My question: should I get the flu shot now?

Again, IANAD, but from what Dr Novella has said, transient nervous-system-like reactions are not unheard of. Serious and long term reactons are very rare and worrying about very rare events usually does more harm than good.

But listen to what your neurologist tells you, not what random anonomous people say over the internet

Thanks so much for your insight.

Still brings me back to a thought I had- Do you think it could be a coincidence that the symptoms began the evening I received the H1N1 shot (11/8), but that it was in fact the seasonal vaccine (10/5) that triggered the issue?

I am still experiencing the tingling (radiates sporadically though body), light spasm/muscle cramping (calf, axilla, feet) and just feel “off”. I am going back to the neurologist tomorrow.

Is there anything specific you (or anyone participating in the is blog) would recommend they look for/test for at this point?

I suspect that some of this is because doing this kind of research is pretty difficult. Mice and rats have different skin thickness than do humans, so doing vaccine comparisons by delivery mechanism (needle vs Pharmajet) is tricky and problematic because the length scale is important and is different in mice and rats vs in humans.

I was surprised when I looked at the applications section that they were focused on vaccines and not on daily injectable meds like insulin. In thinking about it more, I think it is due to marketing by the suppliers of the daily injectable meds. They don’t want to lose control of the delivery mechanism by allowing non-needle injection.

This different delivery mechanism probably requires new clinical trials for use in insulin. A 5x difference in biological effectiveness in insulin would be a gigantic deal and could even kill people. Vaccines have a much wider acceptable dose range.

The antibody reaction is still going to take the same time scale, so what Dr Novella said about it not being GBS is probably still true. No matter how many vaccines you get it still takes a while to develop the antibodies. You might develop more antibodies but the time scale would still be weeks. But the non-antibody immune response might be higher and that is probably what caused the prompt effects. If so, then worrying about it will likely only make it worse. (stress all by itself acts as an adjuvant).

So I likely had a reduced quantity of the vaccine with the PharmaJet, but may have had a larger antibody reaction due to method it was administered? Is that correct?

http://www.pharmajet.com/applications.html

To me, this suggests that the skin trauma from the jet injection is acting as an adjuvant.

At most it could have a local effect at the site where there was tissue damage. Any effects remote from that site (and I assume the nerve tingling was remote), have to be mediated by a mechanism that is either local to the site of tingling, or a mechanism that affects the neural pathway back to the brain.

Maybe the dosing is not as precise as with injection via needles, but it is hard to imagine it being off by even a factor of two. Maybe there is some difference in how the dose distributes itself in the tissues, as a single large bolus (via needle injection) or with lots of little microtraumas (the jet injection).

When cells are damaged and spill their contents into the extravascular space, some of those cellular contents do act as adjuvants. Maybe there is a difference between the immunological effects of a jet administered vaccine compared to a needle administered vaccine. When the jet device was FDA approved, what drugs were administered with it to show equivalence to needle injection? I presume things like insulin which have to be injected multiple times per day, rather than vaccines which (mostly) are injected only once in a person’s lifetime.

I received both my seasonal flu shot and H1N1 shot using the new PharmaJet technology, which is a needless system of injecting the vaccine. The jet injectors create a fine stream of pressurized liquid that penetrates the skin to deliver the vaccine.

I wonder if there has been any common thread of increased tingling/nerve pain from those that had a PharmaJet delivery?

Antibodies take a certain period of time to form, the antigen has to be taken up and various immune cell things have to happen and then the antibody producing cells have to clonally expand until they start producing enough antibody to have the effects, so prompt neurological effects (few days) are almost certainly not GBS (unless coincidental with an earlier infection and unrelated to the vaccination).

Antibodies are not the only mechanism by which inflammation can be caused. There are plenty of pro-inflammatory cytokines that are promptly released in response to immune system activation. I suspect that those other pro-inflammatory cytokines would be the cause of tingling from vaccines.

I am always interested in nitric oxide effects, and during conditions such as sepsis, the NO level becomes very high, high enough to cause systemic hypotension. NO also inhibits mitochondria by inhibiting the binding of O2 to cytochrome c oxidase. During sepsis, in muscle cells (measured by biopsy and I think the same thing happens in essentially all non-nerve cells), mitochondria are “off” due to the high NO levels (which also causes high ATP (via sGC) which also turns off mitochondria). In nerve cells, mitochondria can’t be turned “off” because nerve cells don’t do glycolysis to make ATP. In nerves, the NO level at the location of the mitochondria has to be kept below a certain level (so that the mitochondria remain on). One way to do that is to produce neuroinflammation on the outside of the nerves, so that the NO gets consumed before it can diffuse inside. The myelin coating of nerves is transparent to NO, but the alternating layers of lipid and aqueous phases would significantly spread that NO out along the length of the nerve (NO is 10x more soluble in lipid than aqueous). This would allow a few NO sinks along the axon to control the NO concentration along the length of the axon.

There are some other neurological conditions caused by antibodies, for example Sydenham’s chorea which is caused by anti-strep antibodies (which is why it is always important to treat strep infections with antibiotics before a high titer of antibodies can form). A significant cause of death before antibiotics was strep infection, in particular puerperal fever. Nitric oxide prevents Strep (and other bacteria) from forming a biofilm, which I think is the reason that sepsis evolved to be a very high NO state. Having bacteria floating around in your blood stream is bad, if they attach and form a biofilm your chances of survival have gone down at least an order of magnitude. Avoiding a 95% chance of death (bacteria forming a biofilm) with a process that has a 50% chance of death (septic shock) is a great evolutionary trade-off.

A major cause of headache is migraine which is known to be due to ischemic preconditioning brought on by superoxide, by neuroinflammation. The headache of fever might similarly be due to neuroinflammation to protect the CNS from too high a NO level. Blocking that neuroinflammation might block the pain, but might also exacerbate potentially damaging high NO effects (because blocking the inflammation allows for higher NO levels). In the context of vaccination, “stress” does act as an adjuvant and so causes the vaccine to produce a more severe immune response and results in a higher antibody titer.

We know there is nothing unique about vaccines that would specifically affect nerves. In particular if there were some sort of “toxin” in a vaccine, at the injection site the level is at least hundreds of times higher than what would occur elsewhere, if there are no local effects on nerves and mitochondria local to the injection site, it is very doubtful that there could be effects remote from the site other than via immune system effects.

Vibration does cause local production of NO. I have an idea that the nerve problems and Raynaud’s following chronic vibration (as in occupational exposure to vibration such as jackhammer use) may be due to a compensatory reduction in NO levels inside nerves to compensate for the chronic local increased NO due to the vibration. The NO/superoxide balance has to be pretty exact to balance each other, and if they get out of whack tingling might be the result.