Neurological Complications of COVID-19

The neurological complications of COVID-19 are an expansive and heterogeneous topic. This chapter discusses the neuropathophysiology of COVID-19 and the potential mechanisms through which the disease leads to neurological manifestations while also exploring historical viruses that have also led to neurological sequelae. These complications are then characterized and classified into several groups with support from contemporaneous evidence. In addition to this we examine common neurological imaging and their findings and finally discuss the greatest needs moving forward with regard to evidence and research through collaborative efforts. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Eye Disorders and Neuro-ophthalmic Manifestations of COVID-19

Growing data are confirming the association between the novel coronavirus disease (COVID-19) and eye disorders, including ocular alterations and neuro-ophthalmic manifestations. The main pathophysiological mechanisms considered included a direct infection through the ocular surface, a post-viremia secretion of the virus from the lacrimal glands, and a viral dissemination through the bloodstream. According to the different ways of contagion, different structures could be involved.The most common ocular symptoms reported in COVID-19 patients were dry eye, redness, tearing, itching and pain. Among symptomatic patients, most of them presented conjunctivitis. Considering the posterior chamber, retinal artery and vein occlusions were described in few clinical reports;moreover, some studies presented cases of paracentral acute middle maculopathy occurring in COVID-19 patients. The involvement of the choroid seems to be rare, and a single case of atypical choroiditis was currently described. Between neuro-ophthalmic manifestations, optic neuritis appear to be relatively frequent and generally not associated with magnetic resonance imaging abnormalities. Some reports showed the involvement of the ocular motor nerves, often presenting with palsy. Miller Fisher syndrome has been showed in rare cases;however, this association could be corroborated by the several reports describing Guillain-Barré syndrome occurrence in COVID-19 patients.In line with well-known previous viral infection, COVID-19 seems to be associated with eye involvement. Thus, ocular and neuro-ophthalmic symptoms and signs should be carefully assessed and monitored in these patients. To reach this purpose, it is critical to implement remote diagnostic techniques. Moreover, the comprehension of the pathogenetic mechanisms is still scarce and no standardized diagnostic protocol was established for these patients, making necessary further studies to improve current understandings. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Covid-19 and Neuropsychiatry

As the clinical features and potential complications of COVID- 19 emerged last year it became clear that neurological, neuropsychiatric and psychiatric disorders were potentially significant. There were also reasons to expect this from past viral outbreaks, including other severe coronaviruses. The Coro- Nerve study, led by Ben Michael and colleagues, was rapidly set up to as a UK-wide surveillance system for clinicians to initially briefly notify cases and later provide full clinical details. A psychiatry reporting system, led by the RCPsych neuropsychiatry faculty, was added and the first 153 notifications were published last June . The full clinical details of the first 267 cases completed were published as a preprint in January. The has been a rapid growth in the number and quality of publications regarding the neuropsychiatry of COVID-19 and this has been collated on the JNNP Neurology & Neuropsychiatry of COVID-19 blog which we set up to respond to the need for rapid capture and synthesis of a fast moving field with weekly updates and publications from a growing international team, including a recently published preprint systematic review and meta-analysis of the neurology and neuropsychiatry of COVID-19. We will jointly review the CoroNerve data and its context in the emerging wider evidence base regarding the neuropsychiatry of COVID-19, highlighting exciting new research areas such as long COVID and projects such as the recently started COVID-CNS study funded by UKRI. We would like to thank those who have already submitted cases to CoroNerve and encourage others to do the same, including those associated with COVID-19 vaccination, and to flag up that notifying a case and providing data results in pubmed searchable collaborator status on resulting publications.

Global uncertainty in the diagnosis of neurological complications of SARS-CoV-2 infection by both neurologists and non-neurologists: An international inter-observer variability study.

INTRODUCTION: Uniform case definitions are required to ensure harmonised reporting of neurological syndromes associated with SARS-CoV-2. Moreover, it is unclear how clinicians perceive the relative importance of SARS-CoV-2 in neurological syndromes, which risks under- or over-reporting. METHODS: We invited clinicians through global networks, including the World Federation of Neurology, to assess ten anonymised vignettes of SARS-CoV-2 neurological syndromes. Using standardised case definitions, clinicians assigned a diagnosis and ranked association with SARS-CoV-2. We compared diagnostic accuracy and assigned association ranks between different settings and specialties and calculated inter-rater agreement for case definitions as "poor" (κ ≤ 0.4), "moderate" or "good" (κ > 0.6). RESULTS: 1265 diagnoses were assigned by 146 participants from 45 countries on six continents. The highest correct proportion were cerebral venous sinus thrombosis (CVST, 95.8%), Guillain-Barré syndrome (GBS, 92.4%) and headache (91.6%) and the lowest encephalitis (72.8%), psychosis (53.8%) and encephalopathy (43.2%). Diagnostic accuracy was similar between neurologists and non-neurologists (median score 8 vs. 7/10, p = 0.1). Good inter-rater agreement was observed for five diagnoses: cranial neuropathy, headache, myelitis, CVST, and GBS and poor agreement for encephalopathy. In 13% of vignettes, clinicians incorrectly assigned lowest association ranks, regardless of setting and specialty. CONCLUSION: The case definitions can help with reporting of neurological complications of SARS-CoV-2, also in settings with few neurologists. However, encephalopathy, encephalitis, and psychosis were often misdiagnosed, and clinicians underestimated the association with SARS-CoV-2. Future work should refine the case definitions and provide training if global reporting of neurological syndromes associated with SARS-CoV-2 is to be robust.

THE GLOBAL COVID-19 NEURO RESEARCH COALITION

The Global COVID-19 Neuro Research Coalition was formed in May 2020 by 24 expert neurologists and researchers from around the world. Together, they published a call to the global neurology community in The Lancet Neurology to establish a network where members exchange ideas, share research into the intersection of COVID-19 and neurology, and foster communication between international colleagues and institutions, particularly in low- and middle-income countries (LMICs). Now comprising over 100 members from 34 countries, the Coalition works closely with the WHO Neurology and COVID-19 Global Forum to address pressing questions facing neurologists and their patients. In addition to its LMIC focus, the Coalition works to harmonize research networks and strategies, not only for COVID-19, but also for other neurological challenges and future global research. The Coalition has published five papers on diverse topics related to COVID-19 and neurology. These include methodological approaches to understanding neurological associations of COVID-19, support of the WHO Intersectoral Global Action Plan on epilepsy and other neurological disorders, and COVID- 19-associated headache. The Coalition is involved in ongoing reviews into neurological complications of COVID-19 and COVID-19 vaccinations, and as well as studies about accurate diagnoses of these complications and the overall impact of this pandemic on neurological services. It also engages with the WHO-supported Brain Health Clinical Exchange, which invites neurologists around the world to present on relevant neurology topics and engage in interactive discussion. The success of the Global COVID-19 Neuro Research Coalition underlines the need for a platform that brings together the international neurology community in addressing the large burden of neurological disease and shares strategies to face them. With its continent-spanning network of experts, the Coalition will continue to initiate high-quality research that will bring global neurology to the forefront of public health efforts and guide policies that will aid patients everywhere.

Think about it: Neurologic manifestations of COVID-19

In this presentation, Dr Michael will review the results of the clinicoepidemiologic studies of the neurological and neuropsychiatric complications associated with COVID-19, their implications for clinical practice, and insights from on-going studies of underlying disease mechanisms.