Last June NeuroImmunology attended the 2011 Biennial meeting of the Peripheral Nerve Society in the Bolger Center, Potomac (MD).
We were obviously interested in disimmune disorders but, we must recognize that, probably, breakthrough, surprising and interesting works were outside our field. Genetic and acquired neuropathies sessions showed, in our oppinion, a higher level than disimmune neuropathies ones.
However, the whole meeting was pretty interesting and some useful conclusions made us think that past work may be starting to give results. I have several comments and remarks regarding disimmune neuropathies:
For me, the first and most important conclussion is the desperate need we have in knowing a lot more of disimmune neuropathies pathogenesis:
- Guillain-Barré syndrome studies are focused almost exclusively in antiganglioside antibodies (which, to date, are the best and more solid research line in these disorders) and don’t seem to point in any other direction, cause or mechanism. However, the ambitious GBS multicentric database projected by Dr Jacobs’ group will, for sure, help in performing other kind of studies, genetic, pathologic and immunopathogenic. We hope we can move on antiganglioside antibodies and see beyond. Dr Huizinga, from Dr Jacobs group, presented their job on dendrictic cell role in GBS pathogenesis and molecules implicated in dendritic cell priming of B cells. It seems that new, non-antiganglioside, works are arising. Regarding antiganglioside antibodies, all posters presented by Dr Willison and Yuki groups were also remarkable.
- CIDP is, by far, the less known of all disimmune neuropathies. We still debate if auto-antibodies or T cells are the effectors. Immunopathogenic studies are scarce, weak and based in imperfect models (modified from multiple sclerosis ones, like experimental autoimmune neuritis – EAN- ). The most remarkable work in CIDP and related diseases was presentation by Gerd Meyer zu Horste, from Dr Kieseier’s lab, showing a new model of CIDP obtained knocking out ICAM-1 in NOD mice. Apart from this job, Dr Kieseier’s group is the only one that consistently publishes in CIDP basic immunology, and that was evident in the number of presentations in the meeting. In the same direction of disease models, Dr Figlia, from Angelo Quattrini group presented a beautiful conference about a model of demyelinating neuropathy caused in mice by an spontaneous mutation on dystroglycan. Although pathological features resembled those of a CIDP it pops up the question if that would fit better with an inherited cause of neuropathy, taking in account that dystroglycan is a necessary element of the extracellular matrix and has nothing to do with immune system (as far as i know). Anyway, beautiful work. Neurofascin was proposed by Dr Pollard group, as a novel antigen for GBS and CIDP. However, antigens detected by ELISA always raise the question if those antigens, detected in their denaturalized situation would be detected as well in conformational, natural situations and, thus, could be pathogenic. But, again, nice stuff to work on.
- Nothing remarkably new was presented in multifocal motor neuropathy and paraproteinemic neuropathies pathogenesis. In anti-MAG neuropathy i liked a work, by an Argentinian group (Dr Lopez and co-workers) on the protective role of MAG for motor neurons.
The other main conclusion i reached in the meeting was that the former (knowing better the mechanisms) should lead to better, more specific therapies. We are blindly trying whatever is being tested succesfully in other diseases and still have not any alternative therapy likely to become a standard treatment in the future, IVIG and steroids aside. We’ve tried Rituximab, Alemtuzumab, Natalizumab… but except the isolated case in which Natalizumab was used, nothing specifically chosen on an immunopathogenic basis. We still are eagerly waiting for a trial with Eculizumab in GBS…
However, among all the IVIg and Rituximab noise, i found an interesting poster regarding therapy. A trial in rats comparing efficacy of a recombinant IgG-Fc compound that could substitute the scarce and expensive IVIg courses. It demonstrated to be as effective as conventional IVIg in EAN Lewis rats. We hope this could be the first step to a novel therapy that could avoid the need of donors that we have now with conventional IVIg.
In conclusion, although several good presentations were worth the trip, we got home the idea that more knowledge of mechanisms and more lab work is desperately needed to move forward in disimmune neuropathies. Unless we prefer to stay stuck to decades-old theories and treatments.
All the abstracts of the meeting can be found online here
4 replies on “What’s going on disimmune peripheral neuropathies”
I have CIDP. Basically my immune system is screwing up, so it is attacking my nerves (specifically the myelin around the nerves) as if they were foreign invaders. This causes nerve death, resulting in increasing numbness or paralysis in my feet and hands. Once the nerves are gone, there’s no getting them back. I’m seeing a neuroligist, which is something of a misnomer. There’s really no problem with my nervous system, per se. It’s more a problem with my immune system. I’m looking for or any way to stop or slow down the demyelination process. Any suggestions that I can pass along to my doctors? The docs around here know very little about CIDP, pushing IVIG again, which had little success on me after six months. Steroids and plasmapheresis have been discouraged by my docs due to side effects, and really do nothing as I understand it for demyelination. Thanks for any leads.
Hello Mr Stewart,
First of all i would like to thank you for your comment in the blog. The aim of Neuroimmunology is not to provide personal counseling to patients but to spread knowledge on these diseases. I’m a neurologist but it would not be appropriate to give an opinion without knowing the case and in a public setting.
Nevertheless i will answer some of your questions because they may be useful for others as well.
CIDP is autoimmune and then, as you say, the immune system is “screwed up”. We don’t know much of CIDP but probably both immune and peripheral nervous system fail together. One attacking, the other not providing proper signals to arrest the attack. Said that, the doctors with the knowledge and skills to treat this disease are neurologists. It’s a rare disease though, so probably not all neurologists are used to deal with it. That means that Neuromuscular disorders departments are the best places to be followed-up.
Several treatments have proven effective in CIDP, but 80% of patients respond to IVIg or steroids or a combination of both. All other treatments provide marginal benefits. IVIg are safe and well tolerated, but expensive and need in-hospital administration. Steroids are, in my opinion, equally safe when taken properly. Steroids’ side effects are well-known and most of the times restricted to the higher doses when used chronically. But higher doses only need to be taken for short periods. An adequate tappering down of the steroids can end up in small doses of steroids that may be sufficient to keep CIDP without progression or, at least, can help reduce the IVIg frequency. Moreover, some studies say that pulsed steroid therapy (very short periodic pulses of high dose dexamethasone) is equally effective with mild side effects. So, steroids are a standard therapy and not necessarily bad-tolerated. Many patients take steroids for many different diseases and have no major problems in the long term. However, as always, this is different for every patient.
Other treatments (plasma exchange, Rituximab, cyclosporin…) have been tested and proven effective but the treatment should rely in IVIg and/or steroids and the others help those two.
Even after having tested every available treatment a significant 10-20% of patients do not respond and evolve to disability, but that’s something that, again, depends on every patient and CIDP features.
Hope this helps clarifying a little bit your doubts. I’m sorry but i can’t provide you personal advise in this blog.
Thank you for the response. It’s more than adequate, even more than I expected. This basically confirms what I already know. I’ve done six months of IVIG, but felt very little improvement. The numbness and pain in my feet continued to increase. My neurologist won’t recommend steroids or plasmapheresis, for some reason.
Then some encouraging news: I started taking alpha lipoic acid, an inexpensive supplement available over-the-counter at WalMart. So far, alpha lipoic acid has made the most noticeable improvements in my CIDP symptoms: definitely less pain; even some regained feeling in my toes. For four months, I’ve taken 1,000 mg. per day, basically mirroring this NIH-sponsored study:
I plan on continuing this at least until the end of the year, at which time I will reassess and reconsider whether or not to continue the more expensive IVIG. Let me know if you have any concerns about taking alpha lipoic acid long term. I may be taking this supplement for a long time, possibly indefinitely.
Shared this with my neurologist. He was completely unimpressed with the alpha lipoic acid, even dismissive, despite the NIH study. He recommends resuming the hugely expensive IVIG, even though it did nothing for me over the past six months. He bases his conclusion on a 1.38 and .64 O-P Amp (mV) gain in two of the recent EMG (electrical nerve conductivity) re-tests. To me, these seem statistically rather insignificant. Whereas the alpha lipoic acid, which is being studied by the NIH, has made a rather significant reduction in my symptoms. For now, I’m sticking with alpha lipoic acid, as long as my body doesn’t disagree with it. May combine that with IVIG shortly.
Hello again, Shawn
I know about the study you mention. It’s interesting, well designed and with a good scientific rationale behind it. However i usually am (in this and many other diseases) against giving my patients drugs that have not proven effective yet. Not only because we don’t know their effectiveness but mostly because they can be harmful. If a patient decides to take a treatment that is under study what i´d say to him is that the best way is inside the clinical trial, if that option is possible in the geographic location where the patient lives.
First because there are many quality controls to ensure effectiveness and to avoid harm.
Second because the patient will contribute to a potential benefit for many people
And third because the placebo effect (something true and often misleading) is properly controlled.
Despite those considerations i don’t think lipoic acid can be very harmful. What i don’t think is good is to withdraw useful medications or not to test other potentially good. Lipoic acid, at this point, should not replace standard therapies. Obviously, if a patient wants to take it anyway what i’d say to him is to take it as add-on therapy, not as a substitute.