total of 23 studies. Overall, these papers report that patients may exhibit a wide range of neurological manifestations, including encephalopathy, encephalitis, seizures, cerebrovascular events, acute polyneuropathy, headache, hypogeusia, and hyposmia, as well as some non-specific symptoms. Whether these features can be an indirect and unspecific consequence of the pulmonary disease or a generalized inflammatory state on the CNS remains to be determined; also, they may rather reflect direct SARS-CoV-2-related neuronal damage. Hematogenous versus transsynaptic propagation, the role of the angiotensin II converting enzyme receptor-2, the spread across the blood-brain barrier, the impact of the hyperimmune response (the so-called “cytokine storm”), and the possibility of virus persistence within some CNS resident cells are still debated. The different levels and severity of neurotropism and neurovirulence in patients with COVID-19 might be explained by a combination of viral and host factors and by their interaction.

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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 symptoms of COVID-19

Pharmacotherapy in Psychiatry and Neurology ◽

10.33450/fpn.2020.11.001 ◽

2021 ◽

Vol 36 (4) ◽

pp. 285-296

Author(s):

Adriana Wawer ◽

Agnieszka Piechal

Keyword(s):

Nervous System ◽

Viral Infections ◽

Harmful Effect ◽

Neurological Complications ◽

Neurological Symptoms ◽

Acute Respiratory Disease ◽

Neurological Damage ◽

Impaired Consciousness ◽

Potential Impact ◽

The Brain

Objective. Some viral infections can have a harmful effect on the functioning of the nervous system and can even cause serious neurological damage. This work aims to review the results of studies published so far concerning neurological complications in people infected with coronaviruses, especially SARS-CoV-2, and possible mechanisms responsible for nervous system damage. Literature review. Recently, there have been reports that coronaviruses, including SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), cause acute respiratory disease, exhibit neurotropic properties and can also cause neurological symptoms. There are studies published showing that these viruses may penetrate to the brain and cerebrospinal fluid. Conclusions. Coronaviruses are still poorly understood, so it seems important to study the potential impact of SARS-CoV-2 infections on the nervous system. It seems appropriate that patients infected with SARS-CoV-2 should be early evaluated for neurological symptoms, including headache and impaired consciousness.

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Argentine Registry of neurological manifestations due to coronavirus-19 (COVID-19)

10.1101/2021.03.19.21253558 ◽

2021 ◽

Author(s):

Mariana Bendersky ◽

Lucas Alessandro ◽

Franco Appiani ◽

Brenda Borrego Guerrero ◽

Patricia Cairola ◽

...

Keyword(s):

Demographic Variables ◽

Neurological Symptoms ◽

Neurological Manifestations ◽

Cns Involvement ◽

Term Care ◽

Cerebrovascular Complications ◽

Guillain Barré ◽

Neurological Pathology ◽

Degree Of Severity

COVID-19 disease has spread around the world since December 2019. Neurological symptoms are part of its clinical spectrum. Objective: To know the neurological manifestations in patients infected by COVID-19 in Argentina. Methods: Multicenter study conducted in adults, from May 2020 to January 2021, with confirmed COVID-19 and neurological symptoms. Demographic variables, existence of systemic or neurological comorbidities, the form of onset of the infection, alteration in complementary studies and the degree of severity of neurological symptoms were recorded. Results: 817 patients from all over the country were included, 52% male, mean age 38 years, most of them without comorbidities or previous neurological pathology. The first symptom of the infection was neurological in 56.2% of the cases, predominantly headache (69%), then anosmia / ageusia (66%). Myalgias (52%), allodynia / hyperalgesia (18%), and asthenia (6%) were also reported. 3.2% showed diffuse CNS involvement such as encephalopathy or seizures. 1.7% had cerebrovascular complications. Sleep disorders were observed in 3.2%. 6 patients were reported with Guillain Barre (GBS), peripheral neuropathy (3.4%), tongue paresthesia (0.6%), hearing loss (0.4%), plexopathy (0.3%). The severity of neurological symptoms was correlated with age and the existence of comorbidities. Conclusions: Our results, similar to those of other countries, show two types of neurological symptoms associated with COVID-19: some potentially disabling or fatal such as GBS or encephalitis, and others less devastating, but more frequent such as headache or anosmia that demand increasingly long-term care.

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The Incidence of SARS-COV-2 Manifestations in the Central Nervous System: A Rapid Review and Meta-Analysis

10.21203/rs.3.rs-44795/v1 ◽

2020 ◽

Author(s):

Verena Mayr ◽

Glechner Anna ◽

Gerald Gartlehner ◽

Irma Klerings ◽

Peter Lackner

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Cohort Studies ◽

Case Studies ◽

Data Extraction ◽

Meta Analysis ◽

Neurological Complications ◽

Rapid Review ◽

Current Evidence ◽

Treatment Team

Abstract Background: Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2 and presents itself mainly as a respiratory tract infection. However, reports of associated central nervous system (CNS) manifestations are increasing.Methods: We conducted this rapid review to determine the frequency of CNS manifestations of COVID-19 (CNS symptoms, acute cerebrovascular disease, and infectious/inflammatory CNS diseases) and to summarize the current evidence for direct invasion of the CNS by SARS-CoV-2. An information specialist searched Ovid MEDLINE, the CDC: COVID-19 Research Articles Downloadable and WHO COVID-19 Databases, CENTRAL, and Epistemonikos.org on May 13, 2020. Two reviewers screened abstracts and potentially relevant full-text publications independently. The data extraction, assessment of risk of bias,and certainty of evidence using GRADE was done by one reviewer and double-checked by another. If possible and reasonable, a meta-analysis was carried out.Results: We identified 13 relevant studies (four cohort studies, nine case studies) with a total of 866 COVID-19 patients.In a Chinese cohort, dizziness (16.8%; 36 of 214) and headache (13.1%; 28 of 214) were the most common CNS symptoms reported. A meta-analysis of four cohort studies including 851 COVID-19 patients showed an incidence of 3.3% (95% CI: 2.2–4.9) for ischemic stroke (follow-up: one to five weeks). In 13 of 15 encephalitis case studies, PCR testing of the cerebrospinal fluid did not detect any virus components.Conclusion: CNS manifestations occur frequently in patients with COVID-19. It is important to integrate neurologists into the multiprofessional COVID-19 treatment team to detect neurological complications early and to treat them correctly.

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Frequency and Severity of Central Nervous System Lesions in Hemophagocytic Lymphohistiocytosis

Blood ◽

10.1182/blood.v89.3.794 ◽

1997 ◽

Vol 89 (3) ◽

pp. 794-800 ◽

Cited By ~ 155

Author(s):

Elie Haddad ◽

Maria-Luisa Sulis ◽

Nada Jabado ◽

Stephane Blanche ◽

Alain Fischer ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Disease Progression ◽

Hemophagocytic Lymphohistiocytosis ◽

Systemic Disease ◽

Neurological Symptoms ◽

Treatment Modalities ◽

Remission Induction ◽

Cns Involvement ◽

Cns Disease

Abstract We have retrospectively assessed the neurological manifestations in 34 patients with hemophagocytic lymphohistiocytosis (HLH) in a single center. Clinical, radiological, and cerebrospinal fluid (CSF ) cytology data were analyzed according to treatment modalities. Twenty-five patients (73%) had evidence of central nervous system (CNS) disease at time of diagnosis, stressing the frequency of CNS involvement early in the time course of HLH. Four additional patients who did not have initial CNS disease, who did not die early from HLH complications, and who were not transplanted, also developed a specific CNS disease. Therefore, all surviving and nontransplanted patients had CNS involvement. Initially, CNS manifestations consisted of isolated lymphocytic meningitis in 20 patients and meningitis with clinical and radiological neurological symptoms in nine patients. For these nine patients, neurological symptoms consisted of seizures, coma, brain stem symptoms, or ataxia. The outcome of patients treated by systemic and intrathecal chemotherapy and/or immunosuppression exclusively (n = 16) was poor, as all died following occurrence of multiple relapses or CNS disease progression in most cases. Bone marrow transplantation (BMT) from either an HLA identical sibling (n = 6) or haplo identical parent (n = 3) was performed in nine patients, once first remission of CNS and systemic disease was achieved. Seven are long-term survivors including three who received an HLA partially identical marrow. All seven are off treatment with normal neurological function and cognitive development. In four other patients, BMT performed following CNS relapses was unsuccessful. Given the frequency and the poor outcome of CNS disease in HLH, BMT appears, therefore, to be the only available treatment procedure that is capable of preventing HLH CNS disease progression and that can result in cure when performed early enough after remission induction.

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Neurological disorders in autism: A systematic review and meta-analysis

Autism ◽

10.1177/1362361320951370 ◽

2020 ◽

pp. 136236132095137 ◽

Cited By ~ 1

Author(s):

Pei-Yin Pan ◽

Sven Bölte ◽

Preet Kaur ◽

Sadia Jamil ◽

Ulf Jonsson

Keyword(s):

Systematic Review ◽

Health Care ◽

Nervous System ◽

Cerebral Palsy ◽

General Population ◽

Neurological Disorders ◽

Migraine Headache ◽

Meta Analysis ◽

Full Range ◽

Neurological Complications

The etiological significance of neurological disorders in autism is debated, but it is clear that they complicate support provision and clinical management, and can have negative impact on outcomes. This systematic review and meta-analysis explored the full range of co-occurring neurological disorders in autism. We estimated the odds of having neurological complications compared to the general population and other neurodevelopmental conditions, as well as the overall prevalence of different neurological disorders. Seventy-nine articles were eligible for the systematic review, including 28 case-control studies, 43 prevalence studies, and 8 cohort studies. Findings were heterogeneous across studies. Overall, autistic individuals were significantly more likely than the general population to exhibit epilepsy, macrocephaly, hydrocephalus, cerebral palsy, migraine/headache, and congenital abnormalities of the nervous system, with prevalence estimates ranging from 1.1% (0%–3.3%; hydrocephalus) to 14.2% (11.3%–17.2%; epilepsy). Epilepsy was also more common in autism than in attention-deficit/hyperactivity disorder (odds ratio [95% confidence interval] = 4.06 [2.81–5.88]). Findings indicate that awareness of neurological disorders and neurological check-ups are indicated in autism to ensure adequate physical health care and support. Prospective studies of neurological disorders in children diagnosed with or at risk of autism might further enhance our understanding of causal pathways. Lay abstract Neurological disorders, such as epilepsy and cerebral palsy, have been reported to occur among individuals with autism beyond chance and may have an impact on daily living across the lifespan. Although there has been research investigating neurological disorders in autism, the findings are not always conclusive. Previous summaries of existing studies have not evaluated the full range of neurological disorders. This study aimed to comprehensively explore the neurological problems appearing in autism to provide updated information that is needed for better healthcare and support in this population. We looked at already published studies focusing on risk or frequency of neurological disorders in autism. Our results suggest that individuals with autism are more likely than the general population to have a range of neurological disorders, including epilepsy, macrocephaly, hydrocephalus, cerebral palsy, migraine/headache, and inborn abnormalities of the nervous system. In order to provide individualized healthcare and support of high quality to individuals diagnosed with autism, health care professionals and other support providers need to be attentive to neurological complications. To further improve our understanding about the link between autism and neurological disorders, future research should follow the neurological health of children who are diagnosed with or are at increased likelihood of autism.

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