key: cord-264052-uph136sn
authors: Wilson, Mitchell P; Jack, Andrew S
title: Coronavirus disease (COVID-19) in neurology and neurosurgery: A scoping review of the early literature
date: 2020-04-23
journal: Clin Neurol Neurosurg
DOI: 10.1016/j.clineuro.2020.105866
sha: 
doc_id: 264052
cord_uid: uph136sn

Coronavirus disease 2019 (COVID-19) is a devastating respiratory illness that has dramatically changed the medical landscape around the world. In parallel with a rise in the number of cases globally, the COVID-19 literature has rapidly expanded with experts around the world disseminating knowledge and collaborating on best practices. To date, the literature has predominantly consisted of case reports, case series, and systemic protocols for dealing with this deadly disease from a plethora of specialties with larger observational and randomized studies only now starting to emerge. This scoping review of MEDLINE, EMBASE, SCOPUS, and the Cochrane Library aims to evaluate and summarize the current status of the COVID-19 literature at it applies to neurology and neurosurgery. Neurological symptomatology, neurological risk factors for poor prognosis, pathophysiology for neuroinvasion, and actions taken by neurological or neurosurgical services to manage the current COVID-19 crisis are reviewed.

Early reports have demonstrated respiratory predominant symptomatology including fever, cough, dyspnea, and fatigue (2) . However, as the prevalence of COVID-19 continues to increase globally, other disease manifestations such as those affecting the central nervous system (CNS) are reported (3) . Furthermore, the emergence of cases involving less commonly afflicted organ systems has necessitated rapid and dramatic changes in practice patterns and has significant implications for all specialties of medicine. This scoping review evaluates the current status of the COVID-19 literature as it relates to neurology and neurosurgery.

The 26-item 2018 PRISMA extension for Scoping Reviews (PRISMA-ScR) checklist was used as an outline for this study (4) . An a priori protocol was not pre-registered. A search of MEDLINE, J o u r n a l P r e -p r o o f EMBASE, Scopus, and the Cochrane Library (including the Cochrane Database of Systematic   Reviews, the Cochrane Central Register of Controlled Trials, and the Cochrane Special Collections) from inception to April 7, 2020 was performed in order to identify articles evaluating both COVID-19 and neurology or neurosurgery. Variations of "COVID" AND "neuro OR brain OR spine OR peripheral nerve" related title/abstract/keywords and medical subject heading terms were performed with individual database search strategies outlined in Table 1 .

No language restrictions were applied. Database searches were combined and duplicates were removed.

Title and abstracts were then reviewed for relevance and articles evaluating COVID-19 with relevance to neurology and/or neurosurgery were reviewed in full text by two authors with 6 and 9 years of experience in the neurosciences. Studies not relating to COVID-19 or the clinical neurosciences were excluded from review. Relevant references were reviewed. Forward searching of key articles was also performed in Google Scholar. A gray literature search of conference abstracts was not performed given the short interval since inception of COVID-19.

Relevant content related to neurological symptomatology, neurological risk factors for poor prognosis, pathophysiology for neurological involvement, and action taken by neurological or neurosurgical services to manage the current COVID-19 crisis was collected. Critical appraisal of individual sources of evidence was not applied given variability of relevant content by study.

Data from each article was extracted into Microsoft Excel v15.14 (Microsoft, Redmond, Washington, USA).

J o u r n a l P r e -p r o o f RESULTS A total of 29 articles were identified from the databases after duplicate removal. Nineteen articles were excluded for lack of relevance to COVID-19 or the clinical neurosciences. A total of 10 articles including 4 articles discussing clinical symptomatology and/or the neuroinvasive potential of SARS-CoV-2 (5-8) and 6 articles discussing recommendations for modified neurosurgical (9-11), stroke (12) , and spine (13) (14) practices during the COVID-19 crisis. Three additional articles discussing neurological symptoms and invasive neurological potential of SARS-CoV-2 were identified through search article references and forward searching (15) (16) (17) .

Neurological symptomatology has been increasingly reported in recent publications. More frequent neurological symptoms can include headache (11-13%), dizziness (8-17%), and altered level of consciousness (8-9%) (5, 15) . Several peripheral nervous system findings are also now reported in up to 5% of cases including include hypogeusia, hyposomia or anosmia, and neuralgia (15) . Less commonly, acute cerebrovascular disease (3%), epilepsy (1%), and ataxia (1%) have also been reported (15) . Although uncommon, background cerebrovascular disease may be a risk factor for poor outcome in COVID-19 patients (5) .

SARS-CoV-2 is a single stranded RNA enveloped virus with an amino acid sequence similar to severe acute respiratory syndrome coronavirus (SARS-CoV) (8) . The virus is believed to use the J o u r n a l P r e -p r o o f angiotensin-converting enzyme 2 (ACE2) receptor for cellular adherence (1). Typically causing respiratory or gastrointestinal disease, these ACE2 receptor epithelial and endothelial cells have been identified throughout the chest and abdomen (18) (19) . Although the expression of ACE2 is low in the brain, autopsy studies have previously demonstrated SARS-CoV particle presence brain tissue (20) . The mechanism of action for SARS-CoV-2 neurological invasion is not yet specified. Several theories have been postulated including: direct invasion, blood circulation pathway, neuronal pathway, hypoxia injury, immune injury/cytokine storm syndromes, ACE2 receptor expression, among others (8,26). As previously described, perhaps the leading current theory is direct seeding and trans-synaptic infiltration via the olfactory nerve or perineuronal cells. This route of invasion has been documented in animal studies for other coronaviruses (27) (28) (29) (30) . For example, experimental studies in transgenic mice injected intra-nasally with SARS-CoV have demonstrated brain entry via the olfactory nerves with subsequent rapid spread to medial brain structures including the medial temporal lobe, basal ganglia, thalami, and midbrain (30) . These findings would be consistent with the limited case report data available to date.

Animal studies of other beta-coronaviruses have also suggested a link with some long-term neurodegenerative diseases (31) . Long-term persistent psychological distress has been shown in SARS survivors (32) . The potential long-term neurodegenerative and psychological effects of COVID-19 have yet to be determined.

COVID-19 has dramatically altered practice patterns around the world. Early studies have been published with experiences and recommendations, predominantly from locations substantially J o u r n a l P r e -p r o o f affected by the COVID-19 crisis including China (9, 12, 13) and Northern Italy (10, 11) . Thus far, early experience and recommendations in neurosurgical (9) (10) (11) 33) , stroke (12) , and spine (13, 14) practices have been reported (Table 2) As an early scoping review of available literature to date, this study has certain limitations. First, symptoms classified as neurological including headache, dizziness, and altered level of consciousness are non-specific with multiple potential causes. These symptoms may relate to an alternative system of origin, may be therapy related, and/or may be of psychosocial origin.

The extent to which these symptoms may impact the practice of neurology and neurosurgery is uncertain. Second, the predominant limitation of this scoping review pertains to limited available early literature. As the number of COVID-19 cases continues to rise dramatically across the world, we anticipate that the literature will also continue to evolve. As the prevalence of COVID-19 increases, more cases reporting rare neurological presentations of COVID-19 are likely to be published. A better understanding of the mechanism and therapeutic options for invasive neurological cases may also evolve. Consensus statements and society guidelines will likely require continual refinement based on emerging COVID-19 specific data.

Finally, optimal practice patterns will likely vary widely with nuanced configurations based on regional prevalence and available health care resources. In order to ensure optimum neurological patient management, ongoing study of treatment algorithms will be essential for updating and adapting these approaches as the COVID-19 pandemic evolves.

FUNDING SUPPORT: None.

Coronavirus infections -more than just the common cold

Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: a systematic review and meta-analysis

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

PRISMA extension for scoping reviews (PRISMA-ScR): Checklist and explanation

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Anesthetic management of endovascular treatment of acute ischemic stroke during COVID-19 pandemic: Consensus statement from the society for neuroscience in anesthesiology & crtitical care (SNACC) endorsed by the society of vascular & interventional neurology (SVIN), society of neurointerventional surgery (SNIS), neurocritical care society (NCS), and European society of minimally invasive neurological therapy (ESMINT)

OR SARS-CoV-2.mp. OR severe acute respiratory syndrome coronavirus 2.mp.) AND (

COVID OR COVID 19 OR [coronavirus AND disease 2019] OR 2019-nCoV OR SARS-CoV-2 OR [severe AND acute AND respiratory AND syndrome AND coronavirus

OR neurology OR neuroscience OR brain OR spine OR

Cochrane Library: COVID AND (neuro* OR brain OR spine OR peripheral nerve OR cerebrospinal fluid Table 1. Search strategy by database. The systematic search was performed on

J o u r n a l P r e -p r o o f  Created a three tier surge level based on factors including: number of community cases, number of COVID-19 positive inpatients, and percentage of staffing shortages  Created a checklist to determine the case urgency and to determine the availability of operating rooms and post-operative beds dependent on needs  Green surge level (1-9 community cases, or <6 COVID-19 positive patients, and no staffing shortages): operate on all emergent, urgent, and elective cases  Yellow surge level (10-99 community cases, or 7-16 COVID-19 positive inpatients, or < 20% staffing shortages): Proceed with emergent and urgent cases. Limit operating room schedule for elective cases over a 3 week period including a 25% reduction in procedural cases and re-assess  Red surge level (> 100 community cases, or > 17 COVID-19 positive inpatients, or > 21% staffing shortages): Proceed with emergent and urgent cases. Limit operating room schedule for elective cases over a 3 week period including a 50% reduction in procedural cases and re-assess  Black surge level (significant assistance needed from outside institutions): Emergent cases only  Created a three tiered coverage plan including two teams and an alternate team for each of four local hospitals  Promoted reduction in people as possible including: increased teleconferencing as able, restricting hospital access to workers over the age of 65, not allowing patient visitors Table 2 . Early experience and recommendations for neurosurgical, stroke, and spine practices during the COVID-19 crisis.