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1.
J Neurol Res ; 10(4): 113-121, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-1227221

ABSTRACT

Coronavirus (CoV) is a virus infectious disease with a considerable spectrum of clinical presentations. Symptoms ranged from asymptomatic infection to severe pneumonia that may lead to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and several clinical complications. Neurologic symptoms related to CoV have been described recently in the literature. The relationship between SARS-CoV-2 and the central nervous system (CNS) is still not clear. This review aimed to reveal the current knowledge regarding CNS manifestation in SARS-CoV-2. A systematic literature review was carried out to identify the particularities of coronavirus disease 2019 (COVID-19) in patients with CNS involvement, using the PubMed database between January 1, 2020 and April 30, 2020. Conference papers, reviews, published letters, editorials, studies in pregnant women and children, and studies only reporting on a specific factor were excluded. An initial search included as many as 83 articles. Out of the 83 screened articles, 32 were selected for full-text review. Sixteen studies were excluded because they did not analyze nervous system involvement in SARS-CoV-2 infection. Thus, 16 papers were included in this review. There were three retrospective studies and 13 case reports/series of cases. Data from the current literature reveal that patients who suffer from a severe illness have more CNS involvement, neurological symptoms (i.e., dizziness, headache) and an association with strokes. The severe patients had higher D-dimer and C-reactive protein levels than non-severe patients and presented multiple organ involvement, such as serious liver, kidney and muscle damage.

2.
Hosp Pract (1995) ; 49(3): 157-163, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1069189

ABSTRACT

There is increasing evidence of the ability of the novel coronavirus to invade the central nervous system (CNS). But how does a respiratory virus invade the highly protected CNS? Here, we reviewed available literature and case reports to determine CNS involvement in COVID-19, and to identify potential regions of the brain that may be affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its possible route of entry into the brain to identify its pathogenicity. Based on the symptoms, the parietal lobe and the cerebellum are the likely targets of SARS-CoV-2; however, further work is needed to elucidate this. The presence of ACE2, used by SARS-CoV-2 for cell entry, in the brain as well as detection of the virus in the cerebrospinal fluid, further assert that SARS-COV-2 targets the brain, and therefore, medical practitioners should take that into account when dealing with patients suffering from COVID-19.


Subject(s)
Blood-Brain Barrier/virology , COVID-19/virology , Central Nervous System/virology , SARS-CoV-2/pathogenicity , Blood-Brain Barrier/pathology , Brain/virology , COVID-19/pathology , Central Nervous System/pathology , Cerebrospinal Fluid/virology , Humans
3.
Int J Infect Dis ; 102: 155-162, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1060140

ABSTRACT

OBJECTIVES: To analyze the cerebrospinal fluid (CSF) of patients with SARS-CoV-2 infection and neurological manifestations to provide evidence for the understanding of mechanisms associated with central nervous system (CNS) involvement in COVID-19. METHODS: Patients (n = 58) were grouped according to their main neurological presentation: headache (n = 14); encephalopathy (n = 24); inflammatory neurological diseases, including meningoencephalitis (n = 4), acute myelitis (n = 3), meningitis (n = 2), acute disseminated encephalomyelitis (ADEM) (n = 2), encephalitis (n = 2), and neuromyelitis optica (n = 1); and Guillain-Barré syndrome (n = 6). Data regarding age, sex, cerebrovascular disease, and intracranial pressure were evaluated in combination with CSF profiles defined by cell counts, total protein and glucose levels, concentration of total Tau and neurofilament light chain (NfL) proteins, oligoclonal band patterns, and detection of SARS-CoV-2 RNA. RESULTS: CSF of patients with inflammatory neurological diseases was characterized by pleocytosis and elevated total protein and NfL levels. Patients with encephalopathy were mostly older men (mean age of 61.0 ± 17.6 years) with evidence of cerebrovascular disease. SARS-CoV-2 RNA in CSF was detected in 2 of 58 cases: a patient with refractory headache, and another patient who developed ADEM four days after onset of COVID-19 symptoms. Three patients presented intrathecal IgG synthesis, and four had identical oligoclonal bands in CSF and serum, indicating systemic inflammation. CONCLUSION: Patients with neurological manifestations associated with COVID-19 had diverse CSF profiles, even within the same clinical condition. Our findings indicate a possible contribution of viral replication on triggering CNS infiltration by immune cells and the subsequent inflammation promoting neuronal injury.


Subject(s)
COVID-19/complications , Nervous System Diseases/cerebrospinal fluid , SARS-CoV-2 , Adult , Aged , COVID-19/cerebrospinal fluid , Female , Humans , Inflammation/diagnosis , Male , Middle Aged , Nervous System Diseases/etiology
4.
Stroke ; 51(12): 3719-3722, 2020 12.
Article in English | MEDLINE | ID: covidwho-1050419

ABSTRACT

BACKGROUND AND PURPOSE: Case series indicating cerebrovascular disorders in coronavirus disease 2019 (COVID-19) have been published. Comprehensive workups, including clinical characteristics, laboratory, electroencephalography, neuroimaging, and cerebrospinal fluid findings, are needed to understand the mechanisms. METHODS: We evaluated 32 consecutive critically ill patients with COVID-19 treated at a tertiary care center from March 9 to April 3, 2020, for concomitant severe central nervous system involvement. Patients identified underwent computed tomography, magnetic resonance imaging, electroencephalography, cerebrospinal fluid analysis, and autopsy in case of death. RESULTS: Of 32 critically ill patients with COVID-19, 8 (25%) had severe central nervous system involvement. Two presented with lacunar ischemic stroke in the early phase and 6 with prolonged impaired consciousness after termination of analgosedation. In all but one with delayed wake-up, neuroimaging or autopsy showed multiple cerebral microbleeds, in 3 with additional subarachnoid hemorrhage and in 2 with additional small ischemic lesions. In 3 patients, intracranial vessel wall sequence magnetic resonance imaging was performed for the first time to our knowledge. All showed contrast enhancement of vessel walls in large cerebral arteries, suggesting vascular wall pathologies with an inflammatory component. Reverse transcription-polymerase chain reactions for SARS-CoV-2 in cerebrospinal fluid were all negative. No intrathecal SARS-CoV-2-specific IgG synthesis was detectable. CONCLUSIONS: Different mechanisms of cerebrovascular disorders might be involved in COVID-19. Acute ischemic stroke might occur early. In a later phase, microinfarctions and vessel wall contrast enhancement occur, indicating small and large cerebral vessels involvement. Central nervous system disorders associated with COVID-19 may lead to long-term disabilities. Mechanisms should be urgently investigated to develop neuroprotective strategies.


Subject(s)
COVID-19/diagnostic imaging , Cerebral Arteries/diagnostic imaging , Cerebral Hemorrhage/diagnostic imaging , Cerebrovascular Disorders/diagnostic imaging , Ischemic Stroke/diagnostic imaging , Aged , Antibodies, Viral/cerebrospinal fluid , Brain Ischemia/diagnostic imaging , Brain Ischemia/etiology , COVID-19/cerebrospinal fluid , COVID-19/complications , COVID-19/physiopathology , COVID-19 Nucleic Acid Testing , COVID-19 Serological Testing , Cerebral Hemorrhage/etiology , Cerebrospinal Fluid/immunology , Cerebrospinal Fluid/virology , Cerebrovascular Disorders/cerebrospinal fluid , Cerebrovascular Disorders/etiology , Cerebrovascular Disorders/physiopathology , Consciousness Disorders/etiology , Consciousness Disorders/physiopathology , Contrast Media , Critical Illness , Electroencephalography , Female , Humans , Ischemic Stroke/etiology , Magnetic Resonance Imaging , Male , Middle Aged , SARS-CoV-2 , Severity of Illness Index , Switzerland , Tertiary Care Centers , Tomography, X-Ray Computed
5.
Acta Neurol Belg ; 121(2): 331-339, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1037229

ABSTRACT

Coronavirus disease (COVID-19) was first identified in late December 2019. The disease began in Wuhan, Hubei province in China and since then it has spread quickly to many countries all over the world. COVID-19 is caused by a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus was majorly seen to overwhelm the respiratory system with mild to severe acute respiratory syndrome considered pathognomic for the disease. However, with time a plethora of symptoms was observed in the patients infected with COVID-19 including strong evidence for neurological symptoms. Evidence suggests that the virus has both central and peripheral nervous system manifestations. Patients, particularly those who suffer from a severe illness, have a central nervous system (CNS) involvement and neurological manifestations. There is precise and targeted documentation of neurological symptoms with details of clinical, neurological, and electrophysiological findings. This review article thus gives an insight into the neuro-invasive potential of COVID-19 and discusses the possible pathogenesis.


Subject(s)
COVID-19/complications , Nervous System Diseases/virology , Humans , SARS-CoV-2
6.
J Neuroimaging ; 31(2): 228-243, 2021 03.
Article in English | MEDLINE | ID: covidwho-1015550

ABSTRACT

BACKGROUND AND PURPOSE: The ongoing Coronavirus Disease 2019 (COVID-19) pandemic is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is occasionally associated with manifold diseases of the central nervous system (CNS). We sought to present the neuroimaging features of such CNS involvement. In addition, we sought to identify typical neuroimaging patterns that could indicate possible COVID-19-associated neurological manifestations. METHODS: In this systematic literature review, typical neuroimaging features of cerebrovascular diseases and inflammatory processes associated with COVID-19 were analyzed. Reports presenting individual patient data were included in further quantitative analysis with descriptive statistics. RESULTS: We identified 115 studies reporting a total of 954 COVID-19 patients with associated neurological manifestations and neuroimaging alterations. A total of 95 (82.6%) of the identified studies were single case reports or case series, whereas 660 (69.2%) of the reported cases included individual information and were thus included in descriptive statistical analysis. Ischemia with neuroimaging patterns of large vessel occlusion event was revealed in 59.9% of ischemic stroke patients, whereas 69.2% of patients with intracerebral hemorrhage exhibited bleeding in a location that was not associated with hypertension. Callosal and/or juxtacortical location was identified in 58.7% of cerebral microbleed positive images. Features of hemorrhagic necrotizing encephalitis were detected in 28.8% of patients with meningo-/encephalitis. CONCLUSIONS: Manifold CNS involvement is increasingly reported in COVID-19 patients. Typical and atypical neuroimaging features have been observed in some disease entities, so that familiarity with these imaging patterns appears reasonable and may assist clinicians in the differential diagnosis of COVID-19 CNS manifestations.


Subject(s)
Brain/diagnostic imaging , COVID-19/diagnostic imaging , Humans , Magnetic Resonance Imaging , Neuroimaging , Pandemics , Tomography, X-Ray Computed
7.
Indian J Crit Care Med ; 24(10): 975-980, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-931212

ABSTRACT

With increasing knowledge of the coronavirus disease-2019 (COVID-19), we now understand that COVID-19 presents with various extrapulmonary manifestations with multi-organ involvement. Involvement of the central nervous system (CNS) occurs probably via transsynaptic spread or transfer across the blood-brain barrier. Hypoxia, immune-mediated injury, and vascular damage are the potential mechanisms for the CNS manifestations. Headache, dizziness, chemosensory disturbances, such as loss of smell, taste, encephalopathy, stroke, etc., are among the commonly encountered neurological presentations. Headache is identified as one of the red flag symptoms for COVID-19. Sudden onset of loss of smell and/or taste in the absence of nasal congestion can help in COVID-19 case identification and testing prioritization. Both hemorrhagic and ischemic brain injury is common in patients developing stroke. Besides these, COVID-19-associated CNS involvement demands more careful attention toward patients with existing neurological disorders especially that are managed with immunosuppressant agents. In all, neurological involvement in COVID-19 is not uncommon and may precede, occur concomitantly or after the respiratory involvement. It may also be the sole presentation in some of the patients necessitating high vigilance for COVID-19. In this review, we briefly discussed the pathogenesis of CNS involvement and some important neurological manifestations in COVID-19. How to cite this article: Zirpe KG, Dixit S, Kulkarni AP, Sapra H, Kakkar G, Gupta R, et al. Pathophysiological Mechanisms and Neurological Manifestations in COVID-19. Indian J Crit Care Med 2020;24(10):975-980.

8.
Neuropathol Appl Neurobiol ; 47(1): 3-16, 2021 02.
Article in English | MEDLINE | ID: covidwho-884895

ABSTRACT

There is increasing evidence that patients with Coronavirus disease 19 (COVID-19) present with neurological and psychiatric symptoms. Anosmia, hypogeusia, headache, nausea and altered consciousness are commonly described, although there are emerging clinical reports of more serious and specific conditions such as acute cerebrovascular accident, encephalitis and demyelinating disease. Whether these presentations are directly due to viral invasion of the central nervous system (CNS) or caused by indirect mechanisms has yet to be established. Neuropathological examination of brain tissue at autopsy will be essential to establish the neuro-invasive potential of the SARS-CoV-2 virus but, to date, there have been few detailed studies. The pathological changes in the brain probably represent a combination of direct cytopathic effects mediated by SARS-CoV-2 replication or indirect effects due to respiratory failure, injurious cytokine reaction, reduced immune response and cerebrovascular accidents induced by viral infection. Further large-scale molecular and cellular investigations are warranted to clarify the neuropathological correlates of the neurological and psychiatric features seen clinically in COVID-19. In this review, we summarize the current reports of neuropathological examination in COVID-19 patients, in addition to our own experience, and discuss their contribution to the understanding of CNS involvement in this disease.


Subject(s)
COVID-19/complications , COVID-19/pathology , Nervous System Diseases/pathology , Nervous System Diseases/virology , Female , Humans , Male , SARS-CoV-2
9.
Neuroradiol J ; 33(5): 368-373, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-646969

ABSTRACT

Central nervous system involvement in severe acute respiratory syndrome caused by coronavirus disease 2019 (COVID-19) has increasingly been recognised in the literature, and possible mechanisms of neuroinvasion, neurotropism and neurovirulence have been described. Neurological signs have been described in 84% of COVID-19 intensive care unit patients, and haemostatic abnormalities in such patients may play an important role, with a broad spectrum of neuroimaging findings. This report describes the magnetic resonance imaging neurovascular findings in an acutely ill patient with COVID-19, including perfusion abnormalities depicted in the arterial spin labelling technique.


Subject(s)
Brain/diagnostic imaging , Cerebrovascular Circulation , Coronavirus Infections/diagnostic imaging , Pneumonia, Viral/diagnostic imaging , Subarachnoid Hemorrhage/diagnostic imaging , Aged , Betacoronavirus , Brain/blood supply , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/physiopathology , Corpus Callosum , Frontal Lobe , Humans , Intracranial Hemorrhages , Magnetic Resonance Imaging , Male , Pandemics , Parietal Lobe , Perfusion Imaging , Pneumonia, Viral/complications , Pneumonia, Viral/physiopathology , SARS-CoV-2 , Spin Labels , Subarachnoid Hemorrhage/complications , Thalamus
10.
Rev Neurosci ; 31(4): 453-456, 2020 05 26.
Article in English | MEDLINE | ID: covidwho-401430

ABSTRACT

Coronaviruses disease (COVID-19) has caused major outbreaks. A novel variant, SARS-CoV-2, is responsible for COVID-19 pandemic. Clinical presentations and pathological mechanisms of COVID-19 are broad. The respiratory aspect of the disease has been extensively researched. Emerging studies point out the possibility of the central nervous system (CNS) involvement by COVID-19. Here, we discuss the current evidence for CNS involvement in COVID-19 and highlight that the high pathogenicity of SARS-CoV-2 might be due to its neuroinvasive potential.


Subject(s)
Central Nervous System Viral Diseases/physiopathology , Coronavirus Infections/physiopathology , Pneumonia, Viral/physiopathology , Severe Acute Respiratory Syndrome/physiopathology , Angiotensin-Converting Enzyme 2 , Betacoronavirus/metabolism , Betacoronavirus/physiology , Blood-Brain Barrier , Brain Stem , COVID-19 , Dipeptidyl Peptidase 4/metabolism , Ethmoid Bone , Humans , Middle East Respiratory Syndrome Coronavirus , Olfactory Mucosa , Pandemics , Peptidyl-Dipeptidase A/metabolism , SARS Virus , SARS-CoV-2 , Thalamus , Viral Tropism , Virus Internalization
11.
J Neurol Sci ; 413: 116832, 2020 06 15.
Article in English | MEDLINE | ID: covidwho-47914

ABSTRACT

OBJECTIVE: In this systematic review, we will discuss the evidence on the occurrence of central nervous system (CNS) involvement and neurological manifestations in patients with COVID-19. METHODS: MEDLINE (accessed from PubMed) and Scopus from December 01, 2019 to March 26, 2020 were systematically searched for related published articles. In both electronic databases, the following search strategy was implemented and these key words (in the title/abstract) were used: "COVID 19" OR "coronavirus" AND "brain" OR "CNS" OR "neurologic". RESULTS: Through the search strategy, we could identify two articles about neurological involvement by COVID-19. One of these publications was a narrative review and the other one was a viewpoint. However, the authors scanned the reference lists of the included studies and could identify multiple references. One study, specifically investigated the neurological manifestations of COVID-19 and could document CNS manifestations in 25% of the patients. Most of the studies investigated the manifestations of COVID-19 in general. CONCLUSION: While neurological manifestations of COVID-19 have not been studied appropriately, it is highly likely that some of these patients, particularly those who suffer from a severe illness, have CNS involvement and neurological manifestations. Precise and targeted documentation of neurological symptoms, detailed clinical, neurological, and electrophysiological investigations of the patients, attempts to isolate SARS-CoV-2 from cerebrospinal fluid, and autopsies of the COVID-19 victims may clarify the role played by this virus in causing neurological manifestations.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/virology , Nervous System Diseases/virology , Pneumonia, Viral/virology , COVID-19 , Humans , Pandemics , SARS-CoV-2
12.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(4): 359-366, 2020 Apr 10.
Article in Chinese | MEDLINE | ID: covidwho-18354

ABSTRACT

Since December 2019, a series of highly infectious cases of unexplained pneumonia have been discovered in Wuhan, Hubei Province, which have been confirmed as '2019 corona virus disease' caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 virus can invade many human systems including the lungs. Patients with central nervous system involvement may show a series of neurological symptoms, which is easy to be misdiagnosed and neglected, thereby increasing the risk of SARS-CoV-2 transmission. Hereditary ataxia is a large group of neurodegenerative diseases with great clinical and genetic heterogeneity and high mortality and disability. In view of the seriousness of the COVID-19 epidemic, a series of prevention and control measures adopted by the government have restricted the follow-up, diagnosis and treatment of patients by the hospitals, which has a great impact on their mental and physical health. In order to standardize the management of patients during the prevention and control of COVID-19 epidemic, the Specialized Committee of Neurogenetics of the Neurophysician Branch of Chinese Medical Doctor Association has formulated this consensus, with an aim to help patients to overcome the difficulties and pass the epidemic prevention period safely.


Subject(s)
Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Spinocerebellar Degenerations , Betacoronavirus , COVID-19 , China/epidemiology , Consensus , Coronavirus Infections/complications , Epidemics , Health Status , Humans , Mental Health , Nervous System Diseases/virology , Pandemics , Pneumonia, Viral/complications , SARS-CoV-2 , Spinocerebellar Degenerations/complications , Spinocerebellar Degenerations/diagnosis , Spinocerebellar Degenerations/prevention & control , Spinocerebellar Degenerations/therapy
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