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Reports of neurological problems are increasing for the clinical presentation of coronavirus disease-2019 (COVID-19). 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 the 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.
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CASE REPORT / OLGU SUNUMU
©Copyright 2022 by Turkish Society of Intensive Care
Turkish Journal of Intensive Care published by Galenos
Publishing House.
61
Turk J Intensive Care 2022;20:61-64
ÖZ
Koronavirüs hastalığı-2019 (COVID-19) hastalığının klinik seyrinde gelişen nörolojik problemlerle
ilgili raporlar artmaktadır. Bu klinik tablo, sistemik hastalığın spesifik olmayan komplikasyonları,
serebrovasküler sistem iltihabı veya doğrudan viral enfeksiyonun etkilerinin bir kombinasyonu gibi
görünmektedir. Prionların neden olduğu süngerimsi bir ensefalopati olan Creutzfeldt-Jakob hastalığı,
şiddetli nörolojik yıkım ile karakterizedir ve son derece yüksek bir ölüm oranına sahiptir. Bu yayında,
Pamukkale Üniversitesi Anesteziyoloji Yoğun Bakım Ünitesi’ne COVID-19 aşısı (CoronaVac, Sinovac
Life Sciences, Beijing, China) sonrası gelişen nörolojik bulgularla başvuran bir hastayı sunduk. Hasta
ilerleyici nörolojik bozukluklar nedeniyle öldü. Hızla ilerleyen nörolojik bozuklukların görüldüğü
durumlarda Creutzfeldt-Jakob hastalığı düşünülmeli ve bağışıklıkla ilgili durumların hastalığın
ilerlemesindeki rolü araştırılmalıdır.
Anahtar Kelimeler:
COVID-19, aşı, Creutzfeldt-Jakob hastalığı, prion proteini
ABSTRACT
Reports of neurological problems are increasing for the clinical presentation of
coronavirus disease-2019 (COVID-19). 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 the 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.
Keywords:
COVID-19, vaccine, Creutzfeldt-Jakob disease, prion protein
E-mail : anilkuvandik@gmail.com
Phone : +90 544 636 99 32
ORCID ID : orcid.org/0000-0002-7555-6076
Anıl Kuvandık Ph.D. (),
Pamukkale University Faculty of Medicine,
Department of Anesthesiology and Reanimation,
Denizli, Turkey
Anıl Kuvandık, Ecenur Özcan, Simay Karaduman,
Hülya Sungurtekin
Pamukkale University Faculty of Medicine,
Department of Anesthesiology and Reanimation,
Denizli, Turkey
Received/Geliş Tarihi : 12.10 .2021
Accepted/Kabul Tarihi : 21 .12.202 1
Anıl Kuvandık,
Ecenur Özcan,
Simay Karaduman,
Hülya Sungurtekin
Koronavirüs Hastalığı-2019 Aşısı Sonrası
Creutzfeldt-Jakob Hastalığı
Creutzfeldt-Jakob Disease After the Coronavirus
Disease-2019 Vaccination
DOI: 10.4274/tybd.galenos.2021.91885
Introduction
Neurological effects from coronavirus disease-2019
(COVID-19) infections are now documented in scientic
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-19 infections are related to the
induction of autoantibodies and autoimmune disease which
makes it more than reasonable a vaccine can do the same.
There is no evidence that the COVID-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 patiet with a known diagnosis of
hypertension and dementia started to have tremors and
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Turk J Intensive Care 2022;20:61-64
Kuvandık et al. Prion Disease After COVID-19 Vaccination
weakness on the right side of her body. The patient’s
ndings emerged one day after the rst 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
around her, impaired vision, impaired place-time orientation
and meaningless shouts at the following month. She was
admitted to our neurology unit hospital with a diagnosis of
encephalitis and subdural hematoma.
On admission, she has myoclonic contractions
and disorientation in her right extremities. She has no
ndings in cranial nerve examinations. Clonus, rigidity and
hyperreexia were present in the right half of the body.
Glasgow coma scale (GCS) was 10/15 on neurological
examination. Laboratory studies such as liver and kidney
function tests, electrolytes, complete blood count, blood
gas analysis, coagulation tests, thyroid function tests,
autoimmune markers, viral encephalitis markers were done.
Cerebrospinal uid (CSF) samples were taken and examined.
Electroencephalograghy (EEG) examination was performed.
Blood, urine, respiratory secretions and CSF cultures were
made. No abnormal laboratory nding was found in blood
tests. Autoimmune encephalopathy panels were negative.
EEG showed paroxysmal mixed sharp and sharply slow
paroxysms, diffuse slowing of cerebral bioelectrical activity
without lateralization and localization. She received pulse
steroid and intravenous immunoglobulin G (IVIG) therapy
with a diagnosis of autoimmune encephalitis in the
neurology service. When GCS dropped to 4 in the neurology
service, she was intubated and hospitalized in our intensive
care unit. Brain and thorax computed tomography and
cranial magnetic resonance imaging (MRI) examinations
were performed. She received empirical antibiotics and
antiepileptic therapy for meningitis prophylaxis in addition
to pulse steroid and intravenous IVIG therapy in the
intensive care unit. Transesophageal echocardiography was
performed for infective endocarditis. Diffusion-weighted
MRI revealed cortical diffusion restriction in the left parietal,
occipital, temporal lobes and the right occipital lobe. In the
uid-attenuated inversion recovery (FLAIR) examination,
hyperintensity was observed in the same regions (Figure 1).
The patient was diagnosed with sporadic CJD after the
14-3-3 protein test was positive, MRI ndings, physical
examination, and evaluation of the clinical history. As a
result of her examinations, viral encephalitis, autoimmune
encephalitis and subdural hematoma were excluded. The
patient died as a result of the progressive course of the
disease. For the presentation of the patient, the patient was
allowed their relatives.
Figure 1. Brain magnetic resonance imaging (MRI) findings in this case. A,B,C,D: Diffusion-weighted MRI shows cortical diffusion restriction in the left
parietal, occipital, temporal lobes and the right occipital lobe. E,F,G,H: FLAIR examination shows hyperintensity in the same regions
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Turk J Intensive Care 2022;20:61-64
Kuvandık et al. Prion Disease After COVID-19 Vaccination
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 inammation,
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 inammation. Systemic inammation, 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,
CJD, 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.
CJD 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 specic 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 nonspecic 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 specic 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 denitive diagnosis (12). It was used
The Centers for Disease Control and Prevention’s 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 observed
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
ndings, but hyperintensity decreases in the later stages
of the disease and cortical atrophy may be the only nding.
Therefore, in the absence of specic imaging ndings, if CJD
is considered in the differential diagnosis, attention should
be paid to when the clinical ndings 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 COVID-
19 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
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Turk J Intensive Care 2022;20:61-64
Kuvandık et al. Prion Disease After COVID-19 Vaccination
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.
Ethics
Informed Consent: For the presentation of the patient, the
patient was allowed their relatives.
Peer-review: Externally peer-reviewed.
Authorship Contributions
Surgical and Medical Practices: A.K., E.Ö., S.K., H.S.,
Concept: A.K., Design: A.K., Data Collection and/or
Processing: A.K., E.Ö., Analysis and/or Interpretation: A.K.,
E.Ö., S.K., H.S., Literature Search: A.K., E.Ö., Writing: A.K.,
E.Ö.
Conict of Interest: No conict of interest was declared by
the authors.
Financial Disclosure: The authors declared that this study
received no nancial support.
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... The connection with neurodegenerative disease is the ability of the spike protein to interact with heparin-binding, amyloid-forming proteins [192]. Though speculative, these considerations are supported by a case report of prion disease due to vaccination [193]. In an in vitro experiment, spike protein was proteolyzed into smaller segments by neutrophil elastase, some of which exhibited amyloidogenic properties [185]. ...
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Background The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is of a scale not seen since the 1918 influenza pandemic. Although the predominant clinical presentation is with respiratory disease, neurological manifestations are being recognised increasingly. On the basis of knowledge of other coronaviruses, especially those that caused the severe acute respiratory syndrome and Middle East respiratory syndrome epidemics, cases of CNS and peripheral nervous system disease caused by SARS-CoV-2 might be expected to be rare. Recent developments A growing number of case reports and series describe a wide array of neurological manifestations in 901 patients, but many have insufficient detail, reflecting the challenge of studying such patients. Encephalopathy has been reported for 93 patients in total, including 16 (7%) of 214 hospitalised patients with COVID-19 in Wuhan, China, and 40 (69%) of 58 patients in intensive care with COVID-19 in France. Encephalitis has been described in eight patients to date, and Guillain-Barré syndrome in 19 patients. SARS-CoV-2 has been detected in the CSF of some patients. Anosmia and ageusia are common, and can occur in the absence of other clinical features. Unexpectedly, acute cerebrovascular disease is also emerging as an important complication, with cohort studies reporting stroke in 2–6% of patients hospitalised with COVID-19. So far, 96 patients with stroke have been described, who frequently had vascular events in the context of a pro-inflammatory hypercoagulable state with elevated C-reactive protein, D-dimer, and ferritin. Where next? Careful clinical, diagnostic, and epidemiological studies are needed to help define the manifestations and burden of neurological disease caused by SARS-CoV-2. Precise case definitions must be used to distinguish non-specific complications of severe disease (eg, hypoxic encephalopathy and critical care neuropathy) from those caused directly or indirectly by the virus, including infectious, para-infectious, and post-infectious encephalitis, hypercoagulable states leading to stroke, and acute neuropathies such as Guillain-Barré syndrome. Recognition of neurological disease associated with SARS-CoV-2 in patients whose respiratory infection is mild or asymptomatic might prove challenging, especially if the primary COVID-19 illness occurred weeks earlier. The proportion of infections leading to neurological disease will probably remain small. However, these patients might be left with severe neurological sequelae. With so many people infected, the overall number of neurological patients, and their associated health burden and social and economic costs might be large. Health-care planners and policy makers must prepare for this eventuality, while the many ongoing studies investigating neurological associations increase our knowledge base.
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Objective To describe the main neurological manifestations related to coronavirus infection in humans. Methodology A systematic review was conducted regarding clinical studies on cases that had neurological manifestations associated with COVID-19 and other coronaviruses. The search was carried out in the electronic databases PubMed, Scopus, Embase, and LILACS with the following keywords: “coronavirus” or “Sars-CoV-2” or “COVID-19” and “neurologic manifestations” or “neurological symptoms” or “meningitis” or “encephalitis” or “encephalopathy,” following the Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results Seven studies were included. Neurological alterations after CoV infection may vary from 17.3% to 36.4% and, in the pediatric age range, encephalitis may be as frequent as respiratory disorders, affecting 11% and 12% of patients, respectively. The Investigation included 409 patients diagnosed with CoV infection who presented neurological symptoms, with median age range varying from 3 to 62 years. The main neurological alterations were headache (69; 16.8%), dizziness (57, 13.9%), altered consciousness (46; 11.2%), vomiting (26; 6.3%), epileptic crises (7; 1.7%), neuralgia (5; 1.2%), and ataxia (3; 0.7%). The main presumed diagnoses were acute viral meningitis/encephalitis in 25 (6.1%) patients, hypoxic encephalopathy in 23 (5.6%) patients, acute cerebrovascular disease in 6 (1.4%) patients, 1 (0.2%) patient with possible acute disseminated encephalomyelitis, 1 (0.2%) patient with acute necrotizing hemorrhagic encephalopathy, and 2 (1.4%) patients with CoV related to Guillain-Barré syndrome. Conclusion Coronaviruses have important neurotropic potential and they cause neurological alterations that range from mild to severe. The main neurological manifestations found were headache, dizziness and altered consciousness.
Article
Vaccination is an effective strategy to reduce the burden of preventable illness. However, many clinical reports revealed that various vaccinations may associate with neurological disorders, mainly including autoimmune disease, febrile seizure, and vaccine associated paralytic poliomyelitis (VAPP). Although more and more reports revealed that part of above post-vaccine neurological disorders are not directly related to vaccination, it may be merely coincidence. However, these reports may increase the hesitancy on vaccination for public population and influence the coverage of vaccination. In this report, we described a child with acute flaccid paralysis may be caused by poliovirus vaccine. To provide the feasible ways to realize or reduce the risk of neurological adverse events caused by vaccines, we further provide a mini review of literatures of vaccination associated neurological adverse events. This revealed that oral poliomyelitis vaccine use exclusively and type 2 serotype poliomyelitis vaccine virus were the risk factor of VAPP. Combination vaccine was associated with an increased risk of ADEM and FS following immunization, when compared with administration of vaccines separately. Even though cases have been reported that vaccination may be trigger of anti-NMDARe and GBS, no direct evidences to prove that vaccination increased the risk of GBS and anti-NMDARe.
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Sepsis is a potentially fatal whole-body inflammatory state caused by severe infection, in which a maladaptive, system-wide inflammatory response follows initial attempts to eliminate pathogens, leading to a dangerous and often fatal increase in the permeability of the blood—brain barrier. These changes in the blood—brain barrier might lead to a major symptom of sepsis, sepsis-associated encephalopathy, which manifests as confusion with a rapid decline in cognitive functions, especially memory, or coma. Once presumed to be entirely reversible, research suggests that sepsis-associated encephalopathy could lead to permanent neurocognitive dysfunction and functional impairments, even after the patient has recovered. Sepsis might act as a major inflammatory hit and potentially increase the brain's susceptibility to neurodegenerative disease, further deterioration of cognitive ability, and risk of developing dementia in later life. Key opportunities for neuroprotective interventions and after-care for people who have survived sepsis might be lost because the long-term neurocognitive and functional consequences of sepsis are not fully characterised.
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Creutzfeldt-Jakob disease is a very rare, progressive neurodegenerative disorder that is incurable and always fatal. It is one of the transmissible spongiform encephalopathies caused by prions. Multiple vacuoles in neuropil and neuronal loss in the gray matter gives the classical sponge-like appearance of brain and are responsible for the typical clinical symptoms. In this report, we present 4 cases referred to the neurology department of Uludağ University with neurological symptoms. Patients were evaluated with electroencephalogram and magnetic resonance imaging, and performed brain biopsies for further investigation. For definitive diagnosis of Creutzfeldt-Jakob disease, accumulation of prion protein in brain was detected immunohistochemically. Patients died within weeks in consequence of rapid progression of the disease. Although Creutzfeldt-Jakob disease is an infrequent disorder, when a patient presents with characteristic clinical symptoms such as rapidly progressive dementia with myoclonus, the diagnosis of Creutzfeldt-Jakob disease should be taken into consideration.