Impact of COVID-19 vaccination in patients with epilepsy
- Open Access
- 01.12.2024
- Research
Erschienen in:
Abstract
Introduction
In December 2019, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), broke out and led to a rapid worldwide pandemic [1]. By July 2021, more than 3,839 million COVID-19 vaccine doses had been administered globally [2]. Although the vaccine is thought to be safe for most people, patients with some preexisting conditions are still hesitant to accept the vaccine [3].
Epilepsy is one of the most serious neurological disorders, with more than 70 million people worldwide suffering from this disorder. Multiple factors may have fuelled vaccination hesitancy, including safety concerns, lack of trust in the information provided by government and pharmaceutical companies as well as conflicting opinions on social media platforms [4, 5]. For (PWE), one of the most common concerns contributing to vaccination hesitancy has been the potential for seizure exacerbation [6‐8]. Despite the established safety of similar vaccinations in PWE [9]. The aim of this work was to investigate the impact of COVID-19 different vaccines on seizure control in PWE.
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Methods
This observational retrospective study was carried out on patients with epilepsy (PWE) who received at least the first dose of any COVID-19 vaccine. Eligibility criteria included: PWE > 18 years old, who have completed at least 1 month since the date of receiving the first dose. Patients who did not adhere to their antiseizure medications (ASMs) or those with an intellectual disability were excluded from the study, or patients who had a history of similar vaccine-induced seizure exacerbation.
The patients were recruited from two epilepsy clinics, at (blinded for peer review) and (blinded for peer review), from 15-6-2022 to 15-6-2023. Informed written consent was obtained from all enrolled patients. The study received ethical approval from the Neurology Department, Faculty of Medicine (blinded for peer review) on 15-5-2022 with approval number (R 230-94).
The following data were collected from medical records and revised by an expert neurologist: age at onset, seizure type, etiology according to the International League Against Epilepsy (ILAE 2017) classification, and the current used Anti-seizure medications (ASMs).
A questionnaire designed by the authors was administered during a face-to-face interview with each patient, asking about the date of receiving the first dose, the name of the vaccine, and a checklist of the side effects of the COVID-19 vaccine, which included fever, headache, fatigue, dizziness, myalgia, and others. Patients who previously contracted COVID-19 infection were also asked to weigh seizure control during the infection period against the period following vaccination.
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Seizure frequency was documented during the month preceding and the month following the first dose administration. A particular concern was given to the first 24 h immediately after the first dose. In general, vaccine-associated seizures are defined as seizures that occur within 15 days of receiving the vaccine [10]. However, the evaluation period was further extended in the present study to 30 days, and we defined the exacerbation of the seizures by doubling the seizure frequency during the month following vaccine administration compared to the month preceding the vaccination.
COVID-19 vaccines were categorized into either inactivated viral vaccine (Vac Sinovac and Sinopharm BBIBP vaccines), mRNA vaccines (Pfizer, and Moderna), or adenoviral vector-based vaccines (AstraZeneca, Johnson & Johnson and Sputnik V vaccines) [11].
Sample size calculation
The sample size was calculated using Epi info, version 3.5.1, 2008. Based on a lifetime prevalence of epilepsy of 7.60 per 1,000 persons [12], to achieve a 95% confidence level, a total sample size of at least 98 patients was required.
Statistical analysis
The data was coded and entered using the statistical package for Social Science version 25 (SPSS v 25). Normally distributed quantitative data such as age were expressed as mean (SD), while non-normally distributed quantitive data such as age at seizure onset and frequency were expressed as median (IQR). Categorical data, such as sex, seizure etiology and type, ASMs, COVID-19 vaccines, and their adverse effects, and seizure exacerbation following COVID-19 infection and vaccination were expressed as numbers (%). Independent sample t- test was used for comparison between patients who experienced post-COVID-19 vaccine seizure exacerbation and patients who did not experience it regarding age, whereas Mann–Whitne test was used for comparison between patients who experienced post- COVID-19 vaccine seizure exacerbation and patients who did not experience it regarding the age at seizure onset. Wilcoxon test was used for comparison between seizure frequency in the month preceding and the month following COVID-19 vaccination. Chi square test was used for comparison between patients who experienced post-COVID-19 vaccine seizure exacerbation and patients who did not experience it regarding the seizure etiology, COVID-19 vaccine, and seizure exacerbation following COVID-19 infection. P ≤ 0.05 was considered significant.
Results
This observational retrospective study was conducted on 110 PWE (71 males and 39 females) who received at least the first dose of any COVID-19 vaccine. The mean age of the included patients was 36.07 (11.44) years. The median age of onset was 16 (IQR = 11.4–24.25) years. Only 33 (30.0%) patients had genetic etiology, 23 (20.9%) patients had structural brain lesions, and the etiology was unknown in 54 (49.1%) patients. Regarding seizure semiology, 56 (50.9%) patients had focal onset seizures, 53 (48.18%) patients had generalized tonic–clonic seizures (GTCS), 4 (3.6%) patients had absence, and 20 (18.2%) patients had myoclonus (Table 1).
Table 1
Demographics and clinical characteristics of the included patients
Patients (n = 110) | ||
|---|---|---|
Age in years [mean (SD)] | 36.07 (11.44) | |
Age at onset in years [median (IQR)] | 16 (11.4–24.25) | |
Sex [n (%)] | Males | 71 (64.5%) |
Females | 39 (35.5%) | |
Seizure etiology according ILAE classification [n (%)] | Unknown | 54 (49.1%) |
Genetic | 33 (30.0%) | |
Structural | 23 (20.9%) | |
ASMs [n (%)] | Sodium valproate | 62 (56.4%) |
Carbamazepine | 42 (38.2%) | |
Phenytoin | 16 (14.5%) | |
Levetiracetam | 61 (55.5%) | |
Lamotrigine | 12 (10.9%) | |
Topiramate | 2 (1.8%) | |
Oxcarbazepine | 1 (0.9%) | |
Eslicarbazepine | 1 (0.9%) | |
Zonisamide | 2 (1.8%) | |
Lacosamide | 2 (1.8%) | |
Clonazepam | 2 (1.8%) | |
Seizure types [n (%)] | Focal | 56 (50.9%) |
GTCS | 53 (48.18%) | |
Absence | 4 (3.6%) | |
Myoclonus | 20 (18.2%) | |
COVID-19 vaccine [n (%)] | AstraZeneca | 20 (18.2%) |
Johnson & Johnson | 1 (0.9%) | |
Moderna | 4 (3.6%) | |
Pfizer | 20 (18.2%) | |
Sinopharm BBIBP | 50 (45.5%) | |
Vac Sinovac | 14 (12.7%) | |
Sputnik V | 1 (0.9%) | |
General adverse effects from COVID-19 vaccine [n (%)] | None | 61 (55.5%) |
Fever | 29 (26.4%) | |
Fatigue | 18 (16.4%) | |
Headache | 19 (17.3%) | |
Myalgia | 18 (16.4%) | |
Dizziness | 5 (4.5%) | |
As for the prescribed ASMs, 43 (39.1%) patients received monotherapy while 67 (60.9%) were on a polytherapy regimen. Detailed ASMs are displayed in Table 1.
Regarding COVID-19 vaccines, 50 (45.5%) patients received Sinopharm BBIBP, 20 (18.2%) patients received AstraZeneca, 20 (18.2%) patients received Pfizer, 14 (12.7%) patients received Vac Sinovac, 4 (3.6%) patients received Moderna, 1 (0.9%) patient received Johnson & Johnson and 1 (0.9%) patient received Sputnik V.
Sixty-one (55.5%) patients did not develop any side effects from vaccination, 29 (26.4%) patients had a fever, 19 (17.3%) patients had a headache, 18 (16.4%) patients had fatigue, 18 (16.4%) patients had myalgia, and 5 (4.5%) patients had dizziness (Table 1).
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Regarding the impact of COVID-19 infection and vaccination on seizure type and frequency: there was no statistically significant change in seizure frequency following receiving COVID-19 vaccines, either adenoviral vector vaccines (AstraZeneca, Johnson & Johnson, and Sputnik V) inactivated vaccines (Sinopharm BBIBP and Vac Sinovac), or mRNA vaccines (Moderna and Pfizer) (P- = 0.733, 0.778, 1 respectively) (Table 2).
Table 2
Impact of the type of COVID-19 vaccine on seizure frequency
Seizure frequency in the month preceding vaccination [median (IQR)] | Seizure frequency in the month following vaccination [median (IQR)] | P-value | |
|---|---|---|---|
All included patients (n = 110) | 0 (0–0) | 0 (0–1) | 0.675 |
Patients who received adenoviral vector vaccine (n = 22) | 0 (0–1) | 0 (0–1) | 0.733 |
Patients who received inactivated vaccine (n = 64) | 0 (0–0) | 0 (0–1) | 0.778 |
Patients who received mRNA vaccine (n = 24) | 0 (0–0) | 0 (0–0) | 1 |
Only 12 (10.9%) patients experienced seizure exacerbation following COVID-19 vaccination; 4.5% (n = 5) of them experienced GTCS, and 4.58% (n = 5) experienced focal seizures. (Table 3). Seizure occurrence in the first 24 h immediately after the vaccine was reported in only one patient.
Table 3
Impact of COVID-19 infection and vaccination on seizure type and frequency
Patients (n = 110) | ||
|---|---|---|
Seizure exacerbation following COVID-19 vaccine [n (%)] | Yes | 12 (10.9%)* |
No | 98 (89.1%) | |
Seizure exacerbation following COVID-19 infection | Not infected | 2 (1.8%) |
No exacerbation following infection | 96 (87.3%) | |
Exacerbation following infection | 12 (10.9%) | |
There were no statistically significant differences between patients who developed seizure exacerbation following COVID-19 vaccination and those who did not develop regarding age, age at onset, seizure etiology, seizure-freedom before receiving COVID-19 vaccination, pre-vaccine seizure frequency, type of vaccine, or seizure exacerbation following COVID-19 infection (Table 4).
Table 4
Factors affecting seizure exacerbation following COVID-19 vaccination
Patients who experienced post- COVID-19 vaccine seizure exacerbation (n = 12) | Patients who didn’t experience post-COVID-19 vaccine seizure exacerbation (n = 98) | P-value | ||
|---|---|---|---|---|
Age in years [mean (SD)] | 31.25 (11.39) | 36.66 (11.37) | 0.122 | |
Age at onset in years [median (IQR)] | 16 (12–22.5) | 16 (10–250 | 0.920 | |
Seizure etiology [n (%)] | Unknown | 8 (66.7%) | 46 (46.9%) | 0.372 |
Genetic | 3 (25.0%) | 30 (30.6%) | ||
Structural | 1 (8.3%) | 22 (22.4%) | ||
Seizure freedom before receiving COVID-19 vaccine [n (%)] | Yes | 8 (9.2%) | 79 (90.8%) | 0.262 |
No | 4 (17.4%) | 19 (82.6%) | ||
Pre-vaccine seizure frequency [median (IQR)] | 0 (IQR = 0–1) | 0 (IQR = 0–0) | 0.305 | |
COVID-19 vaccine [n (%)] | AstraZeneca | 3 (25.0%) | 17 (17.3%) | 0.061 |
Johnson & Johnson | 0 (0) | 1 (1.0%) | ||
Moderna | 0 (0) | 4 (4.1% | ||
Pfizer | 1 (8.3%) | 19 (19.4%) | ||
Sinopharm BBIBP | 7 (58.3%) | 43 (43.9%) | ||
Vac Sinovac | 0 (0) | 14 (14.3%) | ||
Sputnik V | 1 (8.3%) | 0 (0) | ||
Seizure exacerbation following COVID-19 infection | Not infected | 0 (0) | 2 (2.0%) | 0.837 |
No exacerbation following infection | 11 (91.7%) | 85 (86.7%) | ||
Exacerbation following infection | 1 (8.3%) | 11 (11.2%) | ||
Discussion
The current study confirmed the overall safety of various COVID-19 vaccines in a sample of Egyptian PWE. This study demonstrated seizure exacerbations in 12 PWE (10.9%), which was comparable to the rate reported by the Chinese study (9.3%) [7]. However, the rate is much higher than the rates previously published in Australia (2.5%) and Kuwait (6.1%) [6]. Such variations may be attributed mainly to baseline differences regarding seizure control among the included patients prior to vaccinations.
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The proportion of seizure exacerbation was estimated to be 5% by a meta-analysis conducted by Rafati, Jameie [13]. Moreover, the overall safety of all COVID-19 vaccines was confirmed by the meta-analysis with no statistically significant difference regarding the effect of vaccine type on seizure control, which comes in line with the current results.
Even if the proportion of post-vaccination seizure exacerbation detected in this study was higher than in previous reports, this should not considered as a limitation against getting the vaccine among PWE, as seizure frequency did not significantly increase compared with the baseline state, regardless of the type of COVID-19 vaccine.
On the other hand, the risk of vaccine-associated seizures must be weighed against the risk of COVID-19 infection-related consequences. It was found that COVID-19 infection might promote seizure exacerbation by activating toll-like receptor 4 [14]. Also, COVID-19 may contribute to an increased risk of SUDEP [15], highlighting the importance of vaccination in averting these negative consequences of COVID-19 infection.
Regarding vaccine-related general adverse effects, 44.5% of patients reported minor symptoms after vaccination, while the others (55.5%) did not experience any adverse effects. These rates are comparable to results published in a previous work targeting healthy Egyptian volunteers [16]. Similarly, a study in Germany [8] confirmed the tolerability and safety profile of various COVID-19 vaccines among PWE.
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Taken as a whole, mass vaccinations against COVID-19 infection should be encouraged among adult PWE. Further, awareness campaigns about efficacy in relation to minimal risk of seizure exacerbation must be conducted to expand the vaccine's acceptance among this group. Particularly, Puteikis and Mameniškienė [17] surveyed a group of PWE who had not yet applied for the COVID-19 vaccine. The authors found that intense fear of the possibility of seizure exacerbations following vaccines was the main reason for their vaccine hesitancy.
We had to acknowledge some study limitations that limit the generalizability of the current results. The relatively small sample size was the most critical one. Also, most PWE received the inactivated type of vaccine. So, extended larger studies are needed to account for the delayed effect of different COVID-19 vaccines on seizure frequency.
Conclusions
There is a low likelihood of COVID-19 vaccine-related seizure exacerbations in PWE. This data can be utilized to counsel PWE regarding the safety of COVID-19 vaccination.
Acknowledgements
The authors acknowledge subjects for their participation and cooperation in this study.
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Declarations
Ethics approval and consent to participate
An informed written consent was taken from each patient. All data obtained from every patient were confidential and were not used outside the study. The patients have rights to withdraw from the study at any time without giving any reason. All the cost of the investigations was afforded by the researcher. The study received ethical approval from the Neurology Department, Faculty of Medicine, EL Fayoum University on 15-5-2022 with approval number (R 230-94).
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
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