An unresponsive COVID-19 patient.

Neurological manifestations and complications are increasingly reported in coronavirus disease-19 (COVID-19) patients. Although pulmonary manifestations are more common, patients with severe disease may present with neurological symptoms such as in our case. We describe a case report of a 50-year-old male without previous known comorbidity who was found unresponsive due to COVID-19-related neurological complications. During this pandemic, an emergency radiologist should be well acquainted with various neurological manifestations of COVID-19. In this article, we will discuss the pathogenesis, imaging findings, and differentials of this disease.

Myeloencephalitis as the only presentation of Omicron SARS-CoV-2 infection.

SARS-CoV-2 is now a major global health issue and manifests mainly as a respiratory disorder. Several other complications involving hypercoagulability, cardiovascular system and central nervous system have been described in the literature. Among these atypical presentations, encephalopathy associated with SARS-CoV-2 is a rare entity with heterogenous clinical and radiological findings. The direct presence of SARS-CoV-2 in cerebrospinal fluid (CSF) was rarely found in encephalopathy patients with acute SARS-Cov-2 infection.Here, we report a case of myeloencephalitis with positive real-time PCR for SARS-CoV-2 in CSF in a young woman presenting exclusively with neurological symptoms. Other differential diagnosis were extensively pursued by a comprehensive aetiological workup. To our knowledge, this is the first case report in the Omicron era. In the context of recent global explosion of SARS-Cov-2 infections, clinicians should consider this pathogen among other possible neurotropic agents and be familiar with its radiological and clinical presentations.

Delayed encephalopathy after COVID-19: A case series of six patients.

RATIONALE: Acute encephalopathy is a severe neurological complication of coronavirus disease 2019 (COVID-19). Most cases of acute encephalopathy associated with COVID-19 occur within several weeks of COVID-19 onset. We describe a case series of 6 patients who developed delayed encephalopathy (DE) after COVID-19. PATIENT CONCERNS AND DIAGNOSES: We evaluated patients who recovered from COVID-19 and showed acute disturbance of consciousness or focal neurological deficits without recurrence of pneumonitis. Six patients, 2 females and 4 males, with ages ranging from 65 to 83 years were included. Durations of hospitalization due to COVID-19 were between 25 and 44 days. The severity of COVID-19 was moderate in 5 and severe in 1 patient. Patients were rehospitalized for acute disturbance of consciousness concomitant with postural tremor and, abnormal behavior, hemiplegia, aphasia, or apraxia between 34 and 67 days after the onset of COVID-19. Chest computed tomography showed no exacerbation of pneumonitis. Brain magnetic resonance imaging showed no specific findings except in 1 patient with an acute lacunar infarction. Electroencephalogram demonstrated diffuse slowing in all patients. Repeat electroencephalogram after recovery from encephalopathy demonstrated normal in all patients. One of the 6 patients had cerebrospinal fluid (CSF) pleocytosis. CSF protein levels were elevated in all patients, ranging from 51 to 115 mg/dL. CSF interleukin-6 levels ranged from 2.9 to 10.9 pg/mL. The immunoglobulin index was 0.39 to 0.44. Qlim(alb) < QAlb indicating dysfunction of the blood-brain barrier was observed in all patients. Severe acute respiratory syndrome coronavirus 2 reverse transcription polymerase chain reaction of CSF was negative in all patients. Neuronal autoantibodies were absent in serum and CSF. INTERVENTIONS AND OUTCOMES: Immunotherapy including steroid pulses was administered to 3 patients; however, symptoms of encephalopathy resolved within several days in all patients, regardless of treatment with immunotherapy, and their consciousness levels were recovered fully. Notably, postural tremor remained for 2 weeks to 7 months. LESSONS: In our patients, DE after COVID-19 was characterized by symptoms of acute encephalopathy accompanied with tremor in the absence of worsening pneumonitis after the fourth week of COVID-19 onset. Our findings indicate blood-brain barrier dysfunction may contribute to the pathogenesis of DE after COVID-19.

Mechanisms of coronavirus infectious disease 2019-related neurologic diseases.

PURPOSE OF REVIEW: As of January 8, 2022, a global pandemic caused by infection with severe acute respiratory syndrome coronavirus (SARS-CoV)-2, a new RNA virus, has resulted in 304,896,785 cases in over 222 countries and regions, with over 5,500,683 deaths (www.worldometers.info/coronavirus/). Reports of neurological and psychiatric symptoms in the context of coronavirus infectious disease 2019 (COVID-19) range from headache, anosmia, and dysgeusia, to depression, fatigue, psychosis, seizures, delirium, suicide, meningitis, encephalitis, inflammatory demyelination, infarction, and acute hemorrhagic necrotizing encephalopathy. Moreover, 30-50% of COVID-19 survivors develop long-lasting neurologic symptoms, including a dysexecutive syndrome, with inattention and disorientation, and/or poor movement coordination. Detection of SARS-CoV-2 RNA within the central nervous system (CNS) of patients is rare, and mechanisms of neurological damage and ongoing neurologic diseases in COVID-19 patients are unknown. However, studies demonstrating viral glycoprotein effects on coagulation and cerebral vasculature, and hypoxia- and cytokine-mediated coagulopathy and CNS immunopathology suggest both virus-specific and neuroimmune responses may be involved. This review explores potential mechanistic insights that could contribute to COVID-19-related neurologic disease. RECENT FINDINGS: While the development of neurologic diseases during acute COVID-19 is rarely associated with evidence of viral neuroinvasion, new evidence suggests SARS-CoV-2 Spike (S) protein exhibits direct inflammatory and pro-coagulation effects. This, in conjunction with immune dysregulation resulting in cytokine release syndrome (CRS) may result in acute cerebrovascular or neuroinflammatory diseases. Additionally, CRS-mediated loss of blood-brain barrier integrity in specific brain regions may contribute to the expression of proinflammatory mediators by neural cells that may impact brain function long after resolution of acute infection. Importantly, host co-morbid diseases that affect vascular, pulmonary, or CNS function may contribute to the type of neurologic disease triggered by SARS-COV-2 infection. SUMMARY: Distinct effects of SARS-CoV-2 S protein and CNS compartment- and region-specific responses to CRS may underlie acute and chronic neuroinflammatory diseases associated with COVID-19.

Acute cerebellitis following SARS-CoV-2 infection: A case report and review of the literature.

Novel coronavirus disease (COVID-19) first described in Wuhan, China in December 2019, has rapidly spread across the world and become a global public health emergency. Literature on the neurological manifestations of COVID-19 is limited. We report a 24-year-old male, who presented with vertigo, dysarthria, and bradyphrenia 3 weeks after being diagnosed with COVID-19 on nasopharyngeal reverse transcription polymerase chain reaction. The patient was diagnosed with acute cerebellitis based on magnetic resonance imaging features and showed improvement posttreatment with intravenous methylprednisone for 5 days. The scope of this article is to highlight the importance of early identification of neurological symptoms and timely management as the outcomes may be catastrophic.

Neuropathology and Inflammatory Cell Characterization in 10 Autoptic COVID-19 Brains.

COVID-19 presents with a wide range of clinical neurological manifestations. It has been recognized that SARS-CoV-2 infection affects both the central and peripheral nervous system, leading to smell and taste disturbances; acute ischemic and hemorrhagic cerebrovascular disease; encephalopathies and seizures; and causes most surviving patients to have long lasting neurological symptoms. Despite this, typical neuropathological features associated with the infection have still not been identified. Studies of post-mortem examinations of the cerebral cortex are obtained with difficulty due to laboratory safety concerns. In addition, they represent cases with different neurological symptoms, age or comorbidities, thus a larger number of brain autoptic data from multiple institutions would be crucial. Histopathological findings described here are aimed to increase the current knowledge on neuropathology of COVID-19 patients. We report post-mortem neuropathological findings of ten COVID-19 patients. A wide range of neuropathological lesions were seen. The cerebral cortex of all patients showed vascular changes, hyperemia of the meninges and perivascular inflammation in the cerebral parenchyma with hypoxic neuronal injury. Perivascular lymphocytic inflammation of predominantly CD8-positive T cells mixed with CD68-positive macrophages, targeting the disrupted vascular wall in the cerebral cortex, cerebellum and pons were seen. Our findings support recent reports highlighting a role of microvascular injury in COVID-19 neurological manifestations.

Presentation of COVID-19 infection with bizarre behavior and encephalopathy: a case report.

BACKGROUND: Current studies show that patients with severe coronavirus disease 2019 (COVID-19) have neurological symptoms manifesting as acute cerebrovascular diseases, impaired consciousness, and skeletal muscle symptoms. Bizarre behavior is an unusual and unique presenting symptom of COVID-19 infection in our patient. CASE PRESENTATION: We report a case of COVID-19 infection in a middle aged Iranian man without underlying disease who presented with bizarre behavior. Results of brain imaging were normal, but COVID-19 pneumonia was detected on chest computed tomography scan. Given the respiratory problem and positive polymerase chain reaction (PCR) test for COVID-19, treatment with hydroxychloroquine was administered, and after 2 days all of the symptoms resolved. CONCLUSIONS: Encephalopathy and encephalitis may be a possible presentation of COVID-19. Clinicians and health care providers should consider the presence of COVID-19 with bizarre behavior during this COVID-19 pandemic.

Encephalopathy in patients with COVID-19: A review.

Encephalopathy and encephalitis are major and devastating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus-associated central nervous system complications. Hypoxic/metabolic changes produced by intense inflammatory response against the virus triggers cytokine storm and subsequently acute respiratory distress syndrome and multiple organ failure. Hypoxic/metabolic changes result in encephalopathy. The presence of comorbidities predisposes to hypoxic/metabolic changes responsible for encephalopathy. Altered consciousness, ranging from mild confusion, delirium, to deep coma, is hallmark clinical features. Cortical and subcortical T2/FLAIR signal changes are common neuroimaging abnormalities. In a few isolated case reports of SARS-CoV-2 encephalitis, the virus has been demonstrated in cerebrospinal fluid. The presence of anosmia and ageusia can help in differentiation from other encephalopathies. We analyzed published reports on coronavirus disease 2019-associated encephalopathy. Encephalopathy is common in older patients, the majority are more than 50 years of age. The patients having encephalopathy/encephalitis are either severely or critically ill. Many patients were already on mechanical ventilation. Lung abnormalities are noted in almost all of the patients, presenting with encephalopathy. Encephalopathy is always preceded by commoner clinical features, like, fever, cough, dyspnoea, and headache. In majority, patients are already in the intensive care unit, when encephalopathy develops.

The olfactory route is a potential way for SARS-CoV-2 to invade the central nervous system of rhesus monkeys.

Neurological manifestations are frequently reported in the COVID-19 patients. Neuromechanism of SARS-CoV-2 remains to be elucidated. In this study, we explored the mechanisms of SARS-CoV-2 neurotropism via our established non-human primate model of COVID-19. In rhesus monkey, SARS-CoV-2 invades the CNS primarily via the olfactory bulb. Thereafter, viruses rapidly spread to functional areas of the central nervous system, such as hippocampus, thalamus, and medulla oblongata. The infection of SARS-CoV-2 induces the inflammation possibly by targeting neurons, microglia, and astrocytes in the CNS. Consistently, SARS-CoV-2 infects neuro-derived SK-N-SH, glial-derived U251, and brain microvascular endothelial cells in vitro. To our knowledge, this is the first experimental evidence of SARS-CoV-2 neuroinvasion in the NHP model, which provides important insights into the CNS-related pathogenesis of SARS-CoV-2.

Neuroimaging Findings of Hospitalized Covid-19 Patients: A Canadian Retrospective Observational Study.

PURPOSE: Coronavirus disease (COVID-19) has been associated with neurologic sequelae and neuroimaging abnormalities in several case series previously. In this study, the neuroimaging findings and clinical course of adult patients admitted with COVID-19 to a tertiary care hospital network in Canada were characterized. METHODS: This is a retrospective observational study conducted at a tertiary hospital network in Ontario, Canada. All adult patients with PCR-confirmed COVID-19 admitted from February 1, 2020 to July 22, 2020 who received neuroimaging related to their COVID-19 admission were included. CT and MR images were reviewed and categorized by fellowship-trained neuroradiologists. Demographic and clinical data were collected and correlated with imaging findings. RESULTS: We identified 422 patients admitted with COVID-19 during the study period. 103 (24.4%) met the inclusion criteria and were included: 30 ICU patients (29.1%) and 73 non-ICU patients (70.9%). A total of 198 neuroimaging studies were performed: 177 CTs and 21 MRIs. 17 out of 103 imaged patients (16.8%) had acute abnormalities on neuroimaging: 10 had macrohemorrhages (58.8%), 9 had acute ischemia (52.9%), 4 had SWI abnormalities (23.5%), and 1 had asymmetric sulcal effacement suggesting possible focal encephalitis (5.8%). ICU patients were more likely to have positive neuroimaging findings, more specifically acute ischemia and macrohemorrhages (P < 0.05). Macrohemorrhages were associated with increased mortality (P < 0.05). CONCLUSION: Macrohemorrhages, acute ischemia and SWI abnormalities were the main neuroimaging abnormalities in our cohort of hospitalized COVID-19 patients. Acute ischemia and hemorrhage were associated with worse clinical status.

Central nervous system vasculopathy associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): a novel case report from Iran.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents respiratory symptoms as the most common clinical manifestations. Similar to some other viral infections, it can cause severe neurological damages. Here, we describe a 40-year-old man case who initially was admitted to a major hospital with presenting 7 days with weak flu-like symptoms (cough) and fever then presented neurology signs for 3 days. Physical examination and brain magnetic resonance imaging (MRI) showed cerebral vasculopathy. Molecular testing was performed on nasopharyngeal swab by real-time reverse transcription polymerase chain reaction (RT-PCR) which was positive for SARS-CoV-2. The patient received supportive cares and was treated with routine antiplatelet therapy. He was improved and discharged 10 days after admission with no symptoms. Our findings report a 40-year-old man with flu-like symptoms that indicate cerebral vasculopathy that was discharged with no symptoms. Therefore, physicians should be monitor patients with worsening or progressive central nervous system results. The pathobiology of this virus is still incompletely known; therefore, extensive studies are needed to reveal the effect of COVID-19 on the nervous system.

Encephalopathy and COVID-19: a case report.

Case numbers reported in literature with neurological manifestations potentially linked to COVID-19 is constantly increasing. Most often it is sudden anosmia, headache, encephalopathy or stroke. Pathophysiology of this neurological involvement is still poorly understood. While viral genome is very rarely detected in cerebrospinal fluid, inflammatory involvement is often very significant. We report a case of SARS-CoV-2 encephalopathy without respiratory distress or cytokine storm.

COVID-19 encephalopathy: Clinical and neurobiological features.

Severe acute respiratory coronavirus 2 (SARS-CoV-2) has been associated with neurological complications, including acute encephalopathy. To better understand the neuropathogenesis of this acute encephalopathy, we describe a series of patients with coronavirus disease 2019 (COVID-19) encephalopathy, highlighting its phenomenology and its neurobiological features. On May 10, 2020, 707 patients infected by SARS-CoV-2 were hospitalized at the Geneva University Hospitals; 31 (4.4%) consecutive patients with an acute encephalopathy (64.6 ± 12.1 years; 6.5% female) were included in this series, after exclusion of comorbid neurological conditions, such as stroke or meningitis. The severity of the COVID-19 encephalopathy was divided into severe and mild based on the Richmond Agitation Sedation Scale (RASS): severe cases (n = 14, 45.2%) were defined on a RASS < -3 at worst presentation. The severe form of this so-called COVID-19 encephalopathy presented more often a headache. The severity of the pneumonia was not associated with the severity of the COVID-19 encephalopathy: 28 of 31 (90%) patients did develop an acute respiratory distress syndrome, without any difference between groups (p = .665). Magnetic resonance imaging abnormalities were found in 92.0% (23 of 25 patients) with an intracranial vessel gadolinium enhancement in 85.0% (17 of 20 patients), while an increased cerebrospinal fluid/serum quotient of albumin suggestive of blood-brain barrier disruption was reported in 85.7% (6 of 7 patients). Reverse transcription-polymerase chain reaction for SARS-CoV-2 was negative for all patients in the cerebrospinal fluid. Although different pathophysiological mechanisms may contribute to this acute encephalopathy, our findings suggest the hypothesis of disturbed brain homeostasis and vascular dysfunction consistent with a SARS-CoV-2-induced endotheliitis.

New-Onset Seizures in Three COVID-19 Patients: A Case Series.

SUMMARY: Neurological manifestations of coronavirus disease 2019 most commonly present in severe cases and range from mild complications, such as headache and dizziness, to severe complications, such as encephalopathy and acute cerebrovascular disease. Seizures, however, are an underreported neurological manifestation of this disease. We present three critically ill coronavirus disease 2019 patients with EEG monitoring who developed new-onset seizures and encephalopathy up to three-and-a-half weeks after symptom onset. There are several speculated etiologies for the development of new-onset seizures; however, the pathogenic mechanism remains unknown. Testing of coronavirus disease 2019 in the cerebrospinal fluid in addition to extensive research on neurological manifestations is warranted.

Hyponatremia and Encephalopathy in a 55-Year-old Woman with Syndrome of Inappropriate Antidiuretic Hormone Secretion as an Isolated Presentation of SARS-CoV-2 Infection.

BACKGROUND During the coronavirus disease 2019 (COVID-19) pandemic of 2020, varied presentations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported. The present report is of a case of hyponatremia and encephalopathy due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) as the main presentation of SARS-CoV-2 infection in a 55-year-old woman. CASE REPORT A 55-year-old woman with type II diabetes mellitus presented with confusion and slurring of speech, with a temperature of 38.5°C, heart rate of 120 bpm, blood pressure of 159/81 mmHg, and oxygen saturation of 98% on room air. She did not have edema on examination. Laboratory testing showed a low sodium level of 116 mEq/L (reference range, 135-145 mEq/L) with urine osmolarity of 364 mOsm/kg, urinary sodium of 69 mEq/L, urinary potassium of 15.6 mEq/L, and serum osmolarity of 251 mOsm/kg. The patient had normal serum thyroid-stimulating hormone and cortisol levels. A chest X-ray should no pulmonary infiltrates nor did a lumbar puncture reveal signs of infection. A real-time SARS-CoV-2 polymerase chain reaction assay was positive for COVID-19. Brain imaging with computed tomography was negative for acute infarct, intracranial hemorrhage, and mass effect. Based on findings from laboratory testing and physical examination, a diagnosis of SIADH was made. The patient was treated with 3% hypertonic saline, followed by salt tablets and fluid restriction, with improvement in her clinical symptoms and serum sodium level. CONCLUSIONS The present report is of a rare but previously reported association with SARS-CoV-2 infection. Encephalopathy and hyponatremia associated with SIADH without pneumonia or other symptoms of infection should be an indication for testing for SARS-CoV-2 infection.