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Advanced Neurology Neurological adverse events post-vaccination

pertussis (DTP), measles, and measles, mumps and type 2, alpha Na 1.2 (SCN2A), 31,32 and katanin catalytic
9
8,9
V
rubella (MMR) vaccines. Neurological AEs following subunit A1 like 2 (KATNAL2). 33
8
vaccinations 10-12 and COVID-19 immunization have also Multiple diseases with a genetic component have
been reviewed. 13-16
been found to be triggered by vaccinations, and
Vaccine excipients have been considered in the several pathological events and diseases, such as the
context of possible associations with neurological AEs. overrepresentation of HLA-DR2 antigen in multiple
In a precautionary measure to decrease overall exposure sclerosis following vaccination (overviewed by Pordeus
34
to mercury in young children, the United States Food et al. ), Dravet syndrome with SCN1A and multiple
35
4,36
and Drug Administration (FDA) removed thimerosal autoimmune diseases have been reported. Children
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from all childhood vaccines in 2001 with the exception of with Dravet syndrome, also known as severe myoclonic
inactivated influenza vaccine in multi-dose vials. A meta- epilepsy of infancy, present with their first seizure following
analysis concluded that exposure to thimerosal-containing vaccination. Mutations in the sodium channel protein
vaccines is associated with AEs, including autism spectrum type 1 subunit alpha (SCN1A) gene are frequently found
disorder (ASD) and speech disorders. A retrospective in these children. Furthermore, 18 additional genes
17
4,36
study of VAERS data from 1998 through 2000 found that associated with neurological AEs have been identified by
the vaccines for hepatitis B (HepB), diphtheria, tetanus sequencing post-vaccination. 38
toxoids, and acellular pertussis (DTaP/DTAP) which Both febrile and afebrile seizures that occur within
contained thimerosal were associated with an increased 14 days after immunization are regarded as vaccine-
risk ratio for the incidence of ASD. It is important to proximate seizures. The vaccine-proximate seizure
18
39
note that VAERS data represents only a small fraction of risk interval (days after vaccination) has been observed
19
AEs experienced by vaccinees due to well-known under to be 5 – 14 days for live-attenuated MMR and measles,
reporting. 20
mumps, rubella, and varicella vaccines and 0 – 2 days for
39
40
Wakefield et al. published a small case series in the three inactivated vaccines. Duffy et al. observed that
Lancet in 1998, indicating a possible association of ASD the risk for febrile seizures increased with concomitant
with the triple MMR vaccination, but this article was administration of influenza trivalent (IIV3) vaccine
retracted in 2010. It should be noted that thimerosal with either pneumococcal (PCV) or DTAP and further
21
is not found in the MMR vaccine. In a retrospective increased with concomitant administration of IIV3,
study in Denmark, 263 of 440,655 vaccinated children PCV, and DTAP. In a Danish study of children aged 15
(normalized frequency = 59.7) developed ASD while – 17 months, the cumulative incidence rate for febrile
1
53 of 96,658 unvaccinated children (normalized seizures per 1,000 children was 2.46 for MMR-vaccinated
41
frequency = 54.8) developed ASD. A time trend analysis children and 0.90 for unvaccinated children. Comparable
22
observed increasing risks of ASD from 1988 to 1993 results to the Danish study were observed in a systematic
while the MMR vaccination rate remained consistent at review and meta-analysis. 42 Feb rile seizures attributed to
over 95% for boys aged 2 to 5 in the United Kingdom. A DTP and MMR vaccines has been estimated to be 6 to 9
23
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similar retrospective time trend analysis from California, and 25 – 34/100,000 children, respectively. A small subset
U.S.A., also showed increasing rates of ASD that were not of these events and all other AEs are passively collected in
associated with MMR vaccination. Based on multiple the VAERS database. 19
24
studies including, 22-25 the current medical community The VAERS database is designed to collect voluntary
consensus does not associate ASD onset with MMR submissions of AEs and SAEs post-immunization. Ideally,
immunization. In addition to exposure-associated AEs, the subset of AEs reported in VAERS is representative of
individual genetics plays a role in ASD. A large number AEs experienced by all vaccinees. As the time between
of genetic variants (copy number variations, duplications, the onset of symptoms of AEs post-immunization
deletions, translocations, inversions, and mutations) increases, the likelihood of reporting decreases, this
are associated with ASD, 26-29 including mutations in the is referred to as reporting bias. Within a population,
genes chromodomain helicase DNA binding protein AEs can occur randomly and these are referred to as
8 (CHD8), neuronal voltage-gated sodium channel, background events. Each vaccine dose represents a single
30
immunization event. AEs reported post-immunization
1 Normalized frequency was calculated by dividing the total number were compared against control populations (who
of AEs by the number of vaccinated individuals and multiplying
by 100,000 to obtain the rate of AE occurrence per 100,000 people received no immunization) for a window of time (days).
vaccinated. Signals that are temporally associated with immunization

Volume 3 Issue 1 (2024) 2 https://doi.org/10.36922/an.2258