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BRIEF REPORT
Year : 2020  |  Volume : 68  |  Issue : 5  |  Page : 1192-1195

Acute Demyelinating Encephalomyelitis (ADEM) in COVID-19 Infection: A Case Series


1 Department of Family Practice, Univ of Minnesota, Minneapolis, United States
2 Minneapolis Clinic of Neurology, Minneapolis, United States
3 Minneapolis Radiology, Plymouth, MN, United States

Date of Web Publication27-Oct-2020

Correspondence Address:
Prof. Praful Kelkar
Minneapolis Clinic of Neurology, Golden Valley, MN - 55422
United States
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.299174

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 » Abstract 


Objective: The purpose of this study was to report three patients COVID-19 infection with severe respiratory syndrome requiring intubation, who developed acute demyelinating encephalomyelitis (ADEM).
Methods: Patient data were obtained from medical records from the North Memorial Hospital, Robbinsdale, MN, USA.
Results: Three patients (two men and one woman, aged 38–63) presented with fatigue, cough, and fever leading to acute respiratory distress syndrome secondary to COVID-19 infection requiring ventilatory support. Two patients were unresponsive and the third patient had severe diffuse weakness. MRI in all patients showed findings consistent with ADEM. CSF showed elevated protein in all patients with normal cell count and no evidence of infection, including negative COVID-19 PCR. All three patients were treated with intravenous corticosteroids and one improved markedly. The other two had minimal response to steroids and no further improvement after IVIG.
Conclusion: Neurological complications from COVID-19 are being rapidly recognized. Our three cases highlight the occurrence of ADEM as a postinfectious/immune-mediated complication of COVID-19 infection, which may be responsive to corticosteroid treatment.


Keywords: Acute demyelinating encephalomyelitis (ADEM), Covid-19, SARS-Cov-2
Key Message: ADEM (acute demyelinating encephalomyelitis) can occur in patients with severe Covid-19 infection, with increased complications and morbidity. Early recognition and treatment with corticosteroids may be beneficial.


How to cite this article:
McCuddy M, Kelkar P, Zhao Y, Wicklund D. Acute Demyelinating Encephalomyelitis (ADEM) in COVID-19 Infection: A Case Series. Neurol India 2020;68:1192-5

How to cite this URL:
McCuddy M, Kelkar P, Zhao Y, Wicklund D. Acute Demyelinating Encephalomyelitis (ADEM) in COVID-19 Infection: A Case Series. Neurol India [serial online] 2020 [cited 2020 Dec 4];68:1192-5. Available from: https://www.neurologyindia.com/text.asp?2020/68/5/1192/299174




Acute disseminated encephalomyelitis (ADEM) is a rare, immune-mediated, demyelinating disorder of the central nervous system. It is usually monophasic, characterized by acute encephalopathy with neurologic deficits and brain MRI findings consistent with multifocal demyelination. ADEM is a postinfectious/immune-mediated complication usually following infections, with the highest incidence in the pediatric population. Dating back to the 18th century, it has been associated primarily with viral pathogens including measles, mumps, and rubella.[1] More recently, it has been described in association with Middle East respiratory syndrome coronavirus and Coronavirus OC43.[2]

With the backdrop of the current COVID-19 pandemic, various neurologic complications are being reported.[3] ADEM secondary to COVID-19 has been described in only one prior patient to date.[4] Two cases of brain and spinal cord demyelination were also reported.[5],[6] We present a series of three adult patients from one medical center with severe COVID-19 infection with acute respiratory failure requiring intubation, who developed neurological complications with MRI changes indicative of ADEM.


 » Method Top


Patient data were obtained from medical records from the North Memorial Hospital, Robbinsdale, MN, USA.


 » Results Top


We report three adult patients who developed ADEM as a complication of severe COVID-19 infection[Table 1]. Two were males and one female with ages between 38 and 70 years. The common concomitant illness was diabetes mellitus. All three patients presented with fatigue, cough, and fever leading to development of acute respiratory distress syndrome secondary to COVID-19 infection requiring ventilatory support. They were intubated for 16–32 days and were diagnosed with ADEM during the third week of the illness. Neurological presentation consisted of encephalopathy postextubation with unresponsiveness in two patients, with eye deviation to the left in one. The third patient developed severe diffuse weakness with hyperreflexia.
Table 1: Clinical characteristics, MRI and laboratory findings, and outcome in three patients with Covid-19 infection-related ADEM

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Brain MRI [Figure 1] in all three cases showed multiple T2 hyperintense lesions distributed predominantly in the white matter, many showing restricted diffusion. These were bilateral and asymmetric; small, round to oval, and with somewhat indistinct margins. The lesions were in the deep and periventricular white matter with involvement of corpus callosum and brainstem. Minimal enhancement was seen in a few lesions. There was little if any disease in the basal ganglia or thalami. There was no associated hemorrhage.
Figure 1: MRI findings in three patients showing multifocal T2 hyperintense lesions with restricted diffusion involving the corpus callosum, bilateral cerebral white matter, and brainstem with some enhancement. A = Diffusion (DWI); B = T2 FLAIR; C = Fat-suppressed T2; D = Postcontrast T1; and E = Noncontrast T1.

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CSF showed elevated protein 55–95 mg/dL with normal cell count. Cultures and encephalitis/meningitis panels, oligoclonal bands, and IgG index were negative in all cases. CSF COVID-19 PCR was negative in all cases, whereas serum PCR was positive for COVID-19 in all.

All three patients received convalescent plasma treatment for COVID-19, and IV steroids (solumedrol in 2 and dexamethasone in 1) and two received IVIG. Following steroid infusions Patient 1 improved markedly. Patients 2 and 3 both demonstrated mild improvement on MRI findings, although their neurologic change was minimal. These two patients also received IVIG dosed at 0.4 g/kg for 3 days with no further improvement.


 » Discussion Top


There are increasing reports of neurologic manifestations of COVID-19 infection. The incidence of CNS symptoms is shown to be as high as 40% in patients with severe infection.[3],[7] Ischemic strokes, encephalopathy, meningitis, encephalitis, Guillain Barre syndrome or Miller–Fisher syndrome and acute hemorrhagic necrotizing encephalopathy have been described.[3],[7],[8]

ADEM due to Covid-19 was previously described in one patient.[4] MRI findings suggestive of demyelination were reported in two other recent cases.[5],[6] We now describe a series of three patients with severe Covid-19 infection who developed ADEM. All these patients were intubated for respiratory failure.

Magnetic resonance is the preferred imaging modality in assessment of suspected cases. CT scans were unremarkable in all patients, and MRI showed findings indicative of ADEM. Characteristic T2 hyperintense lesions were small, round to oval with somewhat indistinct margins, and many had restricted diffusion. The distribution and morphology of the lesions were not typical for acute embolic infarcts. None had history of preexisting demyelinating disorder such as multiple sclerosis, which can have a similar appearance. The relative lack of enhancement and negative CSF panels argue against infectious.

All three patients underwent thorough investigation to rule out other causes of CNS involvement. CSF in all three patients showed elevated protein with normal WBC count and negative oligoclonal bands. CSF cultures, meningitis/encephalitis panels, MS panels, and tests for Lyme & syphilis were negative. All patients also had negative COVID-19 PCR of CSF; thus, there was no evidence of direct CNS involvement by the SARS-CoV-2 coronavirus. Findings were overall consistent with an immune-mediated process. A common comorbidity in all three patients was diabetes mellitus.

All three patients received IV steroids and two also received IVIG. Patient 1 had significant improvement with return of strength in upper extremities and improved function in lower extremities. Patients 2 and 3 both demonstrated mild interval improvement on MRI findings after IV Solumedrol, but minimal neurologic changes, and no further changes after IVIG treatment.

The acute encephalopathy and multifocal neurologic deficits seen in ADEM have the potential to compound the morbidity in patients with severe COVID-19 infections, prolong hospitalizations, and lead to long-term neurologic deficits. It is thought that the proinflammatory state induced by the cytokine storm may be responsible for the glial cell activation and subsequent demyelination. As such, the accurate diagnosis and timely treatment of ADEM in these patients is of significant clinical importance. There are no randomized studies for ADEM treatment. When treated with high dose corticosteroids (Methylprednisolone is considered first-line) in the acute phase, ADEM has a reported 50–80% rate of full recovery. IVIG and plasma exchange are considered second line therapies.[1] Use of plasma exchange is limited by the potential to exacerbate hemodynamic instability, risk of infection, and potential to decrease the protective antibodies that may help to fight COVID-19. IVIG can increase the risk of thromboembolic adverse events in COVID-19 patients, who already are at increased risk for hypercoagulability.[9]

The question of the safety of corticosteroid use in COVID-19 remains a matter of debate. There is concern that steroid use can augment viral replication, while steroids also have the capacity to modulate the inflammatory response responsible for many of the severe complications of this infection. Given the lack of current clinical evidence for or against steroid use, best clinical judgment should be used when treating COVID-19-associated ADEM and corticosteroid therapy should not be disregarded when profound neurologic deficits have the potential to undermine all other treatment efforts. None of the patients in our series had any adverse effects from IV steroid treatment.

In summary, clinicians need to be aware of the potential for ADEM in acutely ill COVID-19 patients. Unexplained unresponsiveness, weakness, or development of focal central neurological signs should alert clinicians to this possibility. MRI findings are characteristic and helpful in making the diagnosis. Treatment with corticosteroids should be considered in these patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

1.
Pohl JD, Alper FG, Van Haren LK, Kornberg AJ, Lucchinetti CF, Tenembaum S, et al. Acute disseminated encephalomyelitis: Updates on an inflammatory CNS syndrome. Neurology2016;87:S38-45.  Back to cited text no. 1
    
2.
Millichap J. Coronavirus and ADEM. Pediatric Neurology Briefs 2004;18:2. 10.15844/pedneurbriefs-18-1-2.  Back to cited text no. 2
    
3.
Mao L, Jin H, Wang M, He Q, Chang J, Hong C, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol2020;77:683-90.  Back to cited text no. 3
    
4.
Zhang T, Rodricks MB, Hirsh E. COVID-19-Associated acute disseminated encephalomyelitis: A case report. medRxiv ; doi: 10.1101/2020.04.16.20068148.  Back to cited text no. 4
    
5.
Brun G, Hak JF, Coze S, Kaphan E, Curvelli J, Girard N, et al. Demyelination or small-vessel vasculitis? COVID-19—White matter and globus pallidum lesions. Neurol Neuroimmunol Neuroinflamm 2020;7:e777.  Back to cited text no. 5
    
6.
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 2020;4:1-4.  Back to cited text no. 6
    
7.
Ahmad I, Rathore FA. Neurological manifestations and complications of COVID-19: A literature review. J Clin Neurosci 2020;77:8-12.  Back to cited text no. 7
    
8.
Paybast S, Emami A, Koosha M, Baghalha F. Novel coronavirus disease (COVID-19) and central nervous system complications: What neurologist need to know. Acta Neurol Taiwan 2020;29:24-31.  Back to cited text no. 8
    
9.
Panigada M, Bottino B, Tagliabue P, Grasselli G, Novembrino C, Chantarangkul V, et al. Hypercoagulability of COVID-19 patients in intensive care unit. A report of thromboelastography findings and other parameters of hemostasis. J Thromb Haemost 2020;18:1738-42.  Back to cited text no. 9
    


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