key: cord-291588-tp89j1kk
authors: Dorche, Maryam Sharifian; Huot, Philippe; Osherov, Micheal; Wen, Dingke; Saveriano, Alexander; Giacomini, Paul; Antel, Jack P.; Mowla, Ashkan
title: Neurological complications of coronavirus infection; a comparative review and lessons learned during the COVID-19 pandemic
date: 2020-08-07
journal: J Neurol Sci
DOI: 10.1016/j.jns.2020.117085
sha: 
doc_id: 291588
cord_uid: tp89j1kk

INTRODUCTION: Coronavirus disease-19 (COVID-19) pandemic continues to grow all over the world. Several studies have been performed, focusing on understanding the acute respiratory syndrome and treatment strategies. However, there is growing evidence indicating neurological manifestations occur in patients with COVID-19. Similarly, the other coronaviruses (CoV) epidemics; severe acute respiratory syndrome (SARS-CoV-1) and Middle East respiratory syndrome (MERS-CoV) have been associated with neurological complications. METHODS: This systematic review serves to summarize available information regarding the potential effects of different types of CoV on the nervous system and describes the range of clinical neurological complications that have been reported thus far in COVID-19. RESULTS: Two hundred and twenty-five studies on CoV infections associated neurological manifestations in human were reviewed. Of those, 208 articles were pertinent to COVID-19. The most common neurological complaints in COVID-19 were anosmia, ageusia, and headache, but more serious complications, such as stroke, impairment of consciousness, seizures, and encephalopathy, have also been reported. CONCLUSION: There are several similarities between neurological complications after SARS-CoV-1, MERS-CoV and COVID-19, however, the scope of the epidemics and number of patients are very different. Reports on the neurological complications after and during COVID-19 are growing on a daily basis. Accordingly, comprehensive knowledge of these complications will help health care providers to be attentive to these complications and diagnose and treat them timely.

Coronavirus disease-19 pandemic continues to grow all over the world. Several studies have been performed, focusing on understanding the acute respiratory syndrome and treatment strategies. However, there is growing evidence indicating neurological manifestations occur in patients with . Similarly, the other coronaviruses (CoV) epidemics; severe acute respiratory syndrome (SARS-CoV-1) and Middle East respiratory syndrome (MERS-CoV) have been associated with neurological complications.

HCoV-OC43 and HCoV-229E.

CNS damages caused by HCoV was suggested in the 1980s. In 1980 Burks JS et al. (10) isolated CoV from the brains of two MS patients. Subsequently the. hypothesis concerning the relationship between CoV infection and demyelinating diseases in humans CNS was studied several times. (10, 11, 12) Arbour N et al showed that human CNS cells including oligodendrocytes, astrocytes, microglia, and neurons are susceptible to acute infection with HCoV-OC43 during in vitro cultures, and other than microglia, the rest have a potential of persistent infection. (13) In animal studies, direct invasion of the virus via nasal canal caused a rapid CNS infection. (14) . Cristallo A et al (11) reported presence of HCoV-OC43 RNA in the CSF of MS patients; However, Dessau RB et al. (12) did not find any evidence of chronic 229E or OC43 infection in brain tissue of MS patients. In 1992, Fazzini E et al showed higher levels of HCoV-OC43, and HCoV-229E antibodies in Cerebrospinal fluid (CSF) of Parkinson disease patients compared to controls. (9) Two cases of fatal encephalitis with HCoV-OC43 infection were reported in 2 immunosuppressed infants (9-month old infant on chemotherapy for leukemia and 11-month boy with severe combined immunodeficiency). (15, 16) Moreover, acute disseminated encephalomyelitis(ADEM) was reported with HCoV-OC43 infection in a 15-year-old boy. In this case, CSF was positive for the virus. (17) In 2015, acute flaccid paralysis was reported in a 3-year-old girl after infection with HCoV 229E and OC43 (18) In another study by Li Y et al. (19) from China, CoV was suggested as an important cause of acute encephalitis-like syndrome in children.

The outbreak of SARS-CoV-1 was in 2002-2003 and affected more than 8,000 people worldwide. (20) Clinical presentations in most of the patients were a simple common cold. However, in patients with an impaired immune system, it caused respiratory distress, pneumonia, and even death. (20) In some of these patients, neurological complications were reported. (Table 1 ) (21-28). Cerebrovascular pathologies and ischemic strokes were reported in 5 patients. Most of these patients had severe infection and several comorbidities, which might have made them more susceptible to stroke. (21) In these cases, hypo-perfusion as result of septic shock, utilization of intravenous immunoglobulin as a part of the treatment regimen, hypercoagulability state, cardiogenic shock, and vasculitis might represent the potential underlying mechanisms for the cerebrovascular events. (21) Encephalitis was reported in a 39-year-old patient. In his autopsy, SARS-CoV-1 RNA was isolated from the specimen and virions were visualized in neurons on electron microscopy. (24) Other studies on brain tissue specimens of autopsy donors detected SARS-CoV-1 in the cytoplasm of neurons in the cortex and hypothalamus. (29) Headache and dizziness have been reported as two of the most common initial presentations in many patients with COVID-19. These two are very common symptoms in many neurological pathologies such as meningitis, encephalitis and vasculitis. It was shown that they can also occur in temporal association with a systemic viral infection. (38, 39, 40) In COVID-19, headache has been reported in 2073 patients in 34 studies. (Table 3) The severity of headache was reported to be moderate to severe. Headaches were reported to have tension-type quality, (69) pain was reported to be bilateral with exacerbation by bending over, and mostly located in the temporo-parietal region or sometimes more anteriorly toward the forehead. (38) In most of these patients, headaches occurrence was associated with a past medical history of headaches. (69) Several potential underlying pathophysiological mechanisms were suggested, particularly for headaches in the forehead and periorbital regions (38); notably, it could be due to a direct invasion of SARS-CoV-2 to the trigeminal nerve endings in the nasal cavity. The other proposed underlying mechanism is trigemino-vascular activation due to involvement of the endothelial cells of the vessel walls with high expression of angiotensin-converting enzyme 2 (ACE2). A third proposed mechanism, the release of the pro-inflammatory mediators and cytokines during COVID-19 might stimulate the perivascular trigeminal nerve endings and cause headache. (38) We summarized the studies which reported Headache and dizziness in patients with COVID-19 in Table 3 .

Eleven studies reported dizziness as one of the presenting symptoms of COVID-19 in 173 patients. (Table  3 ) Kong Z et al. (72) reported a 53-year-old woman with dizziness as the initial symptom of COVID-19.

Acute Ischemic stroke(AIS) has been reported in approximately 1-3% of patients with 77, 84) ; this is similar with other CoV infections (SARS-CoV-1 and MERS-CoV). During the current pandemic, 370 patients with SARS-CoV-2 infection out of 37 studies (Table 3) were reported to suffer from AIS or transient ischemic attack (TIA). Most of these patients had several underlying co-morbidities which made them more susceptible to thromboembolic events. (21, 77).

However, there are reports on AIS occurring in young adults with SARS-Cov-2 infection and without any past medical history or cardiovascular risk factors. (80,85,95) ( Figure. 4 ). Systemic effects of SARS-Cov-2 might be the underlying mechanism in these cases. Coagulation abnormalities have been shown in critically ill COVID 19 patients. This was characterized by rise in procoagulant factors, including serum levels of fibrinogen (94%), platelet (62%), interleukin-6 (IL-6) and D-dimer (100%) which subsequently may contribute to elevated rate of thromboembolic events and higher rate of mortality and morbidity. (103) . SARS-CoV-2 may cause an inflammatory response in the body. Elevated levels of C-reactive protein (CRP), interleukin-7 (IL-7), IL-6 and other inflammatory markers makes the existing atherosclerotic plaque more susceptible to rupture (84). Cardiac manifestations and arrhythmic complications of COVID-19 can be another potential mechanism contributing to higher rate of ischemic events in these patients. (104) . The other proposed mechanism involves ACE2. It was shown that SARS-CoV-2 virus binds to ACE2 which is located in the lung, small intestinal and brain vessel endothelial cells. In critically ill patients, COVID-19 has been associated with coagulopathies such as DIC, thrombocytopenia, elevated D-dimer, and prolonged prothrombin time which can result in hemorrhage. (113) Another potential mechanism is the effect of SARS-CoV-2 on ACE2. As mentioned earlier, SARS-CoV-2 has been shown to use the ACE 2 receptor for cell entry. ACE2, the SARS-CoV-2 binding site, is a critical component of the counter-regulatory pathway of the RAS, which is one of the most important regulators of blood pressure. SARS-CoV-2-induced ACE2 downregulation may lead to vasoconstriction and dysfunction of cerebral autoregulation and subsequently blood pressure spikes which eventually can causes arterial wall rupture and hemorrhage. (106) . There are reports that suggested even neurosurgical interventions were accompanied with more hemorrhagic complications in patients with COVID-19. (113) Cerebral Venous Sinus Thrombosis was reported in 13 patients out of 9 studies. (Table 3) 

As of now, five patients with ADEM have been reported after CoV infection; one adolescent with HCoV-OC43 (17) and 4 adults after SARS-CoV-2. (120-123) relation between CoV infections and demyelinating diseases of CNS has been suggested in last decades. (12, 124) Despite the fact of ADEM usually occurring in children (17) , in the current pandemic all reported ADEM patients were older than 50-year-old. This finding might be due to higher prevalence of COVID-19 in adults. From the reported patients, two recovered with methylprednisolone and intravenous immunoglobulins (120,121) and two of them died (122,123), one was a 71-year-old-man with underlying comorbidities and ADEM was diagnosed in postmortem biopsy. (122) The other one was a 58-year-old man who was treated with dexamethasone and died as consequence of status epilepticus. (123) (Figure. 5)

Early insights about COVID-19 in MS patients suggest that the risk of infection and associated morbidity in this population is not significantly different from the non-COVID19 patients (130) Moreover, worsening outcome with regards to with disease-modifying therapies has not been reported. (131) Acute encephalomyelitis in COVID-19, were reported in 4 patients. (Table 3 

Decreased level of consciousness and Encephalopathy were reported in 7.5%(39) to 31%(98) of the patients with COVID-19 in 22 articles encompassing 454 patients. (Table 3 ) Altered consciousness is a general term with several underlying mechanisms. In COVID-19 patients, possible mechanisms include infections, parenchymal damages, electrolyte imbalance, hypoxic, toxic and metabolic encephalopathies and non-convulsive status epilepticus. (58,100,134, 135)

Leukoencephalopathy after COVID-19 was reported in 18 patients out of 3 studies. Radmanesh A et al. (145) reported diffuse white matter T2 hyperintensity plus restricted diffusion in 11 critically ill COVID-19 patients. Despite the fact that these findings are nonspecific and that their exact etiology is not certain; they attributed such findings to delayed post-hypoxic leukoencephalopathy. This pattern has been described in patients approximately 10-14 days after a hypoxic insult such as carbon monoxide poisoning, drug overdose, and cardiopulmonary arrests (145) and It is believed to relate to oligodendroglial cell death and subsequently demyelination. Other potential etiologies can be direct cerebral infection, sepsis-associated encephalopathy, post-infectious demyelination, and posterior reversible encephalopathy syndrome (PRES). (145) Acute Necrotizing Encephalopathy(ANE) which was reported in 8 patients (Table 3) with COVID-19 is a distinct entity defined as rapid onset of neurological symptoms often secondary to a viral infection such as herpes viruses and influenza. Despite the association with viral infection, ANE is usually not considered as an inflammatory encephalitis. The cytokine storm which has been described with SARS-CoV-2 and some other viral infections can cause ANE, particularly in critically ill patients. In the absence Posterior reversible encephalopathy syndrome (PRES) usually presents with acute impairment in level of consciousness, headache, visual disturbance and seizures. It is usually associated with cortical or subcortical vasogenic edema, involving predominantly the parietal and occipital regions bilaterally. (163) This condition is commonly associated with fluctuation in blood pressure, renal failure, autoimmune conditions, infections and sepsis, preeclampsia or eclampsia and certain type of immunosuppressivecytotoxic drugs. (163) PRES was reported in ten COVID-19 patients out of 8 studies. (Table 3 ) Definitive etiology is not fully understood but there are various proposed underlying mechanisms. In COVID-19, endothelial dysfunction related to SARS-CoV-2 in combination with hemodynamic instability and immunological activation with release of cytokines may increase the vascular permeability in the brain tissue. Furthermore, disruption of BBB in these cases may cause vasogenic edema and PRES. (162) (163) Kishfy L et al. (165) suggested that COVID-19 patients may be at higher risk of consequences of uncontrolled hypertension such as hypertensive encephalopathy and PRES due to endothelial dysfunction. For this reason, tight blood pressure control was suggested, particularly in ventilated COVID-19 patients.

Seizure has been reported as a neurological manifestation in patients infected with SARS-CoV-1 (23), MERS-CoV (32) and SARS-CoV-2. In COVID-19, 48 patients out of 20 studies were reported to have seizures. (Table 3) . CNS viral infections and subsequent activation of neuro-inflammatory pathways are known to lower the threshold for seizures and potentially facilitate epileptogenesis in certain individuals. (174) As an example, in a COVID-19 patient with prior structural brain damage, focal seizures originating from the lesion site was reported. (175) Moreover, the accumulation of inflammatory markers associated with SARS-CoV-2 infection, may cause a local cortical irritation that precipitates seizures (177) . In addition, viral encephalitis and direct invasion of the virus to the CNS may cause seizure in the affected patients. (177, 178) In critically ill COVID-19 patients, metabolic and J o u r n a l P r e -p r o o f electrolyte imbalances, ongoing hypoxia and inflammatory/infectious processes may also contribute to seizure or abnormal EEG background. (134) In a recent study on electroencephalography (EEG) findings of COVID-19 patients by Galanopoulou AS et al. (180) , sporadic epileptiform activity, predominantly in the form of frontal sharp waves, were detected in 40.9% of patients with altered mental status. (180) . "Generalized background slowing" particularly in patients with decreased level of consciousness was reported in several investigations. (178, 180, 181) It was also shown that previous diagnosis of epilepsy can be a potential risk factor for COVID-19-associated seizure. (181)

There are few reports about movement disorders in COVID-19. Rábano-Suárez P et al. (182) reported 3 patients with generalized myoclonus with both positive and negative jerks, with predominantly involved the facial, sternocleidomastoid, trapezius, and upper extremities muscles. In those patients, myoclonus occurred spontaneously and were extremely sensitive to multisensory stimuli (auditive and tactile) or voluntary movements. After Immunotherapy, all 3 patients improved, at least partially. (182) Another study reported (183) a previously healthy 58-year-old man with COVID-19 who developed generalized myoclonus, fluctuating level of consciousness, opsoclonus, right-side dominant hypokineticrigid syndrome, and frank hypomimia. The patient also had brief conjugated, multidirectional, and chaotic saccadic ocular movements. DaT-SPECT confirmed bilateral decreased presynaptic dopamine uptake asymmetrically involving bilateral putamen. Parkinsonian symptoms in this patient improved spontaneously without specific treatment. Association between viral infection and Parkinson's disease was suggested decades ago, namely since the Spanish Flu Pandemic (5) . As mentioned earlier, Fazzini E et al revealed elevated levels of HCoV-OC43 and HCoV-229E antibodies in the CSF of patients with Parkinson's disease (9) Given scanty available about such association, no definite conclusion can be drawn.

Hanafi R, et al. (185) reported a 65-year-old man with COVID-19 who had extensive diffuse subcortical ischemic lesions in the brain resembling cerebral vasculitis. (Figure 8 ) He also developed a characteristic lower extremity skin rash. SARS-CoV-2 infects the host through its CoV spike glycoprotein, which binds to the ACE2 receptor. ACE2 receptor has higher expression in neurons and cerebral vessel endothelial cells which can cause high level of CNS invasion. (185, 186) Histologic evidence of COVID-19-induced vasculitis has been reported in several other organs including lung, kidney, liver and skin. (186) Similarly, virus-related endothelial injury and endotheliitis might cause CNS vasculitis.

Anosmia and Ageusia, the prevalence of anosmia and ageusia ranges widely in different studies from 5% in a study from China (39) to about 88% in an Italian study (56). Smell impairment was also reported in SARS-CoV-1 and influenza infections. (209) , reported a 25-year-old female with anosmia and subtle hyper-intensity signal in the olfactory bulbs and also cortical hyper-intensity in the right gyrus rectus. In follow/up MRI after 28 days, the olfactory bulbs were thinner and slightly less hyper-intense and the signal alteration in the cortex had completely disappeared. (Figure 9) The olfactory system is also considered as a potential route of virus entry. Various studies suggested that CoV may have CNS direct invasion via olfactory bulb. (146, 159) Visual Impairments after COVID-19 was reported in 12 patients out of 3 studies. Selvaraj V et al. (204) reported a middle aged woman with COVID-19 who presented with sudden onset painless right eye monocular visual blurriness. Brain and orbit MRIs were unremarkable and eye examinations were normal. posterior ischemic optic neuropathy was considered as the cause. Thromboembolic events, systematic inflammation associated with COVID-19 and invasion of CoV to the CNS through the hematogenous route or direct invasion through the cribriform plate or conjunctiva were considered the potential underlying mechanisms. (204)

Impaired Eye movement associated with COVID-19 was described in 12 patients out of 4 studies. (Table  4 ) Pascual-Goñi E et al. (194) , reported a 60-year-old woman with right abducens nerve palsy. In brain MRI examination, FLAIR hyper-intensity of the pontine tegmentum and right sixth cranial nerve nucleus was noted.

Trigeminal neuropathy was reported in 9 patients out of 2 studies. (Table 4 ) de Freitas Ferreira ACA et al (216) reported a 39-year-old man with trigeminal neuropathy associated with SARS-Cov-2 and herpes zoster co-infection.

GBS can occur post gastrointestinal or respiratory illness. The suggested mechanism is molecular mimicry in which the pathogen likely share epitopes similar to the components of the peripheral nerves. The antibodies produced by the host immune system to fight the virus, cross-react and bind to the peripheral nerves causing neuronal dysfunction. 

Skeletal muscle injury and myopathy have been reported in COVID-19 patients. (Table 5 ) In the severe COVID-19 patients, critical illness myopathy has been reported. Major proposed risk factors for this type of myopathy are severe respiratory distress, systemic inflammatory response and sepsis. (250, 251) Moreover direct invasion of the muscle by the virus is the other potential mechanism for myopathy. Similar to SARS-CoV-1, SARS-CoV-2 have the ability to penetrate the cells that express ACE2 receptors. As ACE2 is expressed in the muscle cells, the possibility of invasion of the muscles by the virus entering the cells via the ACE2 receptors should also be considered. In addition, hyper-inflammation and cytokine storms in the advanced phase of COVID-19 could cause immune-mediated muscle damage. (250) Considering the growing number of patients with COVID-19, myopathy should be considered as a major cause of long-term physical disability (251)

There are several similarities between neurological manifestations of different CoV infections. encephalitis was reported in HCoV-OC43, SARS-CoV-1, MERS-CoV and SARS-CoV-2 infections. (15, 16, 24, 33, 60, 98, 100, 150, 151, 151, 152, 153, 154, 155, 156, 157, 158) ADEM was reported after HCoV-OC43 and SARS-CoV-2 infection. (17, 120, 121, 122, 123) Headache, ischemic stroke, encephalitis and encephalopathy, seizure and neuropathy were reported in all the pandemics associated with CoV (SARS-CoV-1, MERS-CoV and SARS-CoV-2). ICH was reported in MERS-CoV and COVID-19 and myopathy and anosmia were reported in SARS-CoV-1 and COVID-19. (Figure 10 )

In this review, we tried to gather and summarize the results of all the studies reporting neurological disorders observed in patients with CoV infections. However, in some of the reported patients, the neurological manifestations might not be associated with the CoV infections and just coincidentally occurred due to the patient's underlying commodities. Moreover, in patients with severe CoV infections, the associated sepsis and organs failure my lead to different neurological presentations which can be seen in any of critical conditions. In addition, in several studies, particularly in the case of COVID-19, sufficient investigations have not been performed and hard to believe that the neurological manifestation was related to CoV infection. Finally, yet importantly, the neurological symptoms in some of these patients might be medications side effects given CoV infected patients have been treated with different classes of medications, which have side effects, not necessarily reported in the studies.

There are similarities between the neurological complications associated with SARS-CoV-1, MERS-CoV and COVID-19. However, the scope of the pandemics and number of patients involved in each are different. Thus far, SARS-CoV-2 has infected millions of people worldwide. Reports on the neurological complications after and during COVID-19 are growing on a daily basis. Better understanding of the potential associated neurological complications will help health care providers to be more attentive to these complications and a more timely diagnosis and management.

Authors have no relevant financial disclosure to report. 

Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms

500-year evolution of the term epidemic

Influenza: historical aspects of epidemics and pandemics

Discussion on Influenza

Viral parkinsonism

History and recent advances in coronavirus discovery

China Novel Coronavirus Investigating and Research Team. A novel coronavirus from patients with pneumonia in China

Two coronaviruses isolated from central nervous system tissue of two multiple sclerosis patients

Human coronavirus polyadenylated RNA sequences in cerebrospinal fluid from multiple sclerosis patients

Coronaviruses in brain tissue from patients with multiple sclerosis

Acute and persistent infection of human neural cell lines by human coronavirus OC43

Axonal transport enables neuron-to-neuron propagation of human coronavirus OC43

Fatal encephalitis associated with coronavirus OC43 in an immunocompromised child

Human coronavirus OC43 associated with fatal encephalitis

Detection of Coronavirus in the central nervous system of a child with acute disseminated encephalomyelitis

A rare cause of acute flaccid paralysis: Human coronaviruses

Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Clinical features of patients infected with 2019 novel coronavirus in Wuhan

Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study

Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China

Clinical Characteristics of Fatal and Recovered Cases of Coronavirus Disease 2019 (COVID-19) in Wuhan, China: A Retrospective Study

Clinical characteristics of 2019 novel coronavirus infection in China. medRxiv

Epidemiologic and clinical characteristics of novel coronavirus infections involving 13 patients outside Wuhan, China

Longitudinal Change of SARS-Cov2 Antibodies in Patients with COVID-19

Clinical Features of Patients with Coronavirus Disease 2019 (COVID-19) from a Designated Hospital in Beijing

Headache as the Presenting Symptom in 2 Patients with COVID-19 and a History of Migraine: 2 Case Reports

Neurologic Manifestations in Hospitalized Patients With COVID-19: The ALBACOVID Registry

Anosmia in COVID-19 patients

Subjective neurological symptoms frequently occur in patients with SARS-CoV2 infection

Neurologic Involvement in COVID-19: Cause or Coincidence? A Neuroimaging Perspective

Characteristics of COVID-19 infection in Beijing

Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms

Clinical and epidemiologic profile of the initial COVID-19 patients at a tertiary care centre in India

Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: Retrospective case series

Prothrombotic state induced by COVID-19 infection as trigger for stroke in young patients: A dangerous association. eNeurologicalSci

New onset neurologic events in people with COVID-19 infection in three regions in China

Ischemic Stroke Associated With Novel Coronavirus 2019: A Report of Three Cases

Unusual simultaneous cerebral infarcts in multiple arterial territories in a COVID-19 patient

Neurovascular Complications in COVID-19 Infection: Case Series

COVID-19 and Acute Ischemic Stroke -A Case Series From Dubai, UAE

Incidence and consequences of systemic arterial thrombotic events in COVID-19 patients

Macrothrombosis and stroke in patients with mild Covid-19 infection

Neurologic Features in Severe SARS-CoV-2 Infection

Acute ischemic stroke complicating common carotid artery thrombosis during a severe COVID-19 infection

Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study

Acute Cerebrovascular Disease Following COVID-19: A Single Center

COVID-19 related neuroimaging findings: A signal of thromboembolic complications and a strong prognostic marker of poor patient outcome

Imaging in Neurological Disease of Hospitalized COVID-19 Patients: An Italian Multicenter Retrospective Observational Study

Concomitant Brain Arterial and Venous Thrombosis in a COVID-19 Patient

The procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome

Cardiac and arrhythmic complications in patients with COVID-19

COVID-19-related stroke

COVID 19, and intracerebral hemorrhage: causative or coincidental. New Microbes New Infect

Letter to editor: Severe brain haemorrhage and concomitant COVID-19 Infection: A neurovascular complication of COVID-19

Intracerebral Hemorrhage and SARS-CoV-2: Association or Causation

Intracerebral haemorrhage and COVID-19: Clinical characteristics from a case series

A case of COVID-19 pneumonia with cerebral hemorrhage

COVID-19 Presenting With Thalamic Hemorrhage Unmasking Moyamoya Angiopathy

Catastrophic Intracranial Hemorrhage in Two Critically Ill Patients with COVID-19. Neurocrit Care

Acute hemorrhage after intra-cerebral biopsy in COVID-19 patients: a report of 3 cases

Atypical Deep Cerebral Vein Thrombosis with Hemorrhagic Venous Infarction in a Patient Positive for COVID-19

COVID-19-associated acute necrotizing myelitis

Transient acute-onset tetraparesis in a COVID-19 patient

Acute transverse myelitis after COVID-19 pneumonia

Bar-Or A. COVID-19 and MS disease-modifying therapies

Clinical Characteristics and Outcomes in Patients with Coronavirus Disease 2019 and Multiple Sclerosis

A case of possible atypical demyelinating event of the central nervous system following COVID-19

Concomitant neurological symptoms observed in a patient diagnosed with coronavirus disease 2019

Seizures associated with coronavirus infections

New onset acute symptomatic seizure and risk factors in coronavirus disease 2019: A retrospective multicenter study

Acute Encephalopathy With Elevated CSF Inflammatory Markers as the Initial Presentation of COVID-19. Version 2

Delirium as a presenting feature in COVID-19: Neuroinvasive infection or autoimmune encephalopathy? Brain Behav Immun

Encephalopathy: Detection of Antibodies Against SARS-CoV-2 in CSF

Neurological Complications of Coronavirus Disease (COVID-19): Encephalopathy, MRI Brain and Cerebrospinal Fluid Findings: Case 2. Cureus

Risk factors for incident delirium among older people in acute hospital medical units: a systematic review and meta-analysis

HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression

COVID-19-Associated Leukoencephalopathy

COVID-19 -associated Diffuse Leukoencephalopathy and Microhemorrhages

Acute necrotizing encephalopathy with SARS-CoV-2 RNA confirmed in cerebrospinal fluid

COVID-19-associated delayed posthypoxic necrotizing leukoencephalopathy

COVID-19-associated acute hemorrhagic necrotizing encephalopathy: CT and MRI features

COVID-19-related acute necrotizing encephalopathy with brain stem involvement in a patient with aplastic anemia

A first case of meningitis/encephalitis associated with SARS-Coronavirus-2

Plasmapheresis treatment in COVID-19-related autoimmune meningoencephalitis: Case series

Steroid-responsive encephalitis in Covid-19 disease

COVID-19-associated meningoencephalitis complicated with intracranial hemorrhage: a case report

Encephalitis as a clinical manifestation of COVID-19

COVID-19-Associated Encephalitis Mimicking Glial Tumor. World Neurosurg

Evolution and resolution of brain involvement associated with SARS-CoV2 infection: A close Clinical -Paraclinical follow up study of a case

Central Nervous System Involvement by Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2)

COVID-19-associated Mild encephalitis/encephalopathy With a Reversible Splenial Lesion

Hemorrhagic Posterior Reversible Encephalopathy Syndrome as a Manifestation of COVID-19 Infection

Transient cortical blindness in COVID-19 pneumonia; a PRES-like syndrome: Case report

Reversible Encephalopathy Syndrome (PRES) in a COVID-19 Patient

Verapamil as treatment for refractory status epilepticus secondary to PRES syndrome on a SARS-Cov-2 infected patient

Posterior reversible encephalopathy syndrome (PRES) as a neurological association in severe Covid-19

De Novo Status Epilepticus in patients with COVID-19

Non-lesional status epilepticus in a patient with coronavirus disease 2019

Seizure with CSF lymphocytosis as a presenting feature of COVID-19 in an otherwise healthy young man

A case of COVID-19 infection presenting with a seizure following severe brain edema

Non-epileptic seizures in autonomic dysfunction as the initial symptom of COVID-19

Orbitofrontal involvement in a neuroCOVID-19 patient

Focal EEG changes indicating critical illness associated cerebral microbleeds in a Covid-19 patient. Version 2

Frequent convulsive seizures in an adult patient with COVID-19: a case report

First case of focal epilepsy associated with SARS-coronavirus-2

Focal Status Epilepticus as Unique Clinical Feature of COVID-19: A Case Report

Encephalopathy and seizure activity in a COVID-19 well controlled HIV patient. IDCases

Acute Symptomatic Seizures in Critically Ill Patients with COVID-19: Is There an Association? Neurocrit Care

COVID-19)-Associated Encephalopathies and Cerebrovascular Disease: The New Orleans Experience. World Neurosurg

SARS-CoV-2 can induce brain and spine demyelinating lesions

EEG Findings in Acutely Ill Patients Investigated for SARS-CoV-2/COVID-19: A Small Case Series Preliminary Report. Version 2. Epilepsia Open

EEG Findings in Coronavirus Disease

Generalized myoclonus in COVID-19

Acute Hypokinetic-Rigid Syndrome Following SARS-CoV-2 Infection

COVID-19 Neurologic Complication with CNS Vasculitis-Like Pattern

Pathological findings of COVID-19 associated with acute respiratory distress syndrome

COVID-19-White matter and globus pallidum lesions: Demyelination or small-vessel vasculitis? Neurol Neuroimmunol Neuroinflamm

Leukoencephalopathy Associated with Severe COVID-19 Infection: Sequela of Hypoxemia?

Pearls & Oy-sters: Bilateral globus pallidus lesions in a patient with COVID-19

Early postmortem brain MRI findings in COVID-19 non-survivors

Guillain-Barré syndrome associated with leptomeningeal enhancement following SARS-CoV-2 infection

Brain MRI Findings in Patients in the Intensive Care Unit with COVID-19 Infection

Multifocal Laminar Cortical Brain Lesions: A Consistent MRI Finding in neuro-COVID-19 Patients

Encephalomyelitis associated with Covid-19 infection: case report. r J Neurosurg

Brain Imaging Use and Findings in COVID-19: A Single Academic Center Experience in the Epicenter of Disease in the United States

Smell dysfunction: a biomarker for COVID-19. Int Forum Allergy Rhinol

Isolated sudden onset anosmia in COVID-19 infection. A novel syndrome?

Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study

Acute-onset smell and taste disorders in the context of COVID-19: a pilot multicentre polymerase chain reaction based case-control study

Acute anosmia from COVID-19 infection

An Online Observational Study of Patients With Olfactory and Gustory Alterations Secondary to SARS-CoV-2 Infection. Front Public Health

Acute Vision Loss in a Patient with COVID-19

Olfactory and Gustatory Dysfunction in a COVID-19 Patient with Ankylosing Spondylitis Treated with Etanercept: Case Report

Quantitative evaluation of olfactory dysfunction in hospitalized patients with Coronavirus [2] (COVID-19)

Bilateral transient olfactory bulbs edema during COVID-19-related anosmia

Anosmia and olfactory tract neuropathy in a case of COVID-19

Magnetic Resonance Imaging Alteration of the Brain in a Patient With Coronavirus Disease 2019 (COVID-19) and Anosmia

Olfactory Bulb Magnetic Resonance Imaging in SARS-CoV-2-Induced Anosmia: The First Report

Prevalence and Duration of Acute Loss of Smell or Taste in COVID-19 Patients

Anosmia and ageusia: common findings in COVID-19 patients

younger age in ambulatory settings -a multicenter cross-sectional study

COVID-19 presenting with ophthalmoparesis from cranial nerve palsy

COVID-19 and herpes zoster co-infection presenting with trigeminal neuropathy

Pearls and Oy-sters: Facial nerve palsy as a neurological manifestation of Covid-19 infection

Guillain Barre syndrome associated with COVID-19 infection: A case report

Early Guillain-Barré syndrome in coronavirus disease 2019 (COVID-19): a case report from an Italian COVID-hospital

COVID-19 may induce Guillain-Barré syndrome

Guillain-Barré syndrome related to COVID-19 infection

Guillain-Barré syndrome associated with SARS-CoV-2 infection: causality or coincidence?

Covid-19 and Guillain-Barré syndrome: More than a coincidence! Rev Neurol (Paris)

Guillain-Barre syndrome during SARS-CoV-2 pandemic: a case report and review of recent literature

Guillain-Barré Syndrome Associated with SARS-CoV-2

SARS-CoV-2 Associated Guillain-Barre Syndrome with Dysautonomia. Muscle Nerve

Guillain-Barré Syndrome associated with SARS-CoV-2 infection

Miller Fisher Syndrome and polyneuritis cranialis in COVID-19

Guillain-Barré Syndrome as a Complication of SARS-CoV-2 Infection

Facial diplegia, a possible atypical variant of Guillain-Barré Syndrome as a rare neurological complication of SARS-CoV-2

Guillain-Barré syndrome in a patient infected with SARS-CoV-2, a case report

Acute inflammatory demyelinating polyneuritis in association with an asymptomatic infection by SARS-CoV-2

COVID-19-Associated Bifacial Weakness with Paresthesia Subtype of Guillain-Barré Syndrome

Guillain-Barré syndrome following COVID-19: a newly emerging post-infectious complication

Guillain-Barré syndrome after SARS-CoV-2 infection

Guillain-Barré Syndrome in a Patient With Antibodies Against SARS-COV-2

Miller Fisher Syndrome Diagnosis and Treatment in a Patient With SARS-CoV-2

Correction to: New clinical manifestation of COVID-19 related Guillain-Barrè syndrome highly responsive to intravenous immunoglobulins: two Italian cases

Miller-Fisher syndrome after SARS-CoV-2 infection

Guillain-Barré Syndrome in a Patient With Minimal Symptoms of COVID-19 Infection

SARS-CoV-2 and Guillain-Barré syndrome: AIDP variant with favorable outcome

Novel Coronavirus (COVID

Associated Guillain-Barré Syndrome: Case Report

Guillain-Barré syndrome in the COVID-19 era: just an occasional cluster?

Guillain-Barré syndrome following COVID-19: new infection, old complication?

Guillain-Barré Syndrome as a Neurological Complication of Novel COVID-19 Infection: A Case Report and Review of the Literature

COVID-19-Associated Miller Fisher Syndrome: MRI Findings

Acute polyradiculoneuritis with locked-in syndrome in a patient with Covid-19

COVID 19 infection presenting as motor peripheral neuropathy

Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of Coronavirus Disease 2019: A Review

Acute myopathic quadriplegia in COVID-19 patients in the intensive care unit

Critical illness myopathy as a consequence of Covid-19 infection

COVID-19 associated myositis with severe proximal and bulbar weakness

Seizure 20 Articles

reported a 70 Y/O patient with non-epileptic seizures

174) reported 73 Y/O F with focal epilepsy

175)reported a case of focal status epilepticus from left fronto-centro-temporal area(MRI showed extensive gliosis and atrophy at that site due to previous herpes encephalitis

 (41) , (42) , (43) , (44) , (45) , (46) , (47) , (48) , (49),. (50), (51) , (52), (53), (54), (55), 56), (57), (58), (59) , (60) , (61) , (62) , (63) , (64) , (65) , (66) , (67) , (68), (69),.(70), (178) 2073 NR in all articles. (195) , (197)