Acute disseminated encephalomyelitis after SARS-CoV-2 infection
Acute disseminated encephalomyelitis (ADEM) is a rare autoimmune disease of the CNS that often after viral infections and mainly affecting children. ADEM is characterized by the onset of multifocal neurologic symptoms, encephalopathy, with brain MRI showing demyelinating abnormalities in the acute phase.1 Coronavirus disease 2019 (COVID-19) is a novel entity caused by the pandemic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which is characterized by influenza-like symptoms, pneumonia, and in severe cases respiratory insufficiency.2 Many neurologic complications occurring in patients with COVID-19 have been described,3 and it has been hypothesized that, in some cases, SARS-CoV-2 might exhibit a neurotropic behavior.4
Results
We report on a 64-year-old woman with a history of vitiligo, hypertension, and monoclonal gammopathy of undetermined significance who developed an influenza-like syndrome in mid-March 2020 that lasted for 2 weeks. The patient also reported the development of smell and taste deficit that rapidly reached anosmia and ageusia. Starting from April 10, the patient developed bilateral vision impairment associated with sensory deficit on her right leg. She reached the emergency department of our hospital and was referred for ophthalmologic evaluation. Visual acuity was hand motion bilaterally, and relative afferent pupillary defect was detected. Ocular motility and fundus examination were unremarkable, whereas visual field test showed profound defects bilaterally. Neurologic examination, performed on hospitalization, showed mild behavioral abnormalities (irritability), headache, bilateral relative afferent pupillary defect, ageusia and anosmia, severe visual loss, right abdominal sensory level, and left-sided lower limb hyper-reflexia with the Babinski sign. The patient underwent a brain and spine MRI scan (figure), with evidence of multiple T1 post-Gd enhancing lesions of the brain, associated with a single spinal cord lesion at the T8 level and with bilateral optic nerve enhancement. A lumbar puncture was performed and showed lymphocytic pleocytosis with 22 cells/mm3 (reference range: 0–5 cells/mm3), mainly represented by CD3+CD4+ T-cells, with mild hyperproteinorrachia (452 mg/L, reference range: 150–450 mg/L), and identical immunoglobulin G oligoclonal bands were present in the CSF and serum (mirror pattern). PCR for SARS-CoV-2 tested negative on nasal swab and positive on CSF sample. The patient's serum tested positive for anti-SARS-CoV-2 immunoglobulin G and negative for antiaquaporin-4 (AQ4) antibody (ab) and antimyelin oligodendrocyte glycoprotein (MOG) ab; the levels of interleukins were not assessed in serum and CSF.
(A–C) Postgadolinium (Gd) T1-weighted (T1w) sequence of the brain in the axial plane showing 6 enhancing lesions (green arrows), most of which with ring enhancement and some of which with nodular enhancement. Incomplete ring enhancement is shown about the right temporal lesion (dashed green arrow). (D–F) T2-weighted (T2w) fat saturated sequence in the coronal plane with evidence of (D) hyperintense signal of the optic nerves bilaterally (white arrows), which is best seen when compared with the normal signal within (E) the optic chiasm and (F) the optic tracts (dashed white arrows). (G) T2w sequence of the thoracic spine in the sagittal plane showing a hyperintense spindle-like T8 lesion, involving less than 2 metameric levels (dashed yellow arrow). (H) Post-Gd T1w sequence of the spine in the axial plane at the level of T8 showing eccentric areas of enhancement respectively located posteriorly to the right and anteriorly to the left (dashed yellow arrow).
ADEM disease was suspected, and high-dose steroids (IV methylprednisolone 1 g/d for 5 days tapered with oral prednisone 75 mg/d) associated with IV immunoglobulins (2 g/kg in 5 days) were administered. The patient reported significant improvement in visual symptoms and progressive recovery of visual acuity. After 14 days of treatment, vision was 20/30 in the right eye and 20/25 in the left eye. Visual-evoked potential showed increased latency in both eyes (p100 wave latency: 114 ms right eye, 120 ms left eye, reference: <100 ms). A follow-up brain MRI scan also showed a partial improvement with a reduction in the number of Gd-enhancing lesions. On April 27, the patient was discharged with oral prednisone tapering.
Discussion
We report a rare case of an immune-mediated CNS disease that occurs after SARS-CoV-2 infection. Phenotypically, the disease resembled an atypical form of neuromyelitis optica spectrum disorder; however, (1) the hyperacute dynamic of the disease, (2) the presence of multiple, synchronous, enhancing brain lesions, (3) the lack of anti-AQ4 or anti-MOG abs, (4) the absence of longitudinally extended transverse myelitis, and (5) the presence of a viral infection preceding the development of neurologic symptoms do not support this hypothesis, favoring ADEM diagnosis.
Since COVID-19 is currently a pandemic disease, neurologists should be aware that autoimmune neurologic complications involving the CNS might occur and should be promptly recognized and treated to reduce permanent neurologic disability.
Appendix Author
References
1.
Pohl D, Alper G, Van Haren K, et al. Acute disseminated encephalomyelitis: updates on an inflammatory CNS syndrome. Neurology 2016;87:S38–S45.
2.
Guan W, Ni Z, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;382:1708–1720.
3.
Helms J, Kremer S, Merdji H, et al. Neurologic features in severe SARS-CoV-2 infection. New Engl J Med Epub 2020 April 15.
4.
Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol Epub 2020 Feb 27.
Information & Authors
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Published In
Neurology® Neuroimmunology & Neuroinflammation
Volume 7 • Number 5 • September 3, 2020
PubMed: 32482781
Copyright
Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Publication History
Received: May 4, 2020
Accepted: May 13, 2020
Published online: June 1, 2020
Published in print: September 3, 2020
Disclosure
G. Novi: received speaker honoraria from Merck, Novartis, and Roche. T. Rossi: reports no disclosures relevant to the manuscript. Enrico Pedemonte: received speaker honoraria or consultation fees from Biogen and Merck-Serono. L. Saitta: reports no disclosures relevant to the manuscript. C. Rolla: reports no disclosures relevant to the manuscript. L. Roccatagliata: reports no disclosures relevant to the manuscript. M. Inglese: received honoraria or consultation fees from Roche, Biogen, Merck-Serono, Novartis, and Genzyme and research grants from NIH, NMSS, FISM, and Teva Neuroscience. D. Farinini: reports no disclosures relevant to the manuscript. Go to Neurology.org/NN for full disclosures.
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We thank Dr. de Belaunde for the comment on our article.1 We believe that positive RT-PCR should be interpreted as a delay in viral clearance—rather than a primary infection—for several reasons:
(1) presence of positive anti-SARS-CoV-2 antibodies indicate that the patient was in the convalescent phase (i.e.: the immune system had enough time to mount a humoral response to the virus); (2) prompt response to i.v. steroids and immunoglobulins suggests the presence of an autoimmune disease; and (3) involvement of specific CNS structures is typical of ADEM disease.
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The author reports no relevant disclosures. Contact [email protected] for full disclosures.
Reference
I read the article by Novi et al.1 with interest. The positive reverse transcription polymerase chain reaction (RT-PCR) would seem to suggest active CNS infection by COVID-19. It would, thus, seem better to characterize this as infectious meningitis-encephalomyelitis.
Disclosure
For disclosures, please contact the editorial office at [email protected].
Reference
Novi et al.1 presented a nice and informative case. The small-sized lesions with restricted diffusion in MRI might be consistent with ischemic lesions because of vasculitis. High protein and oligoclonal band in CSF could also be present in vasculitis. The presence of optic neuritis and cord lesions is possible in vasculitis.2 Investigations are needed—like MRA-brain and serum-ANCA (Antineutrophil cytoplasmic Antibodies)—to exclude probable vasculitis.3 It is well known that definite vasculitis is diagnosed by brain biopsy.3 The binding of COVID-19 to the ACEI2 (Angiotensin Converting Enzyme Inhibitor-2) that is expressed in several organs—especially in endothelial cells—may lead to endothelialitis.4 Vasculitis is common in late adult and female patients while ADEM is common in young and male patients.2 Vasculitis is another Differential Diagnosis in this case.
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For disclosures, please contact the editorial office at [email protected].
References