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Case Report

Kavya Sindhuri P*, Khutejatul Kubra, Vaidyanathan R, SP Adarsh, Madhusudhan

Cauvery Heart and Multispecialty Hospital, Bannur road, Teresian circle, Mysore–570011.

Corresponding author:

Dr. Kavya Sindhuri P, DNB Anesthesia Resident, Dept. of Anesthesiology and Critical Care, Cauvery Heart and Multispecialty Hospital, Bannur road, Teresian circle, Mysore - 570011. E-mail: kavya.sindhuri9@gmail.com

Affiliated to Rajiv Gandhi University of Health Sciences, Bengaluru, Karnataka.

Received Date: 2021-10-10,
Accepted Date: 2021-11-10,
Published Date: 2021-12-31
Year: 2021, Volume: 1, Issue: 3, Page no. 35-38, DOI: 10.26463/rjahs.1_3_1
Views: 1422, Downloads: 30
Licensing Information:
CC BY NC 4.0 ICON
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0.
Abstract

Coronavirus is a novel human pathogen that caught the world by a storm causing a global pandemic (COVID-19). Developing an effective and reliable vaccine was given the utmost importance. The safety profile and side effects of the new vaccine was always an area of concern for both the scientific community as well as the community at large who were using it. Here, we present a report on a case of suspected acute disseminated encephalomyelitis (ADEM) following vaccination with ChAdOx1 nCoV-19 CoronaVirus Vaccine (Recombinant) COVISHIELD™.

<p class="MsoNormal" style="text-align: justify; line-height: 150%;"><span lang="EN-GB" style="font-family: 'Segoe UI',sans-serif;">Coronavirus is a novel human pathogen that caught the world by a storm causing a global pandemic (COVID-19). Developing an effective and reliable vaccine was given the utmost importance. The safety profile and side effects of the new vaccine was always an area of concern for both the scientific community as well as the community at large who were using it. Here, we present a report on a case of suspected acute disseminated encephalomyelitis (ADEM) following vaccination with ChAdOx1 nCoV-19 CoronaVirus Vaccine (Recombinant) COVISHIELD&trade;. </span></p>
Keywords
ADEM, COVISHIELD™, COVID vaccine, Side effects
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Introduction

COVID-19 pandemic is one of the worst pandemic mankind has ever witnessed. More than two years after the first strain was isolated, it continues to create havoc and has infected over two million people. Worldwide, the most promising long term solution remains the vaccination of the community at a largescale, to prevent re-emergence of novel strains, breaking the transmission and preventing the severity of infection and hospitalization.[1] The safety profile and adverse effects of any newly emerging vaccine has always been questioned, both by the scientific community and the general population.[2] CNS adverse effects following viral vaccines have always been known though the incidence is very less which is 0.1 to 0.2 per 1,00,000 vaccinated individuals.[3,4,5]

Case report

A 19-year-old male patient with status epilepticus was admitted to the ICU, with a history of fever and headache for three days. The patient was in status epilepticus with gaze preference and was managed with Inj. Lorazepam 3 mg and Inj. Fosphen 150 mg. Further neurological assessment was done, and Glasgow coma scale (GCS) were noted after the patient was stabilized and no longer was in status epilepticus. Patient was found to have had no focal neurological deficits and GCS-E1VTM5 with pupils bilaterally equal and reactive. Patient was initiated on ventilator support in view of persisting status epilepticus and impending respiratory failure. On evaluation, complete blood counts revealed severe thrombocytopenia, otherwise unremarkable. He had mildly elevated blood urea and serum creatinine values. His liver function tests (LFT), serum electrolytes were normal. COVID-19 RTPCR was negative. CT brain was unremarkable. A provisional diagnosis of acute viral meningoencephalitis was made, and the patient was started on Inj. Dexamethasone 8 mg TID. Incidentally, he had received his first dose of ChAdOx1 nCoV- 19 Corona Virus Vaccine (Recombinant) COVISHIELD™ three days prior to the onset of symptoms. Cerebrospinal fluid analysis showed normal cell count, normal protein, normal glucose, and was negative for microbial cultures. PCR was sent which returned negative for all the common causative pathogens causing acute meningoencephalitis. The panel tested for 18 pathogens including herpes virus, mycobacterium tuberculosis bacillus species, Japanese enchepalitis virus, pneumococci, meningococcal and other bacteria/virus. The patient improved well and didn’t have any further episodes of seizures and was hemodynamically stable. He was extubated the next day after a successful trial of weaning. MRI brain was done on the same day which, showed bilateral symmetrical T2 and FLAIR hyperintensities (white arrows) with diffusion restriction and blooming on gradient echo sequences (GRE) involving the thalami, the posterior limb of the internal capsule as seen in figure.1.The pontine lesion had not shown diffusion restriction blooming as seen in figure 2,which was suggestive of acute encephalitis or acute disseminated encephalomyelitis (ADEM). Vasculitis and connective tissue workup were negative. The patient improved further, platelet count improved and renal function was stable, and hence was shifted to the ward the following day. He was discharged by day five. He was advised to continue anti-epileptics and steroids. The patient remained free of symptoms during subsequent follow-up and all medications were gradually tapered and stopped.

Discussion

Acute disseminated encephalomyelitis (ADEM) is a demyelinating inflammatory disease characterized by a brief but widespread inflammation in the brain and spinal cord resulting in varied clinical manifestations ranging  from mild focal neurological deficits to coma.3 Most often patients exhibit seizures following a febrile episode, mimicking acute encephalitis. ADEM usually follows viral or bacterial infections. However, rare cases of ADEM have also been reported following vaccination for both viral and bacterial infections with both replicating live vaccines and non-replicating attenuated vaccines.[6] Most of these have been reported after vaccination for measles, mumps, or rubella. However, ADEM has also been associated with vaccines for rabies, diphtheria, tetanus, polio, smallpox, Japanese B encephalitis, pertussis, influenza, hepatitis B.[7,8] In this case report, a similar case of ADEM associated with ChAdOx1 nCoV-19 CoronaVirus Vaccine (Recombinant) [COVISHIELD™] vaccine for COVID-19 was discussed. Considering the not so infrequent association of ADEM with vaccinations, it is not surprising to have come across a case of ADEM following SARSCoV-2 vaccination.[9] ADEM has an estimated annual incidence of 0.8 cases per 100,000 population with a median age of onset of 6.5 years.[5,10] Post-vaccination encephalomyelitis accounts for less than 5% of all the diagnosed cases of ADEM with incidence rates as low as 0.1 to 0.2 per 100,000 vaccinated individuals.[5,10]

 

The presumptive mechanism is said to be immunemediated demyelination and immune-complex mediated vasculopathy.[11] The pathogenesis described was very similar to classical post-infectious demyelination syndromes, which was further confirmed by the fact that the blood samples of the patients with ADEM following vaccination had demonstrable antibodies to gangliosides such as GM1 and GD1a.[12] This is made possible because of the molecular mimicry of antigenic epitopes, shared between an inoculated pathogen or vaccine, and the host CNS protein.[12] Pathologically, a distinct histopathological pattern of ADEM lesions of perivenous inflammation surrounding small vessels in both the CNS grey and white matter is seen. Most of these lesions are infiltrated by lymphocytes, macrophages and neutrophils. Demyelination may not be evident in hyper acute or acute lesions but may develop later in the lesion evolution. There is only a small degree of axonal damage.[5]

Initial symptoms of ADEM develop rapidly beginning with encephalitis-like symptoms including fever, headache, nausea, vomiting, eventually progressing to seizures and coma in severe cases. Patients can also have visual disturbances which may suggest inflammation of the optic nerve (optic neuritis). All the patients usually respond to routine conventional line of treatment for ADEM with steroids and other supportive measures. No permanent neurological deficits or mortality has been reported yet with ADEM following vaccination.

Our patient, a young male was vaccinated with ChAdOx1 nCoV-19 Corona Virus Vaccine (Recombinant) [COVISHIELD™] vaccine for Covid-19 three days prior to hospital admission. This patient developed typical features of encephalitis with high degree fever, nausea, vomiting and seizures. He was started on a standard line of care for acute viral encephalitis with steroids, anticonvulsants and supportive measures. Most common causes of all acute viral encephalitis including herpes encephalitis, dengue encephalitis along with pyogenic meningitis and tubercular meningitis were ruled out with a CSF PCR panel for extended pathogens for acute meningoencephalitis. The patient made a dramatic recovery and was conscious and seizure-free within 48 hours. History of COVID-19 vaccination, rapid deterioration, features of encephalopathy, multifocal neurologic symptoms and an absence of other etiological factors to explain these events coupled with a good response to IV Dexamethasone made us suspect vaccine-related ADEM in this case. The MRI brain findings of bilateral symmetrical T2 and FLAIR hyperintensities involving the thalami and the central pons, were consistent with a clinical diagnosis of ADEM. Hence, a diagnosis of vaccine-related ADEM was made as a diagnosis of exclusion which responded to steroids and conventional management for ADEM. The patient was asymptomatic during subsequent follow-ups and all his medications were stopped after three weeks.

Advanced investigations to look for actual pathology including neuromyelitisoptica (NMO) antibodies, myelin oligodendrocyte glycoprotein (MOG) antibodies and oligoclonal bands in CSF were not done in this case. Similarly, MRI spine to know spinal cord involvement was also not done since patient didn’t had clinical features of spinal cord involvement and improved rapidly.

As per the available evidence, worldwide vaccination for COVID-19 with a variety of vaccines including ChAdOx1 nCoV-19 Corona Virus vaccine (Recombinant) [COVISHIELD™] vaccine has largely been safe without any significant adverse effects. However, occasional sporadic neurological adverse effects including ADEM can still happen though the incidence of such events is very rare. To conclude, Covid vaccines are reasonably safe with a reported neurological adverse effect of 0.9 for every 100,000 vaccinations. Monitoring of all vaccinated individuals for possible adverse effects, however rare it might be, cannot be overemphasized.

Supporting File
References
  1. National Center for Immunization and Respiratory Diseases (NCIRD), Division of Viral Diseases, Benefits of Getting a COVID-19 Vaccine.Accessed on 01/09/2021.Available at: https://www.cdc.gov/ coronavirus/2019-ncov/vaccines/vaccine-benefits. html/
  2. Lisa Maragakis, M.D, M.P.H, Gabor Kelen, M.D.Is the COVID-19 Vaccine Safe, August 10, 2021, Johns Hopkins Medicine Accessed 01/09/2021 available at: <https://www. hopkinsmedicine.org/health/conditions-anddiseases/coronavirus/is-the-covid19-vaccine-safe/>
  3. Aladdin Y, Shirah B. New-onset refractory status epilepticus following the ChAdOx1 nCoV-19 vaccine. J Neuroimmunol 2021;357:577629.
  4. Lu L, Xiong W, Mu J, et al. The potential neurological effect of the COVID-19 vaccines: A review. Acta Neurol Scand 2021;144(1):3-12.
  5. Huynh W, Cordato DJ, Kehdi E, Masters LT, Dedousis C. Post-vaccination encephalomyelitis: literature review and illustrative case. J Clin Neurosci 2008;15(12):1315-1322.
  6. Miravalle AA, Schreiner T. Neurologic complications of vaccinations. Handb Clin Neurol 2014;121:1549-57.
  7. Bennetto L, Scolding N. Inflammatory/postinfectious encephalomyelitis. J Neurol Neurosurg Psychiatry 2004;75(Suppl.1):i22–i28.
  8. Murthy JM. Acute disseminated encephalomyelitis. Neurol India 2002;50:238–243.
  9. Dodick DW, Silber MH, Noseworthy JH. Acute disseminated encephalomyelitis after accidental injection of a hog vaccine: successful treatment with plasmapheresis. Mayo Clin Proc 1998;73:1193– 1195.
  10. Menge T, Kiesseier BC, Nessler S. Acute disseminated encephalomyelitis: an acute hit against the brain. Curr Opin Neurol 2007;20:247–254. 
  11.  Kawasaki A, Purvin VA, Tang R. Bilateral anterior ischemic optic neuropathy following influenza vaccination. J Neuroophthalmol 1998;18:56–59.
  12. Stuv O, Zamvil SS. Pathogenesis, diagnosis, and treatment of acute disseminated encephalomyelitis. Curr Opin Neurol 1999;12:395–40.
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