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Table of Contents    
Year : 2021  |  Volume : 69  |  Issue : 5  |  Page : 1424-1426

Catastrophic Presentation of COVID-19 with Solitary Large Denovo Tumefactive Demyelination

1 Department of Neurology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
2 Department of Diagnostic and Interventional Radiology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
3 Department of Transfusion Medicine, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
4 Department of Psychiatry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
5 Department of Internal Medicine, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
6 Department of Microbiology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India

Date of Submission17-Mar-2021
Date of Decision05-May-2021
Date of Acceptance15-May-2021
Date of Web Publication30-Oct-2021

Correspondence Address:
Samhita Panda
Additional Professor and Head, Department of Neurology, All India Institute of Medical Sciences, Jodhpur, Rajasthan
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.329572

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 » Abstract 

Background: The ongoing Coronavirus disease-19 (COVID-19) pandemic has revealed a plethora of extrapulmonary manifestations including neurological presentations. To date, nervous system demyelination has been relatively infrequently reported in this setting. Also, while most data point toward immune activation as a causative process, few studies propound a direct effect.
Case Description: A 35-year-old man presented with severe new-onset headache, hemiparesis, and focal seizures culminating in deeply altered sensorium. Radiological evaluation showed a large expansile demyelinating lesion in the right cerebral hemisphere. Nasopharyngeal swab COVID reverse transcription–polymerase chain reaction (RT-PCR) was positive. After initial non-response to steroids, the patient responded well to plasma exchange leading to complete recovery.
Conclusions: This report highlights a case of active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection presenting with tumefactive demyelination and subsequent response to therapy. It is important to recognize atypical presentations at this juncture as it may be crucial for planning treatment strategies.

Keywords: ADEM, COVID-19, demyelination, plasma exchange, tumefactive
Key Message: Central nervous system demyelination has been sparsely reported in COVID-19, mostly in the post infective period, with small scattered areas of demyelination with variable predilection for enhancement and hemorrhage. Here, atypical presentation of COVID-19 infection with a large tumefactive demyelination is highlighted with treatment challenges.

How to cite this article:
Panda S, Patel P, Jain S, Sharma S, Vegda M, Patel A, Tiwari S, Anne PB, Suthar N, Kumar B, Nag VL. Catastrophic Presentation of COVID-19 with Solitary Large Denovo Tumefactive Demyelination. Neurol India 2021;69:1424-6

How to cite this URL:
Panda S, Patel P, Jain S, Sharma S, Vegda M, Patel A, Tiwari S, Anne PB, Suthar N, Kumar B, Nag VL. Catastrophic Presentation of COVID-19 with Solitary Large Denovo Tumefactive Demyelination. Neurol India [serial online] 2021 [cited 2022 May 25];69:1424-6. Available from: https://www.neurologyindia.com/text.asp?2021/69/5/1424/329572

With the world reeling under the pandemic for more than a year, COVID-19 still remains elusive to robust diagnostic and management strategies. Among the diversity of extrapulmonary manifestations, disorders of peripheral and/or central nervous system (CNS) reported to date include anosmia, ageusia, acute hemorrhagic necrotizing encephalopathy (ANE), encephalopathy, stroke, headache, myalgia, meningitis, encephalitis, seizures, Guillain–Barre syndrome, myelitis, white matter demyelination, and acute disseminated encephalomyelitis (ADEM).[1],[2],[3],[4] Neurotropism and neuroinvasiveness of SARS-CoV-2 virus may be causative with direct invasion as well as indirect hematogenous route being postulated.[5] However, it is still unclear whether the neurological manifestations are a direct effect or indirect immune response to SARS-CoV-2 virus. Here, we report an unusual neurological presentation of COVID-19 and the treatment challenges therein.

 » Case Report Top

A 35-year-old laborer presented with a severe new-onset hemicranial headache and weakness of the left side followed by left focal seizure with prolonged unconsciousness the next day. No antecedent fever, cough, sore throat, anosmia, behavioral change, or visual symptoms were observed. He used cocaine and pheniramine maleate as recreational drugs up to two months prior to the illness. The patient was in deep altered sensorium (GCS- E2V2M4), had left hemiparesis (MRC- 2/5), left facial palsy, generalized hyperreflexia, non-elicitable plantar responses, and was put on a ventilator.

Investigations revealed anemia with leukocytosis, raised erythrocyte sedimentation rate, C-reactive protein, and serum procalcitonin [75 mm at 1 h, 77.53 mg/L, 0.14 ng/mL (normal < 0.02), respectively]. The rest of the biochemical and serological tests were normal. Computed tomography head revealed ill-defined hypodensities in the right fronto-insular region and basal ganglia. Magnetic resonance imaging (MRI) brain showed a large ill-defined lesion in the right fronto-parieto-insular region involving centrum semiovale, external capsule, genu, and body of corpus callosum with extension to the left centrum semiovale, with minimal mass effect but without restricted diffusion, focal microhemorrhage, abnormal parenchymal or leptomeningeal enhancement [Figure 1]. Infratentorial neuroparenchyma and spinal cord and MR spectroscopy was unremarkable. Imaging features were consistent with a large tumefactive demyelinating lesion (TDL). Cerebrospinal fluid (CSF) was clear, under normal pressure, cell count: 2 lymphocytes/mm3, protein: 99 mg/dL, and sugar: 68 (blood sugar: 98 mg/dL) and was negative for bacterial, fungal, and mycobacterial infection and oligoclonal bands. Serology for aquaporin and myelin oligodendrocyte glycoprotein (MOG) antibodies was negative. Visual and brainstem auditory evoked potentials showed normal latencies and electroencephalogram showed mild right-hemispheric background slowing (6–7 Hz theta).
Figure 1: Axial T2-weighted MRI images (a and b) and axial fluid-attenuated inversion recovery (FLAIR) images (c) show abnormal hyperintense signal involving subcortical and deep lobar white matter of the right frontal-parietal-insular region with selective cortical gray matter sparing. Note the involvement of the right basal ganglia, genu, and body of corpus callosum with extension to contralateral side. Axial susceptibility image (d) does not show abnormal blooming. Diffusion-weighted and apparent diffusion coefficient (ADC) images (e and f) do not show diffusion restriction. Lesion appears hypointense on T1-images (g) and does not show post-contrast enhancement (h)

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Nasopharyngeal and throat swabs for COVID RT-PCR were negative on day 1 but the sample repeated on day 3 due to atypical presentation was positive. Serum was negative for Immunoglobulin G (IgG) against SARS-CoV-2 by enzyme-linked immunoassay (ELISA). Chest radiology for cough 1 week later suggested right lower zone atypical pneumonia. An initial 5-day pulse intravenous methylprednisolone did not lead to significant improvement. Considering the potential thrombotic risk of intravenous immunoglobulin (IVIg) in COVID-19, plasma exchange was initiated leading to improvement after the second cycle. At this stage, aggressive and abusive behavior increased sleep latency, and shortened, non-restorative sleep was noted and treated with haloperidol for acute delirium. Gradual clinical improvement was noted—patient becoming lucid and oriented without residual focal deficits by 18 days. He has remained asymptomatic without chronic immunomodulation at 3 months and the MRI of the brain showed significant resolution of the lesion [Figure 2].
Figure 2: Follow-up MRI after 7 weeks. The axial (a and b) and sagittal FLAIR images (c) show significant resolution of signal changes with persistent FLAIR hyperintensity at the body of corpus callosum and left pericallosal white matter (d) Axial T1 image shows complete resolution of previously described hypointense signal changes

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 » Discussion Top

TDL is defined as tumor-like demyelinating lesion larger than 20 mm which may or may not be associated with perilesional edema, mass effect, and/or ring enhancement.[6],[7] TDLs occur as isolated demyelinating events or part of an ongoing inflammatory demyelinating disorder such as multiple sclerosis, neuromyelitis optica spectrum disorder (NMOSD), MOG-associated disorder, ADEM or other autoimmune conditions.[6] They also need to be differentiated from granulomas, vasculitis, infections, abscess, and malignancies. Interestingly, here the isolated TDL was presented in relation to COVID-19 without prior demyelinating illness or preceding COVID-related respiratory issues.

While primarily inflammatory, TDLs may mandate biopsy if clinical and radiological features are atypical. Radiological features favoring TDL currently were preferential white matter involvement, mild mass effect despite extensive involvement including corpus callosum, and relatively preserved N-acetylaspartate (NAA) peak. TDLs, single or multiple, with white more than gray matter involvement, are typically lobar especially in frontoparietal regions apart from basal ganglia, cerebellum, brainstem, and spinal cord.[7] Butterfly lesion of the corpus callosum, as in our patient, is an unusual presentation which needs differentiation from glioblastoma multiforme and primary central nervous system (CNS) lymphoma. The absence of mass effect despite large lesion size, lack of diffusion restriction and contrast enhancement and the absence of raised relative cerebral blood flow within the lesion helped exclude these possibilities. Additionally, ADEM was excluded by the absence of multifocal demyelinating lesions in other areas of the brain and spinal cord while other viral, toxic, drug, and vascular etiologies were also ruled out.

Further, TDL being epicentered at corpus callosum without longitudinally extensive transverse myelitis, brainstem involvement and optic neuritis and absent serological markers were against the diagnosis of NMOSD or MOG-antibody-related disease. While there is a chance of developing MS or NMOSD subsequently, the present investigations did not support any primary demyelinating disorder, although risk stratification and longitudinal follow-up are mandated in view of male gender and younger age.[7]

Demyelinating illness of CNS such as ANE, ADEM, myelitis, or non-specific white matter lesions have been sporadically reported with COVID-19.[1],[3],[4],[8],[9],[10] Mostly, these demyelinating lesions are multiple, small, and scattered T2-hyperintense white matter lesions with variable diffusion restriction and enhancement.[1],[4],[10] Occasional corpus callosal involvement has been noted as in our case though lesional hemorrhage is exceptional.[3],[9],[10] Importantly, catastrophic presentation of TDL with seizures and altered consciousness as a radiologically and clinically isolated event with COVID-19 has not been reported thus far. Moreover, CNS demyelinating events were delayed, in or after the second week, usually after severe COVID-19 infection necessitating intubation due to hyperimmune activation and cytokine storm such that COVID RT-PCR is negative in serum as well as CSF.[1],[4],[10] In the current case, RT-PCR was positive during the presentation while serology was negative for COVID antibodies. Hence, the possibility of SARS-CoV-2 directly triggering the presentation should be considered though there was no pathological evidence.

Intravenous steroids have been used as first-line in demyelinating illness with COVID-19 and IVIg given later with variable response.[1],[4],[10] Both IVIg and plasma exchange may be fraught with complications in active COVID infection. IVIg is known for the risk of thromboembolic events while plasma exchange may lead to hemodynamic instability, electrolyte disturbances, and infections. In our patient, we did not consider COVID-19 as an absolute contraindication to plasma exchange when intravenous methylprednisolone pulse failed. Apart from Zoghi et al., none in the literature reviewed has attempted plasma exchange as a treatment modality.[10]

 » Conclusions Top

This case highlights that SARS-CoV-2 infection can be associated with atypical single, large tumefactive brain demyelination during active infection with plasma exchange as an effective treatment modality.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

 » References Top

Brun G, Hak J-F, Coze S, Kaphan E, Carvelli J, Girard N, et al. COVID-19- White matter and globus pallidum lesions. Demyelination or small-vessel vasculitis? Neurol Neuroimmunol Neuroinflamm 2020;7:e777.  Back to cited text no. 1
Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al. Neurologic manifestations of hospitalized patients with Coronavirus disease 2019 in Wuhan, China. JAMA Neurol 2020;77:683-90.  Back to cited text no. 2
Poyiadji N, Shahin G, Noujaim D, Stone M, Patel S, Griffith B. COVID-19-associated acute haemorrhagic necrotizing encephalopathy: CT and MRI features. Radiology 2020;296:E119-20.  Back to cited text no. 3
Zanin L, Saraceno G, Panciani PP, Renisi G, Signorini L, Migliorati K, et al. SARS-CoV-2 can induce brain and spine demyelinating lesions. Acta Neurochir (Wien) 2020;162:1491-4.  Back to cited text no. 4
Li Z, Liu T, Yang N, Han D, Mi X, Liu K, et al. Neurological manifestations of patients with COVID-19: Potential routes of SARS-CoV-2 neuroinvasion from the periphery to the brain. Front Med 2020;14:533-41.  Back to cited text no. 5
Given II CA, Stevens BS, Lee C. The MRI appearance of tumefactive demyelinating lesions. AJR 2004;182:195-9.  Back to cited text no. 6
Hardy TA, Chataway J. Tumefactive demyelination: An approach to diagnosis and management. J Neurol Neurosurg Psych 2013;84:1047-53.  Back to cited text no. 7
Abdia S, Ghorbanib A, Fatehic F. The association of SARS-CoV-2 infection and acute disseminated encephalomyelitis without prominent clinical pulmonary symptoms. J Neurol Sci 2020;416:117001.  Back to cited text no. 8
Parsons T, Banks S, Bae C, Gelber J, Alahmadi H, Tichauer M. COVID-19-associated acute disseminated encephalomyelitis (ADEM). J Neurol 2020;267:2799-802.  Back to cited text no. 9
Zoghi A, Ramezani M, Roozbeh M, Darazan IA, Sahraian MA. A case of possible atypical demyelinating event of the central nervous system following COVID-19. Mult Scl Rel Dis 2020;44:102324.  Back to cited text no. 10


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