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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 9  |  Issue : 2  |  Page : 77-81

SARS-CoV-2 infection-related acute parkinsonism and encephalitis: Is there a clinicoradiological correlation?


Department of Neurology, Gleneagles Global Health City, Chennai, Tamil Nadu, India

Date of Submission27-Nov-2021
Date of Acceptance18-Jul-2022
Date of Web Publication01-Sep-2022

Correspondence Address:
Vikash Agarwal
4C, BBCL Ananya, 17/34 Five Furlong Road, Guindy, Chennai - 600 032, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jnbs.jnbs_45_21

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  Abstract 


COVID-19 infection can cause neurological manifestations as early and late complications (chronic COVID syndrome). These include headache, dizziness, confusion, acute cerebrovascular problems, ataxia, and seizures. COVID-19-related encephalopathy, encephalitis, and parkinsonism have been reported earlier; however, the possible links and pathophysiological mechanisms are unclear. In this report, we report a series of patients (n = 5) presenting with acute severe neurological syndromes such as parkinsonism, focal status epilepticus, or acute ataxia as a part of long-hauler COVID-19 infection. We categorized the clinico-radiological and electroencephalographic features in our cases to understand the clinical patterns in SARS-CoV-2 related brain cortex involvement. This might help in future for better clinical categorization for these COVID-19-related neurological manifestations.

Keywords: COVID-19, encephalopathy, parkinsonism


How to cite this article:
Agarwal V, Mushahary D, Chander P, Venkatraman K, Lakshminarayanan K, Kumar V S, Nayak S D. SARS-CoV-2 infection-related acute parkinsonism and encephalitis: Is there a clinicoradiological correlation?. J Neurobehav Sci 2022;9:77-81

How to cite this URL:
Agarwal V, Mushahary D, Chander P, Venkatraman K, Lakshminarayanan K, Kumar V S, Nayak S D. SARS-CoV-2 infection-related acute parkinsonism and encephalitis: Is there a clinicoradiological correlation?. J Neurobehav Sci [serial online] 2022 [cited 2022 Sep 30];9:77-81. Available from: http://www.jnbsjournal.com/text.asp?2022/9/2/77/355256




  Introduction Top


COVID-19 infection presents with various symptoms, including nonproductive cough, fever, myalgia, fatigue, dyspnea, diarrhea, and nausea/vomiting, while some patients are known to be asymptomatic.[1] COVID-19 infection can cause neurological manifestations as an early presentation such as confusion, anosmia, and ageusia.[2],[3] A systemic review of COVID-19-related publications demonstrated a high likelihood of neurological manifestations in severe COVID-19 infection.[4] Mao et al. found central nervous system (CNS) manifestations in 25% of cases mainly presenting as headache (13%), dizziness (17%), impaired consciousness (8%), acute cerebrovascular problems (3%), ataxia (0.5%), and seizures (0.5%).

COVID-19-related encephalopathy and acute parkinsonism have been reported earlier.[5] However, the possible links and pathophysiological mechanisms are unclear. Proposed hypotheses include neurotropism of COVID-19 virus, basal ganglia lesions in a setting of COVID-19-induced thromboembolic encephalopathy, angiotensin-converting enzyme 2 (AEC2) receptor expression, SARS-CoV-2 proteins-related human protein dysfunction causing protein misfolding, and aggregation. COVID-19 pandemic could affect patients suffering from Parkinson's disease with worsening of both motor and nonmotor symptoms.[6] Long-hauler COVID-19 or chronic COVID syndrome can cause various CNS presentations which can be more disabling.[7]

In this report, we detailed a series of patients (n = 5) presenting with acute severe neurological syndromes such as parkinsonism, focal status epilepticus, or acute ataxia as a part of long-hauler COVID-19 infection.


  Case Reports Top


All five patients presented as a cluster within few days of each other in June 2021 following COVID-19 infection as part of the second wave, which affected the city from where the patients belong. Two patients had acute-onset akinetic-bradykinesia syndrome with T2/FLAIR caudate hyperintensity on magnetic resonance imaging (MRI), two others presented with encephalopathy, focal status epilepticus, and periodic lateralized epileptic discharges (PLEDs) in electroencephalographic (EEG), and one patient had acute-onset cerebellar ataxia. Raised cerebrospinal fluid (CSF) protein with no or minimal cellular response was found in all the patients except one. The patients and their symptoms have been described here in group-wise categories.

Group 1

Acute-onset akinesia bradykinesia syndrome (Cases 1 and 2)

Case 1

A 71-year-old male, diabetic, systemic hypertensive, presented with dysarthria, left-sided slowing of movements, and confusional state. On examination, he had grade 3/4 rigidity in all four limbs and also neck rigidity of 3/4. The blink rate was reduced with hypomimia. He developed stimulus-sensitive myoclonus, which was more prominent over the right upper limb, especially on arousal. The myoclonus showed habituation on repeated stimulus. Computed tomography (CT) chest COVID severity score was 12/25. MRI brain showed asymmetrical FLAIR hyperintensity with mild diffusion-weighted images (DWIs) restriction in bilateral caudate and lentiform nucleus (right side more affected than left) along with left medial thalamus [Figure 1]a and [Figure 1]b. CSF analysis showed proteins 111 mg% and 1 neutrophil without any fungal elements. He received a course of intravenous (IV) immunoglobulin 2 g/kg over 5 days. Over the next several weeks, the patient remained encephalopathic with persistent parkinsonism without any significant clinical improvement.
Figure 1: MRI Brain Changes showing specific areas of involvement

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Table 1: Clinical, demographic and radiological data with outcomes

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Case 2

A sixtynine year old male, who is a known case of ischemic heart disease, diabetes and hypertension developed sudden onset of headache and slowness of all activities of daily living with difficulty in walking. His examination showed bradykinesia on finger tapping, body bradykinesia along with finger–nose test impairment bilaterally [Video 1]. MRI brain showed T2/FLAIR hyperintensity in bilateral caudate and mesial frontal and opercular regions with mild DWI restriction [Figure 1]c. CSF analysis showed proteins 61 mg% with acellularity. He was treated with levodopa 400 mg per day with mild improvement in bradykinesia. However, his overall clinical status remained static. His positron emission tomography scan was done to rule out a paraneoplastic association and showed no evidence of metabolic active tissue in the viscera.



Group 2

Acute encephalitis with focal status epilepticus (Cases 3 and 4)

Case 3

An 86-year-old female, diabetic, hypertensive, and having ischemic heart disease, presented with a fall and comatose state 1 month post-COVID-19 infection. After 3 days of admission, she developed focal right hemiclonic status epilepticus, which needed intubation and IV anesthetic agents. MRI brain showed diffusion restriction in the left insular cortex and mild on the right insular cortex, mesial frontal lobe, and hippocampus along with perimesencephalic subarachonid hemorrhage [Figure 1]d and [Figure 1]e. CT angiography of the brain did not reveal any vascular malformation. CSF analysis showed proteins 240 mg%, 91 cells (mononuclear/PMN) with negative HSV DNA polymerase chain reaction (PCR). Both CSF and serum autoimmune encephalitis panels were negative. EEG showed PLEDs over the temporal region [Figure 2]a and [Figure 2]b. She was treated with acyclovir and IV methylprednisolone pulse (1 g/day for 5 days). She continued to worsen clinically in the intensive care unit and expired due to secondary sepsis and cardiac arrest.
Figure 2: EEG epochs showing PLEDs

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Case 4

A 65-year-old male, history of recurrent stroke (temporal lobe and right thalamic hemorrhage), hypertension, postdecompression, post-COVID-19 infection status, presented with right-sided hemiclonic seizures and status epilepticus. MRI brain showed diffusion restrictions in the left paramedian frontal and left mesial temporal (hippocampal head and body) [Figure 1]f. CSF analysis showed 25-mg proteins with six neutrophils, HSV DNA PCR test was negative. EEG showed PLEDs over the temporal region [Figure 2]c and [Figure 2]d. His C-reactive protein was 204. He continued to be encephalopathic and 4 days after admission, he had sudden bradycardia and desaturation and could not be revived.

Group 3

Acute cerebellar ataxia with headache (Case 5)

Case 5

A fifity two year old diabetic presented with history of acute onset difficulty in walking since one month after a mild COVID-19 infection(which was treated at home based covid care). CT chest showed a CT severity score of 5/25. MRI brain was normal, Vitamin B12 >2000 units. CSF analysis showed CSF protein was 81 mg% with 1 cell (lympho or PMN). CSF Gene XPERT MTB, culture, and fungal smear were negative. He was treated symptomatically and remains stable on follow-up.


  Discussion Top


We described three groups of acute CNS manifestations of long-hauler COVID-19. All cases had a mild COVID infection 3–6 weeks before the neurological presentation along with multiple comorbidities, namely diabetes, hypertension or prior stroke, and showed MRI changes (except one case), with raised CSF proteins. We correlated the MRI changes with clinical presentation and associated findings.

The cases described in group 1 presented with post-COVID-19 infection acute parkinsonism and myoclonus with bilateral caudate hyperintensity and raised CSF protein. There was no history of prior parkinsonism in these cases or any suggestion of prodromal PD. A previous case described in the literature with akinetic-rigid syndrome, myoclonus, and DaT-single-photon emission computed tomography confirmed bilateral decrease in presynaptic dopamine uptake asymmetrically involving both putamina has drawn attention to post-COVID-19 parkinsonism with much skepticism.[8] Our first patient had similar myoclonus as reported in the previous case; however, the patient did not show any clinical improvement. It has been suggested by Lang et al. that the stress of SARS-CoV-2 infection could have unmasked a prodromal Parkinsons's disease and the acute parkinsonism could represent a preexisting nigrostriatal dysfunction.[9] We could not do the nuclear imaging studies in our cases which could have highlighted this viewpoint.

On analyzing the patterns in the MRI findings in correlation with the clinical syndrome, group 1 with acute parkinsonism showed bilateral caudate involvement on initial presentation and only later involvement of the extra basal ganglia regions (like mesial frontal in case number 2). However, group 2 showed a typical insulomesial frontal-hippocampal involvement in both cases. This finding may suggest a likelihood of limbic system involvement when the clinical presentation is encephalitis with focal status epilepticus. However, this observation needs more data with a larger sample size. A case of acute necrotizing encephalopathy has been described in relation to COVID-19 infection.[10] Similar case reports of acute disseminated encephalitis (acute disseminated encephalomyelitis) or ataxia have been reported.[11],[12] The CNS injury is presumed to be due to a cytokine storm-mediated tissue damage; however, the degree of the severity of SARS-CoV-2 in our cases was mild. It can be postulated that the presence of comorbidities such as diabetes (which was present in all cases) or hypertension has made the CNS more vulnerable for an immune-mediated or a direct tissue injury subsequently with breach of the blood–brain barrier integrity. Immunotherapy has not altered the clinical course significantly in our cases. This may suggest that the pathophysiological mechanisms of SARS-CoV-2 brain injury are complex and needs further research. There is a need to develop standard treatment protocols in SARS-CoV-2-related CNS manifestations including the degree of intervention by immunotherapy.


  Conclusion Top


Acute severe neurological syndromes such as parkinsonism, focal status epilepticus, or acute ataxia can be a part of long-hauler COVID-19 infection. These presentations have specific MRI findings in brain regions (such as the limbic system, mesial frontal, and basal ganglia) and show EEG changes with raised CSF proteins with variable clinical outcomes. There is a need for further studies in these specific subgroups which will help in better understanding of the role of future treatments including immunotherapy in long-hauler COVID-19 infection.

Patient informed consent

Patient informed consent was obtained.

Ethics committee approval

There is no need for ethics committee approval.

Conflict of interest

There is no conflict of interest to declare.

Financial support and sponsorship

No funding was received.

Author contribution subject and rate

  • Vikash Agarwal (30%): Clinical concept and manuscript write up.
  • Dolly Mushahary (10%): Technical support.
  • Praveen Chander (10%): Clinical concept.
  • Venkatraman.K (10%): Article review.
  • Lakshminarayanan.K (10%): Article review.
  • Sathish Kumar .V (10%): Article Review.
  • S.Dinesh Nayak (20%): Clinical Concept.




 
  References Top

1.
Niazkar M, Niazkar HR. COVID-19 outbreak: Application of multi-gene genetic programming to country-based prediction models. Electronic J Gen Med 2020;17:em247. https://doi.org/10.29333/ejgm/8232.  Back to cited text no. 1
    
2.
Jiang F, Deng L, Zhang L, Cai Y, Cheung CW, Xia Z. Review of the clinical characteristics of coronavirus disease 2019 (COVID-19). J Gen Intern Med 2020;35:1545-9.  Back to cited text no. 2
    
3.
Niazkar HR, Zibaee B, Nasimi A, Bahri N. The neurological manifestations of COVID-19: A review article. Neurol Sci 2020;41:1667-71.  Back to cited text no. 3
    
4.
Asadi-Pooyaa AA, Simanic L. Central nervous system manifestations of COVID-19: A systematic review. J Neurol Sci 2020;413:116832.  Back to cited text no. 4
    
5.
Sulzer D, Antonini A, Leta V, Nordvig A, Smeyne RJ, Goldman JE, et al. COVID-19 and possible links with Parkinson's disease and parkinsonism: From bench to bedside. NPJ Parkinsons Dis 2020;6:18.  Back to cited text no. 5
    
6.
Cilia R, Bonvegna S, Straccia G, Andreasi NG, Elia AE, Romito LM, et al. Effects of COVID-19 on Parkinson's disease clinical features: A community-based case-control study. Mov Disord 2020;35:1287-92.  Back to cited text no. 6
    
7.
Baig AM. Deleterious outcomes in long-hauler COVID-19: The effects of SARS-CoV2 on the CNS in chronic COVID syndrome. ACS Chem Neurosci 2020;11:4017-20.  Back to cited text no. 7
    
8.
Méndez-Guerrero A, Laespada-García MI, Gómez-Grande A, Ruiz-Ortiz M, Blanco-Palmero VA, Azcarate-Diaz FJ, et al. Acute hypokinetic-rigid syndrome following SARSCoV-2 infection. Neurology 2020;95:e2109-18.  Back to cited text no. 8
    
9.
Gonzalez-Latapi P, Fearon C, Fasano A, Lang AE. Parkinson's disease andCOVID-19: Do we need to be more patient? Mov Disord 2021;36:277.  Back to cited text no. 9
    
10.
Poyiadji N, Shahin G, Noujaim D, Stone M, Patel S, Griffith B. COVID-19-associated acute hemorrhagic necrotizing encephalopathy: Imaging features. Radiology 2020;296:E119-20.  Back to cited text no. 10
    
11.
Baig AM. Neurological manifestations in COVID-19 caused by SARS-CoV-2. CNS Neurosci Therapeut 2020;26:499-501.  Back to cited text no. 11
    
12.
McAbee GN, Brosgol Y, Pavlakis S, Agha R, Gaffoor M. Encephalitis associated with COVID-19 infection in an 11 year-old child. Pediatr Neurol 2020;109:94.  Back to cited text no. 12
    


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