Peripheral neurological complications during COVID-19: A single center experience.

BACKGROUND AND AIMS: We highlight the peripheral neurologic complications of coronavirus disease 2019 (COVID-19) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an ongoing global health emergency. METHODS: We evaluated twenty-five patients admitted to the COVID-19 Recovery Unit (CRU) at New York-Presbyterian Weill Cornell University Medical Center after intensive care hospitalization with confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), whom neurology was consulted for weakness and/or paresthesias. All patients were clinically evaluated by a neuromuscular neurologist who performed electrodiagnostic (EDX) studies when indicated. Magnetic resonance imaging (MRI) of the affected regions, along with nerve and muscle biopsies were obtained in select patients to better elucidate the underlying diagnosis. RESULTS: We found fourteen out of twenty-five patients with prolonged hospitalization for COVID-19 infection to have peripheral neurological complications, identified as plexopathies, peripheral neuropathies and entrapment neuropathies. The other eleven patients were not found to have peripheral neurologic causes for their symptoms. Patients with peripheral neurological complications often exhibited more than one type of concurrently. Specifically, there were four cases of plexopathies, nine cases of entrapment neuropathies, and six cases of peripheral neuropathies, which included cranial neuropathy, sciatic neuropathy, and multiple mononeuropathies. CONCLUSIONS: We explore the possibility that the idiopathic peripheral neurologic complications could be manifestations of the COVID-19 disease spectrum, possibly resulting from micro-thrombotic induced nerve ischemia.

Neurological Manifestations of COVID-19 and the Importance of Magnetic Resonance Imaging.

A letter to the editor to discuss several uses of brain magnetic resonance imaging (MRI) in the investigation of neurological manifestations of covid-19. Described several situations in which the MRI is needed. Brain MRI is an important diagnostic method in the covid-19 scenario, to investigate possible neurological complications of the disease.

[COVID-19: neurological manifestations-update : What we know so far]. / COVID-19: neurologische Manifestationen ­ Update : Was wir bisher wissen.

Beyond pulmonary presentation, COVID-19 infection can manifest with a variety of both acute and chronic neurologic and neuropsychiatric (concomitant) symptoms and diseases. Nonspecific symptoms such as headache, fatigue, olfactory and gustatory disturbance have been reported more frequently, and severe disease such as encephalopathy, encephalitis, and cerebrovascular events have been reported relatively rarely. The heterogeneity of neurologic and neuropsychiatric presentations is large, as well as the range of recorded prevalences. Older patients, pre-existing neurologic and non neurologic comorbidities and severe COVID-19 disease were associated with increased risk of severe neurologic complications and higher in-hospital mortality. Probable neurotropic pathomechanisms of SARS-CoV­2 have been discussed, but a multifactorial genesis of neurologic/neuropsychiatric symptoms and disease beyond these is likely.

A Review of Robotic Interventional Neuroradiology.

Robotic interventional neuroradiology is an emerging field with the potential to enhance patient safety, reduce occupational hazards, and expand systems of care. Endovascular robots allow the operator to precisely control guidewires and catheters from a lead-shielded cockpit located several feet (or potentially hundreds of miles) from the patient. This has opened up the possibility of expanding telestroke networks to patients without access to life-saving procedures such as stroke thrombectomy and cerebral aneurysm occlusion by highly-experienced physicians. The prototype machines, first developed in the early 2000s, have evolved into machines capable of a broad range of techniques, while incorporating newly automated maneuvers and safety algorithms. In recent years, preliminary clinical research has been published demonstrating the safety and feasibility of the technology in cerebral angiography and intracranial intervention. The next step is to conduct larger, multisite, prospective studies to assess generalizability and, ultimately, improve patient outcomes in neurovascular disease.

Neurological Presentations of COVID-19: Characteristic Features in a Case Series of Hospitalized Patients from Abu Dhabi, UAE.

BACKGROUND: COVID-19 patients can present with neurological manifestations in the form of headache, dizziness, hyposmia, myalgia, peripheral neuropathy, acute cerebrovascular disease, and encephalopathy. Neurological involvement could be due to virus-induced brain hypoxia, brain infection, or immune reaction. We aim to describe the neurological presentation of COVID-19 patients and study their neuroimaging findings and disease outcome. METHOD: The study is a single-centre, retrospective, observational study in Sheikh Shakhbout Medical City (SSMC), Abu Dhabi, UAE. Patients diagnosed with COVID-19 between March and May 2020 who presented with neuropathological features with or without respiratory manifestations of COVID-19 were enrolled. Electronic records were studied for age, sex, duration of hospitalization, detailed neurological presentation, history or documented concomitant fever and respiratory features of COVID-19, inflammatory markers, neuroimaging, progress, and disease outcome. RESULTS: Thirty-three patients of 10 nationalities presented with neurological manifestations. Mean (range) age was 51.4 (21-86) years. Twenty-four had comorbidities, and 18 had no prior or concomitant respiratory symptoms. Ten patients presented with encephalopathy and exhibited altered behavior/sensorium: 7 presented with myositis, 8 with stroke, and 4 with seizures, and 4 had peripheral and cranial nerve involvement. The mean (average) duration of hospital stay was 11.4 days (1-38) with the longest observed in stroke patients. Fifteen patients (45%) died and 3 (9%) had residual weakness. Serum ferritin, CRP, and procalcitonin were higher in the severe disease group and correlated with risk of death. Twelve of 22 brain images showed abnormalities including haemorrhage, infarcts, small vessel ischemia, and oedema. Risk of death was higher in older age but did not differ based on the underlying neuropathology. CONCLUSION: COVID-19 patients who present with neurological involvement have a higher risk of mortality which is aggravated by older age and higher inflammatory markers. The type of neurological pathology does not seem to influence the risk of mortality.

Acute and chronic neurological disorders in COVID-19: potential mechanisms of disease.

Coronavirus disease 2019 (COVID-19) is a global pandemic caused by SARS-CoV-2 infection and is associated with both acute and chronic disorders affecting the nervous system. Acute neurological disorders affecting patients with COVID-19 range widely from anosmia, stroke, encephalopathy/encephalitis, and seizures to Guillain-Barré syndrome. Chronic neurological sequelae are less well defined although exercise intolerance, dysautonomia, pain, as well as neurocognitive and psychiatric dysfunctions are commonly reported. Molecular analyses of CSF and neuropathological studies highlight both vascular and immunologic perturbations. Low levels of viral RNA have been detected in the brains of few acutely ill individuals. Potential pathogenic mechanisms in the acute phase include coagulopathies with associated cerebral hypoxic-ischaemic injury, blood-brain barrier abnormalities with endotheliopathy and possibly viral neuroinvasion accompanied by neuro-immune responses. Established diagnostic tools are limited by a lack of clearly defined COVID-19 specific neurological syndromes. Future interventions will require delineation of specific neurological syndromes, diagnostic algorithm development and uncovering the underlying disease mechanisms that will guide effective therapies.

Demand for Essential Nonambulatory Neurosurgical Care Decreased While Acuity of Care Increased During the Coronavirus Disease 2019 (COVID-19) Surge.

BACKGROUND: In times of health resource reallocation, capacities must remain able to meet a continued demand for essential, nonambulatory neurosurgical acute care. This study sought to characterize the demand for and provision of neurosurgical acute care during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: This single-center cross-sectional observational analysis compared nonambulatory neurosurgical consult encounters during the peri-surge period (March 9 to May 31, 2020) with those during an analogous period in 2019. Outcomes included consult volume, distribution of problem types, disease severity, and rate of acute operative intervention. RESULTS: A total of 1494 neurosurgical consults were analyzed. Amidst the pandemic surge, 583 consults were seen, which was 6.4 standard deviations below the mean among analogous 2016-2019 periods (mean 873; standard deviation 45, P = 0.001). Between 2019 and 2020, the proportion of degenerative spine consults decreased in favor of spinal trauma (25.6% vs. 34% and 51.9% vs. 41.4%, P = 0.088). Among aneurysmal subarachnoid hemorrhage cases, poor-grade (Hunt and Hess grades 4-5) presentations were more common (30% vs. 14.8%, P = 0.086). A greater proportion of pandemic era consults resulted in acute operative management, with an unchanged absolute frequency of acutely operative consults (123/583 [21.1%] vs. 120/911 [13.2%], P < 0.001). CONCLUSIONS: Neurosurgical consult volume during the pandemic surge hit a 5-year institutional low. Amidst vast reallocation of health care resources, demand for high-acuity nonambulatory neurosurgical care continued and proportionally increased for greater-acuity pathologies. In our continued current pandemic as well as any future situations of mass health resource reallocation, neurosurgical acute care capacities must be preserved.

Coexistence of neurological diseases with Covid-19 pneumonia during the pandemic period.

Although clinical findings are related to respiration in the Covid-19 pandemic, the number of patients with neurological symptoms and signs is increasing. The purpose of this study was to assess the prevalence of Covid-19 pneumonia using thoracic CT in patients who presented to the emergency room with neurological complaints during the pandemic. We retrospectively examined the files of 1093 patients who admitted to the emergency room and had a Neurology consultation. The research involved patients who had a neurological diagnosis and had typical findings of COVID-19 pneumonia on thorax computed tomography (CT). The thoracic CT scans of 68 (6.2%) of 1093 patients with neurological disorders at the time of admission revealed results consistent with Covid-19 pneumonia. The "real-time reverse transcription polymerase chain reaction" (RT-PCR) was positive in 42 of the 68 patients (62%), and the patients were diagnosed with Covid-19. Ground glass opacity was the most common finding in thoracic CT in patients diagnosed with Covid-19 pneumonia, with a rate of 92.9% (n = 39). Ischemic stroke (n = 26, 59.5%), cerebral haemorrhage (n = 11, 28.6%), epilepsy (n = 3, 7.1%), transient ischaemic attack (TIA; n = 1, 2.4%), and acute inflammatory demyelinating polyneuropathy (n = 1, 2.4%) were the most common neurological diagnoses among the patients. Even though Covid-19 affects the central and peripheral nervous systems, eliminating the possibility of Covid-19 pneumonia with thorax CT is critical for early treatment and patient prognosis.

Neuroimaging Patterns in Patients with COVID-19-Associated Neurological Complications: A Review.

BACKGROUND: A variety of neuroimaging abnormalities in COVID-19 have been described. OBJECTIVES: In this article, we reviewed the varied neuroimaging patterns in patients with COVID-19-associated neurological complications. METHODS: We searched PubMed, Google Scholar, Scopus and preprint databases (medRxiv and bioRxiv). The search terms we used were "COVID -19 and encephalitis, encephalopathy, neuroimaging or neuroradiology" and "SARS-CoV-2 and encephalitis, encephalopathy, neuroimaging or neuroradiology". RESULTS: Neuroimaging abnormalities are common in old age and patients with comorbidities. Neuroimaging abnormalities are largely vascular in origin. COVID-19-associated coagulopathy results in large vessel occlusion and cerebral venous thrombosis. COVID-19-associated intracerebral hemorrhage resembles anticoagulant associated intracerebral hemorrhage. On neuroimaging, hypoxic-ischemic damage along with hyperimmune reaction against the SARS-COV-2 virus manifests as small vessel disease. Small vessel disease appears as diffuse leukoencephalopathy and widespread microbleeds, and subcortical white matter hyperintensities. Occasionally, gray matter hyperintensity, similar to those observed seen in autoimmune encephalitis, has been noted. In many cases, white matter lesions similar to that in acute disseminated encephalomyelitis have been described. Acute disseminated encephalomyelitis in COVID-19 seems to be a parainfectious event and autoimmune in origin. Many cases of acute necrotizing encephalitis resulting in extensive damage to thalamus and brain stem have been described; cytokine storm has been considered a pathogenic mechanism behind this. None of the neuroimaging abnormalities can provide a clue to the possible pathogenic mechanism. CONCLUSIONS: Periventricular white-matter MR hyperintensity, microbleeds, arterial and venous infarcts, and hemorrhages are apparently distinctive neuroimaging abnormalities in patients with COVID-19.

Neurological complications in COVID-19 - a diagnostic challenge.

With the exponential growth of COVID-19 cases, the neurological complications reported during or after the infection became more common. There is limited knowledge regarding the pathophysiological mechanisms that are responsible for these complications. Recent data provides compelling evidence for the neurotropic nature of SARS-CoV-2, based on neurological manifestations reported during the current pandemic, as well as on previous experience with other coronaviruses. We present the case of a patient who developed headaches, motor deficit and dysphasia after respiratory COVID-19. Imaging tests showed heterogeneous central nervous system lesions (multiple subarachnoid hemorrhages and two ischemic strokes). Given the plethora of atypical neurological complications of COVID-19 described in the current literature, establishing a positive diagnosis and deciding on a treatment plan proved to be particularly challenging. We set to discuss some of the possible pathologies, hypothesized to be associated with COVID-19, that could lead to concomitant neurological lesions, similar to those noticed in our patient.

COVID-19 - neuropathological point of view, pathobiology, and dilemmas after the first year of the pandemic struggle.

This article constitutes a summary of the knowledge on the involvement of the nervous system in COVID-19, concerning its general pathobiology, clinical presentation and neuropathological features as well as the future directions of investigation. Variable definitions, selection bias, mainly retrospective analyses of hospitalized patients and different methodologies are implemented in the research of this new disease. Central nervous system (CNS) pathology presents most frequently features of non-specific neuroinflammation with microglial activation and lymphoid infiltrations, ischemic/hypoxic encephalopathy, acute cerebrovascular disease, and microthrombi. Some brain specimens remain unaffected or show only non-specific changes of the critical status. Interpretations of the neuropathological findings are not always balanced in a clinical context and discrepant in consequence. Designing of longitudinal neuropathological studies, more frequent autopsies, and building of COVID-19 brain banks, together with neuroimaging analyses is essential. Genetic predispositions or immunological factors corresponding to the disease profile as well as cerebrospinal fluid (CSF) or serum biomarkers of COVID-19, the impact of different virus variants and influence of the therapy need to be identified. The mechanisms causing neuroCOVID and cognitive impairment - whether they are infectious, toxic, vascular or metabolic - create other aspects under research. There are also many existential questions about post-COVID and delayed sequelae of the infection. The fight with pandemic is a challenge for the global society, with neuropathologists and neuroscientists as important allies in struggle for understanding and conquering COVID-19.

Neurological issues during severe COVID-19 in a tertiary level hospital in Western India.

BACKGROUND: India has the second largest COVID-19 epidemic in the world as per current estimates. Central and peripheral nervous system involvement in COVID-19 (Neuro COVID-19) has been increasingly identified and reported. This letter is the first report of the spectrum of neurological disorders observed in patients with severe COVID-19 from a resource limited setting like India. Till October 30th 2020, Noble hospital and research center, Pune, India has admitted 2631 patients of COVID-19. Out of these, 423 patients had severe COVID-19. NEUROLOGIC COMPLICATIONS IN SEVERE COVID-19 IN PUNE, INDIA: Of the 423 patients with severe COVID-19, 20 (4.7%) had pre-existing neurologic co-morbidities, with cerebrovascular disease (8 patients) being the most common. Poliomyelitis (4 patients) was also an important co-morbidity associated with severe COVID-19. Bodyache or myalgia (207/423, 49 %) and headache (59/423, 13.9 %) were the most common neurologic symptoms observed in patients. Encephalopathy (22/423, 5.2 %) and new onset large vessel ischemic stroke secondary to cerebral artery thrombosis (5/423, 1.1%) were the most common secondary neurologic complications noted in our cohort. Two cases of COVID-19/central nervous system tuberculosis co-infection were also identified. CHALLENGES IN MANAGEMENT OF NEURO COVID-19 IN INDIA: Various challenges like an overwhelmed health care system, inadequate workforce, lack of exhaustive reporting of symptoms and poor availability of neuroimaging in ventilated COVID-19 patients leads to underestimation of Neuro COVID-19 in resource limited settings like India.

Magnetic Resonance Imaging (MRI) and neurological manifestations in SARS-CoV-2 patients.

OBJECTIVE: The "Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)" disease caused a challenging and threating pandemic (COVID-19) worldwide with a great loss to life and the global economy. SARS-CoV-2 mainly involves the respiratory system, however, with Magnetic Resonance Imaging (MRI), neurological and special senses clinical manifestations have been reported rarely. The present study aims to investigate the MRI findings, clinical manifestations of neurological and special senses involvement in SARS-CoV-2 patients. MATERIALS AND METHODS: In this study, 284 articles from the databases "Pub-Med, Web of Science-Clarivate Analytics, Embase and Google Scholar" were identified. The keywords, coronavirus, SARS-CoV-2, COVID-19 pandemic, MRI, brain, special senses, neurological involvement were entered into the search engines and the concerned documents were selected and reviewed. The descriptive information was recorded from the particular studies; finally, we included 48 publications. RESULTS: The common neurological manifestations in SARS-CoV-2 patients were headache, impaired consciousness, acute cerebrovascular disease, ataxia, tremors, meningitis, encephalitis, cerebral bleeding, subarachnoid hemorrhage, frontal lobe, temporal lobe and intracerebral hematoma, hemiparesis and seizures. However, common special senses manifestations in SARS-CoV-2 patients were olfactory, auditory and gustatory disorders including red eyes, painless monocular visual disturbance, anosmia, ageusia, dysgeusia, dysosmia and hypoacusis. Moreover, the MRI findings identified in SARS-CoV-2 patients were isolated oval-shaped lesion in the corpus callosum, bilateral basal ganglia hemorrhage, ischemic lesions involving the corpus callosum, basal ganglia, cerebellum and vasogenic edema extending to the cerebral peduncles, pons and ventricles. CONCLUSIONS: The neurologic manifestations of SARS-CoV-2 patients are highly variable. The SARS-COV-2 exerts its damaging effects on the nervous system and special senses by developing determinant numerous neurological and special senses' clinical manifestations. Physicians with the help of MRI must rule out the neurological and special senses manifestations among SARS-CoV-2 patients.

The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings.

Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a weekly virtual coronavirus disease 19 (COVID-19) neurology multi-disciplinary meeting was established at the National Hospital, Queen Square, in early March 2020 in order to discuss and begin to understand neurological presentations in patients with suspected COVID-19-related neurological disorders. Detailed clinical and paraclinical data were collected from cases where the diagnosis of COVID-19 was confirmed through RNA PCR, or where the diagnosis was probable/possible according to World Health Organization criteria. Of 43 patients, 29 were SARS-CoV-2 PCR positive and definite, eight probable and six possible. Five major categories emerged: (i) encephalopathies (n = 10) with delirium/psychosis and no distinct MRI or CSF abnormalities, and with 9/10 making a full or partial recovery with supportive care only; (ii) inflammatory CNS syndromes (n = 12) including encephalitis (n = 2, para- or post-infectious), acute disseminated encephalomyelitis (n = 9), with haemorrhage in five, necrosis in one, and myelitis in two, and isolated myelitis (n = 1). Of these, 10 were treated with corticosteroids, and three of these patients also received intravenous immunoglobulin; one made a full recovery, 10 of 12 made a partial recovery, and one patient died; (iii) ischaemic strokes (n = 8) associated with a pro-thrombotic state (four with pulmonary thromboembolism), one of whom died; (iv) peripheral neurological disorders (n = 8), seven with Guillain-Barré syndrome, one with brachial plexopathy, six of eight making a partial and ongoing recovery; and (v) five patients with miscellaneous central disorders who did not fit these categories. SARS-CoV-2 infection is associated with a wide spectrum of neurological syndromes affecting the whole neuraxis, including the cerebral vasculature and, in some cases, responding to immunotherapies. The high incidence of acute disseminated encephalomyelitis, particularly with haemorrhagic change, is striking. This complication was not related to the severity of the respiratory COVID-19 disease. Early recognition, investigation and management of COVID-19-related neurological disease is challenging. Further clinical, neuroradiological, biomarker and neuropathological studies are essential to determine the underlying pathobiological mechanisms that will guide treatment. Longitudinal follow-up studies will be necessary to ascertain the long-term neurological and neuropsychological consequences of this pandemic.

Nervous System Involvement in Coronavirus Disease 2019: Results from a Retrospective Consecutive Neuroimaging Cohort.

Background Neurologic complications in coronavirus disease 2019 (COVID-19) have been described, but the understanding of their pathophysiologic causes and neuroanatomical correlates remains limited. Purpose To report on the frequency and type of neuroradiological findings in COVID-19. Materials and Methods In this retrospective study, all consecutive adult hospitalized patients with polymerase chain reaction positivity for severe acute respiratory syndrome coronavirus 2 and who underwent neuroimaging at Karolinska University Hospital between March 2 and May 24, 2020, were included. All examinations were systematically re-evaluated by 12 readers. Summary descriptive statistics were calculated. Results A total of 185 patients with COVID-19 (62 years ± 14 [standard deviation]; 138 men) underwent neuroimaging. In total, 222 brain CT, 47 brain MRI, and seven spinal MRI examinations were performed. Intra-axial susceptibility abnormalities were the most common finding (29 of 39; 74%, 95% CI: 58, 87) in patients who underwent brain MRI, often with an ovoid shape suggestive of microvascular pathology and with a predilection for the corpus callosum (23 of 39; 59%; 95% CI: 42, 74) and juxtacortical areas (14 of 39; 36%; 95% CI: 21, 53). Ischemic and macrohemorrhagic manifestations were also observed, but vascular imaging did not demonstrate overt abnormalities. Dynamic susceptibility contrast perfusion MRI in 19 patients did not reveal consistent asymmetries between hemispheres or regions. Many patients (18 of 41; 44%; 95% CI: 28, 60) had leukoencephalopathy and one patient had a cytotoxic lesion of the corpus callosum. Other findings included olfactory bulb signal abnormalities (seven of 37; 19%), prominent optic nerve subarachnoid spaces (20 of 36; 56%), and enhancement of the parenchyma (three of 20; 15%), leptomeninges (three of 20; 15%), cranial nerves (two of 20; 10%), and spinal nerves (two of four; 50%). At MRI follow-up, regression of leukoencephalopathy and progressive leptomeningeal enhancement was observed in one patient each, respectively, which is suggestive of dynamic processes. Conclusion Patients with coronavirus disease 2019 had a wide spectrum of vascular and inflammatory involvement of both the central and peripheral nervous system. © RSNA, 2020 Online supplemental material is available for this article.

CSF Biomarkers in Patients With COVID-19 and Neurologic Symptoms: A Case Series.

OBJECTIVE: To explore whether hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and neurologic symptoms have evidence of CNS infection, inflammation, and injury using CSF biomarker measurements. METHODS: We assessed CSF SARS-CoV-2 RNA along with CSF biomarkers of intrathecal inflammation (CSF white blood cell count, neopterin, ß2-microglobulin, and immunoglobulin G index), blood-brain barrier integrity (albumin ratio), and axonal injury (CSF neurofilament light chain protein [NfL]) in 6 patients with moderate to severe coronavirus disease 2019 (COVID-19) and neurologic symptoms who had undergone a diagnostic lumbar puncture. Neurologic symptoms and signs included features of encephalopathies (4 of 6), suspected meningitis (1 of 6), and dysgeusia (1 of 6). SARS-CoV-2 infection was confirmed by real-time PCR analysis of nasopharyngeal swabs. RESULTS: SARS-CoV-2 RNA was detected in the plasma of 2 patients (cycle threshold [Ct] value 35.0-37.0) and in CSF at low levels (Ct 37.2, 38.0, 39.0) in 3 patients in 1 but not in a second real-time PCR assay. CSF neopterin (median 43.0 nmol/L) and ß2-microglobulin (median 3.1 mg/L) were increased in all. Median immunoglobulin G index (0.39), albumin ratio (5.35), and CSF white blood cell count (<3 cells/µL) were normal in all, while CSF NfL was elevated in 2 patients. CONCLUSION: Our results in patients with COVID-19 and neurologic symptoms suggest an unusual pattern of marked CSF inflammation in which soluble markers were increased but white cell response and other immunologic features typical of CNS viral infections were absent. While our initial hypothesis centered on CNS SARS-CoV-2 invasion, we could not convincingly detect SARS-CoV-2 as the underlying driver of CNS inflammation. These features distinguish COVID-19 CSF from other viral CNS infections and raise fundamental questions about the CNS pathobiology of SARS-CoV-2 infection.