“Vaccine Encephalopathy” – Autism, Epilepsy, & Age of Onset

“Vaccine Encephalopathy”. Despite the medical-sounding terminology, it’s a very poorly defined term and is used to describe developmental regression, seizures, and sometimes coma in an infant or young child, beginning 1-14 days following vaccination. The seizures in particular are defined as “febrile” meaning that they’re often associated with fever. This term tends to be used infrequently in the professional literature and has instead been exapted for use in less scientific contexts.

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Although there has been considerable public scare over particular vaccines (pertussis, MMR, etc.), the literature on “vaccine encephalopathy” overwhelmingly indicates that it is not the vaccination per se that increases risk in susceptible individuals to seizures and regression but an immune reaction and sometimes the association with fever (hence the term “febrile) [1]. Such seizures are also known to occur with infant infections, indicating that it is the immune reaction that appears to be the common factor, not vaccination. Intriguingly, though the instances seem to be rare, different vaccines induce seizures at different time periods, such that pertussis vaccination typically induces febrile seizures within one day following inoculation, meanwhile MMR induces febrile seizures on average 8-14 days following inoculation [2].

The prototypical vaccine encephalopathy is remarkably similar to a form of epilepsy called Dravet Syndrome. In this condition, seizures sometimes present in infancy following fever, which can succeed vaccination or other illness [1]. For those who have already developed epilepsy, seizure incidence can also increase following vaccination [3]. Regression follows around the second year of life, after which other seizure types start to arise. Approximately 1 in 30,000 infants will present with Dravet Syndrome and about 2/3rds of those cases will have mutations in the SCN1A gene, a voltage-gated sodium channel [4, 5]. Approximately 1/4th of children with Dravet Syndrome will also be diagnosed with autism, making it a significant syndromic form of autism. A small but significant portion of people with autism also have SCN1A mutations [6].

A fascinating study by Berkovic et al. (2007) took a look at 14 purported cases of “vaccine encephalopathy” used in a previous study. Through records they confirmed the occurrence of seizure onset within 72 hours of vaccination with pertussis. They then genotyped each of the 14 patients for mutations in the SCN1A gene. They found that 11 of the 14 people indeed had SCN1A mutations, 5 of which lead to probable protein truncation and 6 missense mutations. 9 of the 11 patients also had parental DNA available which was subsequently genotyped, the results of which indicated that all 9 cases were de novo mutations. Ultimately, they found that of the 11 cases, 8 fulfilled diagnosis for Dravet Syndrome (aka, Severe Myoclonic Epilepsy of Infancy, SMEI) and 4 had borderline Dravet’s (SMEB).

Even though the authors acknowledged vaccination as a potential trigger, they nevertheless felt that a change to vaccination protocol with such infants would be useless, indicating that “individuals with such mutations seem to develop [Dravet’s Syndrome] whether or not they are immunised in the first year of life” (p. 491). They admitted, however, that their “experimental design does not address this issue…” (p. 491).

Thankfully, some of the same authors went on to test this hypothesis in a later study, finding that vaccination correlated with an earlier onset of illness [7]. Although the total number of subjects was small (N = 40), the study outcome didn’t indicate a divergence in intellectual outcome, either in terms of regression or intellectual disability, between those in the early age of onset group and those later affected. The authors recanted some of their previous doubts regarding the validity of “vaccine encephalopathy”:

“Although our earlier report suggested that vaccine encephalopathy was not a real disorder, there remains a possibility, because of the apparent temporal association, that DTP vaccination might sometimes trigger the onset of Dravet syndrome. If . . . the observation of the temporal association is valid, a gene–environment interaction might be occurring” (p. 593).

Ultimately, they found that approximately 1/3rd of their Dravet Syndrome patients developed seizures within 72 hours following vaccination, and that disease onset occurred an average of 7.8 weeks earlier than in those who did not develop seizures immediately following inoculation. Nevertheless, the authors conclude that, “there is no rational basis for withholding DTP immunisation for potentially lethal childhood diseases for fear of causing Dravet syndrome or injuring the brain by a direct or presumed immune-mediated mechanism” (p. 597).

While I can appreciate the desire to avoid fearmongering in a culture which is rife with vaccination paranoia, on the other hand, regardless of whether vaccination alters outcome severity, knowingly triggering precocious disease onset seems decidedly unethical. Instead, further detailed study and a more nuanced, informed approach to vaccination schedule in such infants seems warranted, including that of genotyping prior to inoculation. Especially considering the risks of Sudden Infant Death (SID) and mortality due to status epilepticus associated with Dravet Syndrome [ref]. Such revised-vaccination protocols are already in place for infants with certain metabolic disorders.

It has long been postulated that inflammation and even autoimmunity may play roles in susceptibility to epilepsy. The occurrence of fever and infection are documented in some types of seizure onset, and even autoimmune conditions like lupus have increased comorbidity with epilepsy [8]. Some CNS-related autoantibodies have also been noted in epileptic patients, as well as patients with autism [9, 10].

Given the high rate of comorbidity and the overlap in etiology between autism and epilepsy, it causes one to wonder whether vaccinations play a role in age of onset of regressive autism, just as they appear to do in many cases of Dravet Syndrome [10]. In fact, regressive and intellectual disability in autism share tight links with the co-occurrence of epilepsy [11]. However, if regressive autism also shares similar trends with Dravet Syndrome, rates of autism occurrence and severity of symptoms may not ultimately be affected following vaccination, just the timing of onset. Which would explain the results of the many epidemiological studies that have failed to find links between autism risk and vaccination. Should this hold true, it would suggest that, no, parents aren’t necessarily crazy when they see their child drastically regress shortly following vaccination, but nor does it mean that vaccines “cause” autism. As it seems with all of biology, it’s probably far more complicated than that.

However, as a parting gift, I also want to stress to parents that vaccination might also protect against earlier age of autism onset and regression, considering the risks that infection confer in precocious symptom onset as is seen in Dravet Syndrome. Consider if you will a large Danish study published in 2012 by Yun et al. Though they reported that vaccination with the pertussis vaccine conferred a small risk for febrile seizures following 1st and 2nd round inoculations, they also found that inoculation in the larger population was a protective factor against seizures from ages 3-15 months. While we can only hypothesize as to the causes of this finding, if we consider vaccinations’ capacity to prevent infection, it may suggest that vaccines play an even more important role in the prevention of precocious onset of seizures and regressive autism by prevention of those very infections. So while some cases of epilepsy and autism could be triggered earlier by vaccination, vaccination may prevent precocious symptom development in a significantly greater number of cases.

This is why we need more research. We don’t need to panic and forgo vaccinations entirely. We need to demand better research so that we can develop nuanced protocols for individualized medicine. However, just as driving carries with it the risk for car accidents, so too must we accept that vaccinations, no matter how well researched, will also carry a modicum of risk. That is simply a fact of our modern life.

18 responses to ““Vaccine Encephalopathy” – Autism, Epilepsy, & Age of Onset

    • I’ll have to think about this, green, although the idea of inheritance in a non-genetic fashion is certainly appealing. I’ll let it simmer in my brain for awhile. Cheers.

      • Not really talking about inheritance here although there are trans-generational impacts and influences. But this is a direct cause and effect mechanism.

  1. Hi Emily –

    Nice posting. Regarding the curios nature of the Yun et all, or the different, you might find these articles of interest.

    http://www.ncbi.nlm.nih.gov/pubmed/22649499

    http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0015041

    The upshot seems to be that the development of the innate immune response during infancy is not linear and quantitative measures change based on age, classification of insult, and other factors. Some of the cytokines that get produced at different levels are clearly implicated in the generation of fever with similar, but less frequently replicated analysis into production of seizures.

    Of course, the animal models of *non acute*, but still very real changes in the neuroimmune environment are much more frightening to a simple Internet Drone like myself.

    http://www.ncbi.nlm.nih.gov/pubmed/22982535

    I was at a conference once where a presenter noted something along the lines of ‘if thalidomide didn’t cause gross abnormalities, but instead, reduced IQ by five points, it would still probably be prescribed.’ It is *easy* to tell if a child develops seizures, either post vaccination or not;
    detecting less acute symptoms is much more problematic.

    End rant.

    • passionless, that’s some very interesting info there; I’m saving the articles. Given the variation in immune response in infancy, it would seem that, alongside the info I’ve presented in the article, it would suggest more detailed research is needed in these related fields. I’m not exactly certain whether that will be possible in the current climate. To receive funding for such endeavors would probably be daunting. It’s unfortunate that, although there seems to be large amounts of pseudoscience surrounding these topics, what good leads there have been have also gotten sucked in under the pseudoscience label and are subsequently ignored by the professional communities. The unfortunate humanness of science.

  2. 22q11 deletion syndrome shares many findings with Dravet Symdrome. 93% of cases are caused by a de novo gene mutatiom. Both syndromes have multiple CNS and physical anomolies and both syndromes are associated with immune deficiencies, 77% of children with the 22q11 deletion have immune deficiencies. Like Dravot vaccinating with live vaccines is not recommended.

    http://www.ncbi.nlm.nih.gov/books/NBK1523/

    • Ah very interesting, Robert. I’ll make a note of that for future reference. I think one of the genes of interest in that region is TBX1, which affects neural fate determination. Very interesting. This makes me wonder, even moreso, whether a number of types of epilepsy aren’t vulnerable to immune upregulation in the worsening or timing of the phenotype.

  3. Howdy,

    First of all, I want to thank you for writing a balanced piece on autism and vaccines. It isn’t often that someone writes on the subject without going to one extreme or the other.

    Second, in regards to your point about a person eventually developing autism even without the earlier trigger, I think you are spot on with an important caveat. I have three daughters with autism – a set of identical twins and their younger sister – and their history bears out what you are saying.

    The twins both experienced a regression when they were about a year old that was probably caused by a variety of things but the final straw was likely vaccines. The details aren’t really important but the long and short of it is that we gave them several vaccines over a period of time when their immune systems were already extremely stressed and, in retrospect, it seems like it was more than they could take. (I wrote about the details here – http://autismjabberwocky.blogspot.com/2011/01/two-years-of-autism-jabberwocky.html” – if anyone is curious.)

    Now their younger sister did go onto develop autism as well but she never experienced a regression. She did not start showing signs of autism until she was older and even then it took a while for autism to be apparent. It light of the twin’s diagnosis at 18 months, we had her evaluated at two years old and she was still not showing any clear signs of autism. She did not receive a diagnosis until she was closer to three years old.

    All of which brings me, in a rather long winded fashion, to my point. The age that autism develops and whether it is accompanied by a regression seems to make a big difference in severity and outcome. The twin’s regression and decent into autism cost set them back significantly and it literally took them years to regain the ground that they lost during their regression. In comparison, their sister, who never regressed and never lost any skills, is much higher functioning and is not as far behind her peers.

    All three girls are still relatively young so I don’t know yet what their eventual functioning level will be. But I do strongly suspect that the twin’s autism would look more like their sister’s if they had not regressed. So the timing of the trigger that leads to autism might make a big difference in what the outcome is. Or at least it might in my children.

    • Hi, M.J., thanks very much for your personal story. The questions you raise are certainly ones I would raise myself, whether vaccination ultimately effects diagnostic outcome in terms of functioning in autism. Now, truthfully, I was surprised that the Dravet Syndrome studies suggested that functioning– at least in terms of the severity of regression and the development of intellectual disability– was not significantly affected. It was solely the timing of the symptoms that were pushed forward. That, in and of itself, to me is a good reason for readdressing vaccination schedule (not that it HAS to be postponed, but I consider it certainly reason to reconsider the status quo for these kinds of cases and to open up dialogue and weigh the pros and cons). 7.8 more weeks of quality of life is something I would consider very important and I would imagine a great many parents would feel the same.

      So I’m genuinely curious whether autism might follow the trend seen in Dravet Syndrome (which may be reassuring to some people to know that their child would’ve ended up autistic regardless), or whether there are, as you suspect with your own girls’ stories, measurable differences in outcome aside from diagnosis. One can’t say whether your twins would have eventually regressed or not had their vaccine schedule not been what it was, even though you have their sister to compare to. Hopefully, future studies might elucidate a larger trend across populations– if anyone can possibly ever get funding to address these questions, that is. Let’s admit, it’s not a popular topic but has become pretty laughable, if not downright infuriating.

      Do your twins also have epilepsy or have they been checked out for seizures?

      Did their younger sister also receive a similar vaccine schedule or did you have it altered?

      • Emily,

        You are certainly right that it is impossible to know whether the twins would have regressed into autism later or had a more gradual appearance of autism like their sister did without the specific sequence of events that happened. As you said in the main post, I don’t think it was the vaccines themselves that tipped the scales but rather the immune reaction that the vaccines caused that was the final straw. I think we could have at least postponed the regression if we knew then what we know about them now.

        To answer your questions, the twins do not show any signs of epilepsy. We have never seen any signs of seizures (my wife knows what to look for) and an EEG that was done shortly after their regression came up clean. They do not have genetic mutations that are associated with epilepsy. But, from what I understand, epilepsy tends to appear in the teenage years when autism in involved.

        And we did a number of things different with the youngest, including playing with the vaccination schedule. She is fully vaccinated but we spaced out the vaccines so she never got more than one or two at a time and we never gave her one if she showed the slightest sign of being sick. I don’t know whether that made the difference or one of the other things that we did differently made the difference. Most of the other things we did differently were also specifically targeted at things that gave the twins problems so it could have been any one of them that made the difference.

        Or maybe none of them made a difference and she simply has a different mix of whatever it is that makes up her autism and was never going to regress in the first place. None of the girls has any genetic mutation that is linked to autism (or any other developmental disorder) but they do show similar biological disruptions – and in that regard the youngest is closer to “normal” than her sisters are. But without knowing what it is that is “causing” their autism it is impossible to know what made the difference.

  4. @greencentre, I would certainly considerably anything transgenerational a form of inheritance. I’m not into the classic concepts of inheritance by any means. One can even “inherit” the environment, just as one inherits a house. So I’m using the term much more loosely.

  5. M.J., thanks for the reply. Though I am no expert in epilepsy, I believe there are two time periods of vulnerability to seizures in autism. The first tends to be early and can also be much more severe; the second, as you mention, is in adolescence, when hormonal changes seem to somehow tip the balance and push the person over a threshold.

    I find it interesting that your family would be considered multiplex, in that you have 3 daughters with autism, 2 have a regressive form, and 1 has a more typical presentation. It suggests that there’s more of a relationship between regressive and non-regressive forms than one might think. Rather than considering them as distinct autism subtypes, it would suggest, at least within families, it is more of a spectrum even if behaviorally they may differ considerably. Since I’m very interested in attempting to define autism at the molecular, cellular, and structural levels, it’s a good reminder to me to not separate out regressive autism as though it’s something entirely different.

    • Emily,

      Multiplex families are funny things. There seem to be a lot of assumptions about them that, in my limited experience, aren’t exactly true. At least I know that they don’t hold true for my family and some of the other multiplex families that I know. Its sort of link the assumptions that people make about autism in identical twins – it isn’t quite like you would expect.

      When you have multiple children – or identical twins – with autism people automatically assume that there is a strong genetic component to the autism. And yet if you look at my children there is nothing that they share that is known to be linked to autism. Obviously there might be something more subtle or some genetic link that hasn’t been discovered yet, but the state of the art diagnostics from several years ago couldn’t find anything.

      But one very interesting thing that they did find was the twins each had their own distinct CNVs. I’m not a genetics expert by any stretch of the imagination but from what I understand that is not an expected result to see in 5 year old identical twins.

      Another commonly held assumption is that autism in the same family is going to “look” similar. But even the twin’s autism looks different from each other. If you spend a lot of time with them you will see several core bits of their autism that they share but in outward appearance and behaviors they can be quite different. Their younger sister doesn’t even share the same core problems although she does have the fun habit of imitating her sister’s behaviors and stims (actually she will imitate other children with autism as well, it is only the typical children that she doesn’t imitate).

      After you run into things like this in your own family enough times and see similar patterns in other multiplex families it starts to make you wonder.

      The only place my girls do start look alike is in their blood work. They all have certain abnormalities that they all share to a greater or lesser degree. For example, all of them are zinc deficient – even when you give them zinc supplements it is hard to keep their zinc level in the range it needs to be in. Another example is their immune systems – some of the tests are way out of bounds on the high side while others are way out of bounds on the low side.

      All of that is to say that standard assumptions about how multiplex families work might not be true. The saying about if you’ve seen one person with autism, you’ve seen one person with autism also holds true inside multiplex families and even in sets of identical twins. You almost have to throw out any assumption or classification you would make based out outward observable appearance of autism – whether it is regressive vs non-regressive, certain symptoms being there or not there, or even level of functioning – and instead focus on the biological abnormalities and using those to group cases.

      Sorry for being so long winded, I’ll stop rambling now.

      • Do you remember where the CNVs for your girls were located? I mean, were they completely different CNVs or were they located near one another? Just curious since different CNVs can occur from a single unstable region.

      • The CNVs aren’t close to each other – twin A has copy losses at 1q44 and Xp22 while Twin B had a copy loss at 6p25.

        They have been genetically tested to establish that they are identical twins so there is no way the that I can think of that the mutations could have been inherited or in the sperm or egg. Since they don’t share the mutations it seems likely that they were caused by something after they split which would have been within the first few days after conception since they were Di-Di. Either that or some strange form of somatic mosciacism.

        Either way, it seems most likely that something caused the CNVs after conception which is not when CNVs are typically supposed to happen.

        Which make me wonder about the association between rare CNVs and autism. A recent study pointed out that rare CNVs are as much as four times more common in autism (although still only appearing in about 4 percent of autism cases). But do the rare CNVs contribute to the risk of autism, which is the presumption, or does whatever cause the autism increase the risk of CNVs?

  6. M.J., your question is something I’ve wondered myself. A potential example which I often prefer to cite is valproic acid. Not only does it seem to promote autism via targeting gene activity through interference of the epigenome, but there is also the possibility that, by targeting parts of the epigenome, which itself can drive stabilization/destabilization, that DNA mutations may become more likely, especially those directly a result of recombination events.

  7. “Which make me wonder about the association between rare CNVs and autism. A recent study pointed out that rare CNVs are as much as four times more common in autism (although still only appearing in about 4 percent of autism cases). But do the rare CNVs contribute to the risk of autism, which is the presumption, or does whatever cause the autism increase the risk of CNVs?

    Same here! This also brings to mind Balestrieri findings, ie the question of ‘awakening’ of mobile elements (the ones capable of messing up the code) through env insults during embrionic development … Remember that study I posted recently, showing the mutation that caused MR and dev problems was a direct cause of HERV reactivation.

    • It’s not exactly HERV reactivation per se. Long noncoding RNAs (lncRNAs) are important regulators of tissue-specific functions and house, preferentially, ERVs, moreso than other transposable elements. One possibility is that increased ERV transcription may indicate epimutation. Some current research (not yet published) has had preliminary findings of permanently increased ERV production following prenatal insult with an epigenetic teratogen.

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