Association of seizure with COVID‐19 vaccines in persons with epilepsy: A systematic review and meta‐analysis

Rafati, Ali; Jameie, Melika; Amanollahi, Mobina; Jameie, Mana; Pasebani, Yeganeh; Sakhaei, Delaram; Ilkhani, Saba; Rashedi, Sina; Pasebani, Mohammad Yazdan; Azadi, Mohammadreza; Rahimlou, Mehran; Kwon, Churl‐Su

doi:10.1002/jmv.29118

Cited by 12 publications

(5 citation statements)

References 53 publications

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“…Post-vaccination seizure aggravation (PVSA) was observed in 5.3% of subjects in our cohort, which is consistent with the findings in a previous meta-analysis [ 24 ]. Of note, one subject had a PVSA requiring hospitalization 30 days after the second dose of BNT162b2 vaccination, without status epilepticus or requirement of intensive care.…”

Section: Discussionsupporting

confidence: 93%

Risk of Seizure Aggravation after COVID-19 Vaccinations in Patients with Epilepsy

Leung,

Ho,

Leung

et al. 2024

Vaccines

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Although Coronavirus disease 2019 (COVID-19) vaccinations are generally recommended for persons with epilepsy (PwE), a significant vaccination gap remains due to patient concerns over the risk of post-vaccination seizure aggravation (PVSA). In this single-centre, retrospective cohort study, we aimed to determine the early (7-day) and delayed (30-day) risk of PVSA, and to identify clinical predictors of PVSA among PwE. Adult epilepsy patients aged ≥18 years without a history of COVID-19 infection were recruited from a specialty epilepsy clinic in early 2022. Demographic, epilepsy characteristics, and vaccination data were extracted from a centralized electronic patient record. Seizure frequency before and after vaccination, vaccination-related adverse effects, and reasons for or against vaccination were obtained by a structured questionnaire. A total of 786 PwEs were included, of which 27.0% were drug-resistant. At the time of recruitment, 74.6% had at least 1 dose of the COVID-19 vaccine. Subjects with higher seizure frequency (p < 0.0005), on more anti-seizure medications (p = 0.004), or had drug-resistant epilepsy (p = 0.001) were less likely to be vaccinated. No significant increase in seizure frequency was observed in the early (7 days) and delayed phases (30 days) after vaccination in our cohort. On the contrary, there was an overall significant reduction in seizure frequency 30 days after vaccination (1.31 vs. 1.89, t = 3.436; p = 0.001). This difference was seen in both types of vaccine (BNT162b2 and CoronaVac) and drug-resistant epilepsy, but just missed significance for the second dose (1.13 vs. 1.87, t = 1.921; p = 0.055). Only 5.3% had PVSA after either dose of vaccine. Higher pre-vaccination seizure frequency of ≥1 per week (OR 3.01, 95% CI 1.05–8.62; p = 0.04) and drug-resistant status (OR 3.32, 95% CI 1.45–249 7.61; p = 0.005) were predictive of PVSA. Meanwhile, seizure freedom for 3 months before vaccination was independently associated with a lower risk of PVSA (OR 0.11, 95% CI 0.04–0.28; p < 0.0005). This may guide epilepsy treatment strategies to achieve better seizure control for at least 3 months prior to vaccination. As COVID-19 shifts to an endemic phase, this study provides important data demonstrating the overall safety of COVID-19 vaccinations among PwE. Identification of high-risk patients with subsequent individualized approaches in treatment and monitoring strategies may alleviate vaccination hesitancy among PwE.

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Section: Discussionsupporting

confidence: 93%

Risk of Seizure Aggravation after COVID-19 Vaccinations in Patients with Epilepsy

Leung,

Ho,

Leung

et al. 2024

Vaccines

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“…This has been observed for many other complications and other populations as well. For instance, in persons with epilepsy, the risk of increased seizure frequency after vaccinations seems to be less than that of SARS-CoV-2 infection . Furthermore, some other adverse events were also more pronounced in SARS-CoV-2 infection vs vaccine, such as Bell palsy, Guillain-Barré syndrome, encephalomyelitis, meningitis, and transverse myelitis .…”

Section: Discussionmentioning

confidence: 99%

“…For instance, in persons with epilepsy, the risk of increased seizure frequency after vaccinations seems to be less than that of SARS-CoV-2 infection. 21,47 Furthermore, some other adverse events were also more pronounced in SARS-CoV-2 infection vs vaccine, such as Bell palsy, Guillain-Barré syndrome, encephalomyelitis, meningitis, and transverse myelitis. 14,48 The inflammation after infection or vaccination seems to be responsible for the development of many adverse events.…”

Section: Sars-cov-2 Infection Vs Sars-cov-2 Vaccinesmentioning

confidence: 99%

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Association of New-Onset Seizures With SARS-CoV-2 Vaccines

Rafati,

Jameie,

Amanollahi

et al. 2024

JAMA Neurol

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ImportanceSeizures have been reported as an adverse effect of the SARS-CoV-2 vaccine. However, no study has answered the question of whether there is any association between seizures in the general population and COVID-19 vaccination.ObjectiveTo evaluate the seizure incidence among SARS-CoV-2 vaccine recipients compared with those who received a placebo.Data SourcesA systematic search of MEDLINE (via PubMed), Web of Science, Scopus, Cochrane Library, Google Scholar, review publications, editorials, letters to editors, and conference papers, along with the references of the included studies from December 2019 to July 7, 2023.Study SelectionRandomized clinical trials (RCTs) reporting seizure incidence with SARS-CoV-2 vaccination were included.Data Extraction and SynthesisThis study is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework and used the Mantel-Haenszel method with random- and common-effect models. The risk of bias of the studies was assessed using the Cochrane assessment tool for RCTs.Main Outcomes and MeasuresThe outcome of interest was new-onset seizure incidence proportion compared among (1) SARS-CoV-2 vaccine recipients and (2) placebo recipients.ResultsSix RCTs were included in the study. Results of the pooled analysis comparing the incidence of new-onset seizure between the 63 521 vaccine and 54 919 placebo recipients in the 28-day follow-up after vaccine/placebo injection showed no statistically significant difference between the 2 groups (9 events [0.014%] in vaccine and 1 event [0.002%] in placebo recipients; odds ratio [OR], 2.70; 95% CI, 0.76-9.57; P = .12; I2 = 0%, τ2 = 0, Cochran Q P = .74). Likewise, in the entire blinded-phase period after injection, with a median of more than 43 days, no significant difference was identified between the vaccine and placebo groups regarding incident new-onset seizure (13/43 724 events [0.03%] in vaccine and 5/40 612 [0.012%] in placebo recipients; OR, 2.31; 95% CI, 0.86-3.23, P &gt; .99, I2 = 0%, τ2 = 0, Cochran Q P = .95).Conclusions and RelevanceAccording to this systematic review and meta-analysis, there was no statistically significant difference in the risk of new-onset seizure incidence between vaccinated individuals and placebo recipients.

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“…An increase in inflammatory factors also worsens neuronal necrosis and apoptosis in the central nervous system, particularly in several hippocampal regions. These pro-inflammatory factors are crucial in the development of epilepsy [60,61]. At present, the role of COVID-19 in the occurrence of epilepsy is not clear, and a large number of studies on this are needed.…”

Section: Discussionmentioning

confidence: 99%

Integrating Proteomics and Transcriptomics Reveals the Potential Pathways of Hippocampal Neuron Apoptosis in Dravet Syndrome Model Mice

Kong,

Dai,

Zeng

et al. 2024

IJMS

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An important component contributing to the onset of epilepsy is the death of hippocampal neurons. Several studies have shown that Dravet syndrome model mice: Scn1a KO mice have a high number of apoptotic neurons following seizures, but the precise mechanism underlying this remains unclear. The aim of this research was to elucidate the potential molecular mechanism of neuronal apoptosis in Scn1a KO mice by integrating proteomics and transcriptomics, with the ultimate goal of offering better neuroprotection. We found that apoptotic processes were enriched in both proteomic and transcriptomic GO analyses, and KEGG results also indicated that differential proteins and genes play a role in neurotransmission, the cell cycle, apoptosis, and neuroinflammation. Then, we examined the upstream and downstream KGML interactions of the pathways to determine the relationship between the two omics, and we found that the HIF-1 signaling pathway plays a significant role in the onset and apoptosis of epilepsy. Meanwhile, the expression of the apoptosis-related protein VHL decreased in this pathway, and the expression of p21 was upregulated. Therefore, this study suggests that VHL/HIF-1α/p21 might be involved in the apoptosis of hippocampal neurons in Scn1a KO mice.

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Association of seizure with COVID‐19 vaccines in persons with epilepsy: A systematic review and meta‐analysis

Cited by 12 publications

References 53 publications

Risk of Seizure Aggravation after COVID-19 Vaccinations in Patients with Epilepsy

Risk of Seizure Aggravation after COVID-19 Vaccinations in Patients with Epilepsy

Association of New-Onset Seizures With SARS-CoV-2 Vaccines

Integrating Proteomics and Transcriptomics Reveals the Potential Pathways of Hippocampal Neuron Apoptosis in Dravet Syndrome Model Mice

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