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

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 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.

Keywords: ADEM; COVID-19; SARS-CoV-2; encephalitis.

© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.

Figures

Figure 1

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).

Figure 2

Axial MRI (A–D) and histopathology (E–G) from Patient 17, diagnosed with ADEM, and imaging (H–O) from Patient 16, with combined CNS and PNS disease. (A–G) Patient 17: axial T2-weighted (A), SWI (B), post-gadolinium (C and D) images show extensive confluent ‘tumefactive’ lesions involving the white matter of the right cerebral hemisphere, corpus callosum and corona radiata with mass effect, subfalcine herniation (A), clusters of prominent medullary veins (B, short arrows) and peripheral rim enhancement (D, arrows). (E) The white matter shows scattered small vessels with surrounding infiltrates of neutrophils and occasional foamy macrophages extending into the parenchyma (arrow). The endothelium is focally vacuolated but there is no evidence of vasculitis or fibrinoid vessel wall necrosis in any region. There were a few perivascular T cells in the white matter but the cortex appears normal (not shown). (F) CD68 stain confirms foci of foamy macrophages in the white matter, mainly surrounding small vessels. There was no significant microgliosis in the cortex (not shown). (G) Myelin basic protein stain (SMI94) shows areas with focal myelin debris in macrophages around vessels in the white matter (arrows) in keeping with early myelin breakdown. There is no evidence of axonal damage on neurofilament stain (not shown). Scale bars: E = 45 µm; F and G = 70 µm. (H–O) Patient 16: axial post-gadolinium fat-suppressed T1-weighted images (H) demonstrating pathologically enhancing extradural lumbosacral nerve roots (arrows). Note physiological enhancement of nerve root ganglia (short arrows). Coronal short tau inversion recovery (STIR) image (L) shows hyperintense signal abnormality of the upper trunk of the right brachial plexus (arrow). Initial axial T2 (I and J) and T2*-weighted images (K) show multifocal confluent T2 hyperintense lesions involving internal and external capsules, splenium of corpus callosum (I), and the juxtacortical and deep white matter (J), associated with microhaemorrhages (K, arrows). Follow-up T2-weighted images (M and N) show marked progression of the confluent T2 hyperintense lesions, which involve a large proportion of the juxtacortical and deep white matter, corpus callosum and internal and external capsules. The follow-up SWI image (O) demonstrates not only the previously seen microhaemorrhages (arrows) but also prominent medullary veins (short arrows).

Figure 3

Patients 19 and 20 (ADEM including spinal cord). Patient 19: axial T2 (A and C) and DWI (B and D) images show multifocal lesions involving corpus callosum and corona radiata. Patient 20: axial T2-weighted images of brain MRI and sagittal T2-weighted of the spinal cord acquired on admission (E–H) and after 26 days (I–L). Axial T2-weighted images show multifocal hyperintense lesions in the brainstem (E and I), basal ganglia and supratentorial white matter (F and J). The pontomedullary hyperintensities have become more confluent (I) since admission (E). After 26 days, the signal abnormalities in the basal ganglia and the supratentorial white matter (J) are grossly similar to the baseline MRI scan (F). Sagittal and axial T2-weighted images show diffuse high T2-weighted signal intrinsic to the spinal cord at baseline (G and H). After 26 days, the cord oedema has reduced, and the spinal cord lesions appear less confluent and more discrete (K and L).

Figure 4

Imaging from Patient 27, with cerebral infarction and pulmonary thromboembolism (A–D), and Patient 41, with microhaemorrhages (E–H). (A–D) Patient 27: CT pulmonary angiogram (A) demonstrated large emboli in the right and left pulmonary arteries (arrows). DWI (B), T2-weighted FSE (C) and SWI (D) images show restricted diffusion (B) and T2 hyperintensity (C) in the left basal ganglia and cortical territory of left middle cerebral artery. The SWI image (D) shows haemorrhagic transformation in the basal ganglia (short arrow) and a long intravascular thrombus in a Sylvain branch of the left middle cerebral artery (long arrow). (E–H) Patient 41: chest CT (E) shows severe COVID-19 pneumonitis. SWI images (F–H) demonstrate numerous cerebral microbleeds in the temporal, frontal and parietal lobes, predominantly located at the grey/white matter junction.