Authors: Anıl Kuvandık, Ecenur Özcan, Simay Serin Hülya Sungurtekin Turk J Intensive Care
DOI: 10.4274/tybd.galenos.2021.91885

ABSTRACT

Reports of neurological problems are increasing for the clinical presentation of COVID19. The clinical presentation reported in this study seemed to be a combination of nonspecific complications of the systemic disease, inflammation of the cerebrovascular system, and the effects of a direct viral infection. Creutzfeldt–Jakob disease, a spongiform encephalopathy caused by prions, is characterized by a severe neurological destruction, which has an extremely high mortality. In this publication, we presented a patient who was admitted to the Pamukkale University Anesthesiology Intensive Care Units with the neurological findings that developed after the COVID-19 vaccine (CoronaVac, Sinovac Life Sciences, Beijing, China). The patient died due to he progressive neurological disorders. In cases where rapidly progressive neurological disorders are observed, Creutzfeldt–Jakob disease should be considered and the role of immunity-related conditions in the progression of the disease should be investigated.

Introduction
Neurological effects from COVID-19 infections are now documented in scientific studies.(1) Neurological manifestations may be related such as direct effects of the virus on the nervous system, para-post-infectious immune mediated disease, and neurologic complications of the
systemic effects of COVID-19.(2)Unvaccinated individuals are at higher risk of serious illness
from COVID-19 infection, which can cause temporary or long term neurological effects in some patients. Autoimmunity and the opposing condition, metabolic syndrome, are well known adverse events caused by vaccines.(3) COVID-19infections are related to the induction of auto-antibodies and autoimmune disease which makes it more than reasonable a vaccine can do the same. There is no evidence that theCOVID-19 vaccines lead to neurodegenerative diseases as
far as we know. In this case report, a patient who was diagnosed with Creutzfeldt-Jakob disease (CJD) after Covid-19 vaccine was examined.
Case Report
A 82-year-old female patient with a known diagnosis of hypertension and dementia started to have tremors and weakness on the right side of her body. The patient’s findings emerged one day after the first dose of COVID-19 CoronaVac vaccine was administered. She admitted to the hospital with the addition of symptoms such as regression in her state of consciousness, inability to recognize the people

Discussion
COVID-19 is an unprecedented threat that is straining health system capacities around the world. Neurological symptoms develop in 17.3% to 36.4% of patients in the acute phase of the disease, and 25% of these are caused by central nervous system involvement. Central nervous system involvement is mostly seen as viral meningitis or encephalitis. The most common neurological symptoms are headache, dizziness and changes in consciousness.(4)Possible mechanisms in the neurological involvement of COVID-19; viral encephalitis, systemic inflammation, dysfunction of peripheral organs and cerebrovascular changes. These mechanisms enhance neurological symptoms by aggravating a pre-existing neurological disorder or initiating a new disease.(5) In COVID-19, there is an increase in cytokines and inflammatory mediators resulting from systemic inflammation. Systemic inflammation, on the other hand, supports cognitive decline and neurodegenerative diseases.(6) Authors(7) found prion related sequences in the COVID-19 spike protein which were not found in related coronaviruses. It was also reported a case of prion disease, Creutzfeldt-Jakob disease, initially occurring in a man with COVID-19.(1)Vaccination is an effective strategy to reduce the burden of preventable diseases. However, many clinical studies have revealed that various vaccines may be associated with different neurological disorders and autoimmune pathologies. Although some studies show that neurological disorders that develop after vaccination may not be related to the vaccine, these results may be coincidental.(8) In addition, reporting of post-vaccine-related adverse events may increase the hesitation of the public about vaccination and support vaccination opposition. No article has been found in the literature about the Covid-19 vaccines causing encephalitis. Creutzfeldt-Jakob disease is a very rare, rapidly progressing, contagious neurodegenerative disease with a mortality rate of 100% caused by prion proteins. Although CJD is generally sporadic, it can occur in 10% of cases with familial autosomal dominant inheritance.(9) The neuron losses in the gray matter and the many vacuoles in the central nervous system are responsible for the classic sponge-like appearance of the brain and the emergence of specific clinical symptoms in CJD. This infectious disease with fatal consequences is of particular importance as it can be iatrogenically transmitted to healthcare personnel and other patients.(10)Sporadic CJD usually begins with nonspecific symptoms in older ages. Often there are personality disorders, depression, sleep disorders and weight loss. Behavioral problems and cognitive dysfunction are important symptoms. Brain biopsy is the gold standard in diagnosis. Since surgery is risky and samples cannot be taken from the affected area all the time, brain biopsy can be performed in uncertain diagnoses after all non-invasive diagnostic methods are performed.(11) Checking 14-3-3 protein and tau protein in CSF is important in the diagnosis of sporadic CJD. These proteins are markers of neuronal destruction and their concentration increases in the later stages of the disease. In the absence of clinical signs, the 14-3-3 protein has no value and is not specific for CJD. Real-time quaking-induced conversion (RT-QuIC) test is an examination that detects the abnormal scrapie form of the prion protein (PrPsc) and provides a definitive diagnosis.(12) It was used The Centers for Disease Control and Prevention’s (CDC) criteria for CJD diagnosis in our case.(13) Our patient had neurological symptoms and cognitive dysfunction. CSF examination was positive for 14-3-3 protein. We did not have the opportunity to do the RT-QuIC test. Periodic sharp wave complexes (PSWC) in EEG are found in 2/3 of patients with sporadic CJD and are among the diagnostic criteria.(13) The spikes on the EEG are independent of typical signs of myoclonic seizures and are associated with the fusion of dendritic membranes in neurons. Although PSWCs are initially lateralized, they are seen in bilateral frontal localization in progressive disease.(14) In our case, mixed and slow sharp waves observe in EEG were not lateralized. In MRI, the high intensity signal pattern in T2 / FLAIR sequences is compatible with astrogliosis and hyperintensity in diffusion-weighted imaging with the formation of vacuoles and prion protein in the brain. MRI images correlate with symptoms and clinical findings, but hyperintensity decreases in the later stages of the disease and cortical atrophy may be the only finding. Therefore, in the absence of specific imaging findings, if CJD is considered in the differential diagnosis, attention should be paid to when the clinical findings begin.(15) In our case, cortical diffusion restriction was detected in the left parietal, occipital, temporal lobes, and right occipital lobe on MRI. Hyperintensity was observed in the same regions in FLAIR examination. The onset of acute neurological symptoms after Covid19 vaccination suggested that there might be an adverse effect related to the vaccine. Suppression of immunity after vaccination may have accelerated the emergence of prion disease or the onset of the disease may be coincidental. In order for CJD diagnosis to be associated with the vaccine, the cause-effect relationship between them must be revealed. Therefore, further studies are needed in this area.

References

1. Young MJ, O’Hare M, MatielloM, Schmahmann JD. CreutzfeldtJakob disease in a man with
   COVID-19: SARS-CoV-2-accelerateneurodegeneration? Brain Behav Immun.
   2020;89(January):601–3.
2. Ellul MA, Benjamin L, Singh B, Lant S,Michael BD, Easton A, et al. Neurological
   associations of COVID-19. Lancet Neurol[Internet]. 2020;19(9):767–83. Available
   from: http://dx.doi.org/10.1016/S1474-4422(20)30221-0
3. Classen JB. Review of Vaccine Induced Immune Overload and the Resulting Epidemics of Type 1 Diabetes and Metabolic Syndrome, Emphasis on Explaining the Recent Accelerations in the Risk of Prediabetes and other Immune Mediated Diseases. J Mol
   Genet Med. 2014;02(s1).
4. Correia AO, Feitosa PWG, Moreira JL de S, Nogueira SÁR, Fonseca RB, Nobre
   MEP. Neurological manifestations ofCOVID-19 and other coronaviruses: A systematic review [Internet]. Vol.37, Neurology Psychiatry and Brain Research. Elsevier GmbH; 2020 [cited2021 May 29]. p. 27–32. Available from: /pmc/articles/PMC7261450/
5. Heneka MT, Golenbock D, Latz E,Morgan D, Brown R. Immediate andlong-term consequences of COVID19 infections for the development ofneurological disease. Alzheimer’s ResTher [Internet]. 2020 Jun 4 [cited 2021May 29];12(1). Available from: /pmcarticles/PMC7271826/
6. Widmann CN, Heneka MT. Long-termcerebral consequences of sepsis[Internet]. Vol. 13, The Lancet Neurology.Lancet Publishing Group; 2014 [cited2021 May 29]. p. 630–6. Availablefrom: https://pubmed.ncbi.nlm.nih.gov/24849863/
7. Tetz G, Tetz V. SARS-CoV-2 prion-likedomains in spike proteins enable higher
   affinity to ACE2. 2020 Mar 29 [cited 2021Jun 1]; Available from: www.preprints.org
8. Tian M, Yang J, Li L, Li J, Lei W, Shu X.Vaccine-Associated Neurological AdverseEvents: A Case Report and LiteratureReview. Curr Pharm Des [Internet]. 2019Nov 19 [cited 2021 Apr 28];25(43):4570–
9. Available from: https://pubmed.ncbi.nlm.nih.gov/31742492/
10. Belay ED. Transmissible spongiformencephalopathies in humans [Internet].Vol. 53, AnnuRev Microbiol; 1999 [cited 2021 Apr28]. p. 283–314. Available from: https://
    pubmed.ncbi.nlm.nih.gov/10547693/
11. Öz Atalay F, Tolunay Ş, Özgün G, BekarA, Zarifoğlu M. Creutzfeldt-JakobHastaliği:Dört Olgunun Sunumu veLiteratürün Gözden Geçirilmesi. TurkPatoloji Derg. 2015;31(2):148–52.
12. Manix M, Kalakoti P, Henry M, ThakurJ, Menger R, Guthikonda B, et al.Creutzfeldt-Jakob disease: Updated diagnostic criteria, treatment algorithm,
    and the utility of brain biopsy. NeurosurgFocus. 2015;39(5):1–11.
13. Mahale RR, Javali M, Mehta A,Sharma S, Acharya P, Srinivasa R. Astudy of clinical profile, radiological and electroencephalographic characteristics of suspected creutzfeldt-jakob diseasin a tertiary care centre in south IndiaJ Neurosci Rural Pract [Internet]. 2015
    Jan 1 [cited 2021 Apr 28];6(1):39–50.Available from: https://pubmed.ncbi.nlm.nih.gov/25552850/
14. Diagnostic Criteria | Creutzfeldt-JakobDisease, Classic (CJD) | Prion Disease| CDC [Internet]. Centers for DiseaseControl and Prevention. 2018 [cited 2021May 29]. Available from: https://www.cdc.gov/prions/cjd/diagnostic-criteria.html
15. Wieser HG, Schindler K, Zumsteg D. EEGin Creutzfeldt-Jakob disease [Internet].Vol. 117, Clinical Neurophysiology. ClinNeurophysiol; 2006 [cited 2021 Apr28]. p. 935–51. Available from: https://pubmed.ncbi.nlm.nih.gov/16442343/
16. Na DL, Suh CK, Choi SH, Moon HS, SeoDW, Kim SE, et al. Diffusion-weighted magnetic resonance imaging in probable Creutzfeldt- Jakob disease: A clinical anatomic correlation. Arch Neurol[Internet]. 1999 Aug [cited 2021 Apr28];56(8):951–7. Available from: https://pubmed.ncbi.nlm.nih.gov/104488