Dr. Rachel Brown and Dr. Michael Zandi, members of the University College of London Queen Square National Hospital for Neurology and Neurosurgery COVID-19 Study Group, have published a peer-reviewed article in the journal Brain. The researchers describe their study of patients with disorders of the brain and nerves, including encephalopathies, encephalitis, and Acute Disseminated Encephalomyelitis, ischemic stroke, and nerve disease and SARS-CoV-2 infection. A link to the full article is available here including the supplementary materials with clinical vignettes from the study population.
As the neuroscientist Dr. Adrian Owen from the Western University in Canada summarizes,
“My worry is that we have millions of people with COVID-19 now. And if in a year’s time we have 10 million recovered people, and those people have cognitive deficits ... then that’s going to affect their ability to work and their ability to go about activities of daily living,”
Here is a link to a message from Dr. Adrian Owen and his lab.
Imaging from Patients 12, 13 and 15 (COVID-19 autoimmune and haemorrhagic encephalitis). Axial MRI from three individuals with para-/post-infectious central syndromes. (A–D) Patient 12: axial fluid-attenuated inversion recovery (FLAIR) images show bilateral hyperintensity in the mesial temporal lobes (A and B), hypothalamus (C) temporal lobes and thalamus (D). (E–H) Patient 13: axial T2-weighted (E), diffusion weighted imaging (DWI) (F), susceptibility weighted imaging (SWI) (G) and post-contrast T1-weighted (H) images show multifocal clusters of lesions involving the deep white matter of both cerebral hemispheres, intralesional cyst-like areas of varied sizes, and some peripheral rims of restricted diffusion (F), some haemorrhagic changes (G), and T1 hypointense ‘black holes’ without contrast enhancement (H). (I–P) Patient 15: axial images at the level of the insula and basal ganglia (I–L) and at the level of the temporal lobes and upper pons (M–P). T2-weighted images (I and M), SWI images (J and N), DWI images (K and O) and contrast-enhanced images (L and P). There are extensive confluent areas of T2 hyperintensity (I and M), with haemorrhagic change on SWI imaging (J and N), restricted diffusion on DWI images (K and O) and peripheral contrast-enhancement (arrows in L and P) in the insular region, basal ganglia and left occipital lobe (I–L) as well as in the medial temporal lobes and upper pons (M–P).
ABSTRACT:
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 multidisciplinary 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 prothrombotic 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, which will guide treatment. Longitudinal follow-up studies will be necessary to ascertain the long-term neurological and neuropsychological consequences of this pandemic.
INTRODUCTION:
Since December 2019, almost 10 million cases and 500 000 deaths due to the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have been reported worldwide (WHO situation report). Although the respiratory system complications of coronavirus disease 19 (COVID-19) have been the most frequent and life threatening, there are increasing reports of central and peripheral nervous system (PNS) involvement. These neurological complications have included encephalopathy (Helms et al., 2020), meningo-encephalitis (Moriguchi et al., 2020), ischaemic stroke (Beyrouti et al., 2020), acute necrotizing encephalopathy (Poyiadji et al., 2020), and Guillain-Barré Syndrome (GBS) (Toscano et al., 2020). Radiological series have shown infarcts, microhaemorrhages, features of posterior reversible encephalopathy syndrome, or nerve root enhancement (Franceschi et al., 2020; Mahammedi et al., 2020). Zanin and colleagues (2020) have described a case of CNS demyelination post-COVID-19. Detailed neurological assessment and investigation is challenging in those who are critically ill, limiting the opportunity to delineate the underlying pathophysiology and hence, treatment options. The postulated mechanisms of the various neurological syndromes include, either individually or in combination, direct viral neuronal injury (Zubair et al., 2020), a secondary hyperinflammation syndrome (Mehta et al., 2020), para- and post-infectious inflammatory or immune-mediated disorders, or the effects of a severe systemic disorder with the neurological consequences of sepsis, hyperpyrexia, hypoxia, hypercoagulability and critical illness. Here we describe the detailed emerging spectrum of neurological disorders encountered in 43 COVID-19 patients referred to the National Hospital, Queen Square COVID-19 multidisciplinary team meeting (COVID-MDT), run in partnership with infectious disease and virology colleagues at University College London Hospital (UCLH).
MATERIALS AND METHODS:
We reviewed retrospectively the clinical, radiological, laboratory and neuropathological findings from patients referred to the COVID-MDT neurology/encephalitis and neurovascular multi-disciplinary team meetings. The cases summarized were discussed between 9 April and 15 May 2020. Neurological syndromes developing after definite, probable or possible COVID-19, which were likely to be associated with COVID-19 on clinical grounds, were included. Cases for which a more likely alternative pathology was found were excluded. The probability of COVID-19-related neurological disease was determined using WHO criteria [‘Global surveillance for human infection with coronavirus disease (COVID-19)’]: (i) definite (SARS-CoV-2 RNA PCR positive from nasopharyngeal swab, CSF or pathological specimen); (ii) probable (clinical and laboratory features highly suggestive of COVID-19— lymphopenia, raised D-dimer, suggestive chest radiology in the absence of PCR evidence) (Guan et al., 2020); and (iii) possible, in whom temporal or laboratory features indicate an association but another cause was also found (Ellul et al., 2020). Where possible, laboratory results shown are those nearest to onset of neurological symptoms. The classification of the severity of COVID-19 infection was adapted from Wu and McGoogan (2020). Mild disease included patients with non-pneumonia or mild pneumonia, severe disease included patients with dyspnoea and hypoxia requiring supplementary oxygen, and critical disease included patients with respiratory failure requiring assisted ventilation, septic shock, and/or multi-organ dysfunction. Where possible, laboratory results shown are those nearest to onset of neurological symptoms. Consensus clinical criteria were used to classify individuals with specific neurological syndromes including encephalitis (Solomon et al., 2012; Graus et al., 2016), acute demyelinating encephalomyelitis (ADEM) (Pohl et al., 2016), and GBS (Willison et al., 2016). We obtained assent and/or written consent from patients or from their relatives. This study is approved and registered as a service evaluation of our MDT (ref 06-202021-SE) at University College London Hospitals NHS Trust. Some patient details have been submitted for publication as case reports by their treating physicians: Patients 7 and 11 (Khoo et al., in press), Patient 12 (Zambreanu et al., in press), Patient 15 (Dixon et al., 2020), and Patients 36, 37, 39, 41 and 42 (Beyrouti et al., 2020).
DATA AVAILABILITY:
The data that support the findings of this study are available from the corresponding author, upon reasonable request. The data are not publicly available due to ethical restrictions e.g. their containing information that could compromise the privacy of the patients reported.
RESULTS:
The patients included 24 males and 19 females with ages ranging from 16–85 years. Twenty-three of our patients (53%) were non-white. On the basis of a positive nasal-pharyngeal throat SARS-CoV-2 PCR test, 29 were defined as definite COVID-19, eight were probable and six were possible for this association. The severity of the COVID-19 symptoms varied from mild to critical. The patients presented with a wide range of CNS and PNS features including neuroinflammatory diseases and stroke from 6 days before and up to 27 days following the onset of the COVID-19 symptoms. The patients are divided into five categories based on the clinical, neuroradiological, neurophysiological and laboratory features, as summarized in Table 1. We provide a brief summary of the neurological phenotypes in Tables 2–4. Full details of the clinical, viral, immunological, radiological and neurophysiological investigations, management and treatment responses are detailed in the Supplementary material.