Intracranial aneurysm rupture within three days after receiving mRNA anti-COVID-19 vaccination: Three case reports
- Department of Neurosurgery, Iwate Prefectural Ofunato Hospital, Ofunato,
- Department of Neurosurgery, Iwate Prefectural Chubu Hospital, Kitakami,
- Department of Neurosurgery, Iwate Medical University, Yahaba, Iwate, Japan.
Sotaro Oshida, Department of Neurosurgery, Iwate Prefectural Ofunato Hospital, Ofunato, Iwate, Japan.
DOI:10.25259/SNI_1144_2021Copyright: © 2022 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
How to cite this article: Sotaro Oshida1, Yosuke Akamatsu2, Yoshiyasu Matsumoto1, Taro Suzuki1, Takuto Sasaki1, Yuki Kondo1, Shunrou Fujiwara3, Hiroshi Kashimura2, Yoshitaka Kubo3, Kuniaki Ogasawara3. Intracranial aneurysm rupture within three days after receiving mRNA anti-COVID-19 vaccination: Three case reports. 31-Mar-2022;13:117
How to cite this URL: Sotaro Oshida1, Yosuke Akamatsu2, Yoshiyasu Matsumoto1, Taro Suzuki1, Takuto Sasaki1, Yuki Kondo1, Shunrou Fujiwara3, Hiroshi Kashimura2, Yoshitaka Kubo3, Kuniaki Ogasawara3. Intracranial aneurysm rupture within three days after receiving mRNA anti-COVID-19 vaccination: Three case reports. 31-Mar-2022;13:117. Available from: https://surgicalneurologyint.com/?post_type=surgicalint_articles&p=11501
Background: Although neurological adverse events have been reported after receiving coronavirus disease 2019 (COVID-19) vaccines, associations between COVID-19 vaccination and aneurysmal subarachnoid hemorrhage (SAH) have rarely been discussed. We report here the incidence and details of three patients who presented with intracranial aneurysm rupture shortly after receiving messenger ribonucleic acid (mRNA) COVID-19 vaccines.
Case Description: We retrospectively reviewed the medical records of individuals who received a first and/ or second dose of mRNA COVID-19 vaccine between March 6, 2021, and June 14, 2021, in a rural district in Japan, and identified the occurrences of aneurysmal SAH within 3 days after mRNA vaccination. We assessed incidence rates (IRs) for aneurysmal SAH within 3 days after vaccination and spontaneous SAH for March 6–June 14, 2021, and for the March 6–June 14 intervals of a 5-year reference period of 2013–2017. We assessed the incidence rate ratio (IRR) of aneurysmal SAH within 3 days after vaccination and spontaneous SAH compared to the crude incidence in the reference period (2013–2017). Among 34,475 individuals vaccinated during the study period, three women presented with aneurysmal SAH (IR: 1058.7/100,000 person-years), compared with 83 SAHs during the reference period (IR: 20.7/100,000 persons-years). IRR was 0.026 (95% confidence interval [CI] 0.0087–0.12; P P = 0.204). All three cases developed SAH within 3 days (range, 0–3 days) of the first or second dose of BNT162b2 mRNA COVID-19 vaccine by Pfizer/BioNTech. The median age at the time of SAH onset was 63.7 years (range, 44– 75 years). Observed locations of ruptured aneurysms in patients were the bifurcations of the middle cerebral artery, internal carotid-posterior communicating artery, and anterior communicating artery, respectively. Favorable outcomes (modified Rankin scale scores, 0–2) were obtained following microsurgical clipping or intra-aneurysm coiling.
Conclusion: Although the advantages of COVID-19 vaccination appear to outweigh the risks, pharmacovigilance must be maintained to monitor potentially fatal adverse events and identify possible associations.
Keywords: Adverse events, mRNA COVID-19 vaccine, Ruptured aneurysm, Subarachnoid hemorrhage
Since late 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly and infected millions worldwide. The intensity and rapidity of SARS-CoV-2 transmission have led to substantial morbidity and mortality, putting considerable pressure on public health systems. Japan started administering vaccines to healthcare workers on February 17, 2021, and subsequently began a campaign of broad inoculation of the general public to ameliorate the effects of the pandemic.[
The Ministry of Health, Labour, and Welfare (MHLW) in Japan reported that t, as of May 7, 2021, a total of 39 people had died after receiving COVID-19 vaccinations.[
A previous systematic review[
We retrospectively reviewed the electronic medical records of all individuals who received a first and/or second dose of BNT162b2 mRNA COVID-19 vaccine between March 6, 2021 and June 14, 2021 (COVID-19 pandemic, 100 days), in the Kenou area (Kitakami City, Hanamaki City, Tono City, and Nishiwaga Town) and Kesen area (Ofunato City, Rikuzentakata City, and Sumita Town), both of which are rural districts in Iwate Prefecture, Japan. The reason for enrolling cases from March 6, 2021, was that vaccination in these rural areas began on this date. From among, these individuals, those presenting with SAH within 3 days after vaccination when side effects of mRNA vaccination appeared to be persistent were included,[
IRs are reported per 100,000 person-years [
Among 34,475 individuals vaccinated between March 6, 2021, and June 14, 2021, three cases presented with intracranial aneurysm rupture in the 3 days after vaccination. The IR of spontaneous SAH calculated using the person-year method with an observation period of 3 days following COVID-19 vaccination was 1058.7 per 100,000 person-years. All three individuals were women, with a median age of 63.7 years (range, 44–75 years). Two patients had histories of hypertension and dyslipidemia, while the other had no history of illness. The median interval from vaccination to onset of SAH was 2 days (range, 0–3 days). Preoperative WFNS grade was I or II in all cases. Saccular aneurysms were diagnosed using three-dimensional CT angiography or DSA in all cases. The aneurysms arose at the bifurcation of the middle cerebral artery (MCA), internal carotid-posterior communicating artery (IC-Pcom), or anterior communicating artery (Acom) in one case each. Microsurgical neck clipping was performed in two of the studied patients and aneurysmal rupture was confirmed intraoperatively. Endovascular coiling was performed in the remaining patient. Clinical outcomes at last follow-up were favorable (mRS score, 0 or 2), after a median follow-up of 57.7 days (range, 24–102 days). The demographic characteristics, clinical features, laboratory data, neuroimaging findings, and treatment course for the three patients are summarized in [
On the other hand, a total of 85 cases of ruptured aneurysms were encountered in these study areas during the same period of March 6–June 14 during the 5 years reference period before the COVID-19 pandemic (2013–2017).[
A 44-year-old woman who had no medical history presented with severe headache 4 h after receiving the second dose of the BNT162b2 mRNA COVID-19 vaccine. On admission, she was unconscious (Glasgow coma scale [GCS] 4). Initial CT of the head revealed diffuse SAH in the basal cistern, thin subdural hematoma, intracranial hematoma (blood volume, 34.3 ml; 33 mm × 52 mm × 40 mm), and communicating hydrocephalus [
Computed tomography (CT) shows subarachnoid hemorrhage (upper, left) and left Sylvian hematoma (upper, right). Preoperative CT angiography demonstrates a saccular aneurysm (white arrow) (lower, left). Intraoperative images of post clip ligation indicating rupture of the aneurysm (white arrow) (lower, right).
A 72-year-old woman with arterial hypertension and dyslipidemia presented with severe headache 3 days after receiving the first dose of BNT162b2 mRNA COVID-19 vaccine. She was fully alert (GCS score 15) on arrival at the emergency department. Initial CT of the head revealed thin SAH in the basal cistern (Fisher II) [
Computed tomography demonstrates subarachnoid hemorrhage (upper). Oblique view of the left carotid injection shows internal carotid-posterior communicating artery aneurysm with a daughter sac (white arrow) (lower, left). Postoperative angiography reveals complete obliteration of the aneurysm (white arrow) (lower, right).
A 75-year-old woman with arterial hypertension and dyslipidemia presented with severe headache 3 days after receiving a first dose of BNT162b2 mRNA COVID-19 vaccine. She was fully alert (GCS score 15) on admission. Initial cranial CT revealed thin SAH in the interhemispheric cistern (Fisher II) [
Computed tomography (CT) (upper, left) and magnetic resonance imaging (upper, right) demonstrate subarachnoid hemorrhage (white and black arrows). Aneurysms were confirmed by CT angiography (white and black arrowhead) (lower, left) and were confirmed as the bleeding source intraoperatively (white arrow) (lower, right).
We have reported here three cases of intracranial aneurysm rupture shortly after receiving the BNT162b2 mRNA COVID-19 vaccine. Three patients developed aneurysmal SAH within 3 days following vaccination in our district. Although the sample size of the present preliminary data was limited, the IR for aneurysmal SAH calculated using the person-year method with an observation period of 3 days following COVID-19 vaccination was 1058.7/100,000 person-years. On the other hand, the IR for spontaneous SAH calculated using the person-year method from 2013 to 2017 was 20.7/100,000 person-years. This IR for Iwate corresponded with an IR of 20.25/100,000 person-year in Japan.[
The mRNA contained in the Pfizer-BioNTech vaccine is translated into the viral spike protein, eliciting antibody production.[
As a limitation of this study, attention should be paid to interpret the statistical results with deeply considering the limited period, region, and number of patients. Further studies as a require to confirm the findings of the present study.
We have reported the cases of three women with intracranial aneurysm rupture shortly after undergoing BNT162b2 mRNA COVID-19 vaccination. Although we believe that the advantages of COVID-19 vaccination outweigh the risks, continuous pharmacovigilance is necessary to monitor for potentially fatal adverse events and identify any possible associations.
The authors certify that they have obtained all appropriate patient consent.
There are no conflicts of interest.
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