I'm wondering if anyone here has any experience with an IV regional block using low-dose tumor necrosis factor-alpha antibody infliximab for RSD/CRPS?

MsL

Dear Ms. L -

Thanks for posting this. I'm willing to bet that you didn't notice in the upper tight hand corner of the PubMed page on which the abstract appears, there's a tag showing that the article is available in free full text at http://www.anesthesia-analgesia.org/...ull/105/4/1148.

I went to the article, the lady in question had CRPS-1 for all of three months. At that point (range) I could name a number of treatments that would be equally effective, including low dose ketamine. Frank Birklein et al are way too sophisticated not to be aware of this little point. As brief as the abstract was you think they could of included that, in constrast for instance to the case report on the successful use of ECT on a woman with refractory CRPS, of 4 years duration, that came out of Dr. Schwartzman's group a few years ago. Treatment of CRPS with ECT, Wolanin MW, Gulevski V, Schwartzman R, Pain Phys. 2007; 10: 573-578, free full text at http://www.rsds.org/2/library/articl...chwartzman.pdf

I suspect there's a lot of academic gaming going on in the German CRPS community. About a month ago I was reading Evolving Understandings About Complex Regional Pain Syndrome and its Treatment, Marcel Fechir, Christian Geber and Frank Birklein, Current Pain and Headache Reports 2008, 12: 186 – 191, and was struck by the fact in their survey of treatment methods, there was no discussion of ketamine, even though Dr. Schwartman sends his patients to Germany for the coma treatment, under the auspices of Ralph-Thomas Kiefer and Peter Rohr. Then I looked at the bibliography, and out of 66 cited articles, none were co-authored by Drs. Schwartzman, Keifer or Rohr, although there were lots of American authors cited.

Then, I ran an author search under PubMed, and although Biklein and Maihofner co-authored 12 articles, niether shared even one article with Drs. Schwartzman, Keifer or Rohr. Same with Franz Blaes, no cross-over with the Ketamine Three.

Something tells me there's a story there. But it's not obvious from the articles I've read. And unfortunately, even the "Advanced Search" features of PubMed don't allow you to search by author AND a word or phrase in the text. For what it's worth . . . .

Mike

is there a difference between the regional block and just going in for a remicade infusion for crohns?

mike

You are right Mike, I didn't see the tag showing the full text.

I thought it was odd that I had not heard anything about it before, but with only one crps patient it doesn't seem as plausible as the abstract indicates. If I had read that I would not have posted this looking for more info.

I can't comment on academic gaming going on in the in the research field, but I have been to Saarbrücken, Germany to talk to Dr. Rohr. He works in a small regional hospital linked to Dr. Kiefer and the university that Keifer works out of. Dr. Rohr told me he would refer me to Schwartzman if I wanted but since my doctor here was already set up with Schwartzman's lidocaine protocols in didn't seem necessary. They are a tight group, but very willing to share their knowledge. Rohr gave my husband and I a 2 hour consult and never charged us a cent, perhaps because we flew all that way to see him.

It was the same thing with the hospital I went to in Schleswig in the north of Germany, just a very small regional hospital with links to the education and research done by Dr. Ralf Baron who is the Head of the Division of Neurological Pain Research and Therapy and Vice Chair of the Department of Neurology, Christian-Albrechts-Universität Kiel, Germany. They have very well educated doctors and staff but you are right I don't see too much cross linking of his research including with the ketamine 3 American or German.

Alsaka Mike you are right it is the same as the remicade infusion for crohns. http://en.wikipedia.org/wiki/Remicade

I'm sorry if this thread gave anyone any false impression. I got a little excited to think there could possibly be an new alternative for us. I'll keep digging though to see if there has been any further developments with Infliximab for CRPS.

MsL

Dear Ms. L -

Although I don't yet have a copy, a fairly detailed abstract to a recent paper suggests that that anti-TNF[alpha] drugs, such as Infliximab (Remecaide) are likely to be effective only in the treatment of accute cases of CRPS, as they were in the study to which you initially made reference:

Systemic inflammatory mediators in post-traumatic complex regional pain syndrome (CRPS I) - longitudinal investigations and differences to control groups, Schinkel C, Scherens A, Köller M, Roellecke G, Muhr G, Maier C, Eur J Med Res. 2009 Mar 17;14(3):130-5

Berufsgenossenschaftliche Kliniken Bergmannsheil, Department of Surgery, Ruhr University, Bochum, Germany. christian.schinkel@ruhr-uni-bochum.de

OBJECTIVES: The Complex Regional Pain Syndrome I (CRPS I) is a disease that might affect an extremity after trauma or operation. The pathogenesis remains yet unclear. It has clinical signs of severe local inflammation as a result of an exaggerated inflammatory response but neurogenic dysregulation also contributes to it. Some studies investigated the role inflammatory mediators and cytokines; however, few longitudinal studies exist and control groups except healthy controls were not investigated yet. METHODS: To get further insights into the role of systemic inflammatory mediators in CRPS I, we investigated a variety of pro-, anti-, or neuro-inflammatory mediators such as C-Reactive Protein (CRP), White Blood Cell Count (WBC), Interleukins 4, 6, 8, 10, 11, 12 (p70), Interferon gamma, Tumor-Necrosis-Factor alpha (TNF-a) and its soluble Receptors I/II, soluble Selectins (E,L,P), Substance-P (SP), and Calcitonin Gene-Related Peptide (CGRP) at different time points in venous blood from patients with acute (AC) and chronic (CC) CRPS I, patients with forearm fractures (FR), with neuralgia (NE), and from healthy volunteers (C). RESULTS: No significant changes for serum parameters investigated in CRPS compared to control groups were found except for CC/C (CGRP p = 0.007), FR/C (CGRP p = 0.048) and AC/CC (IL-12 p = 0.02; TNFRI/II p = 0.01; SP p = 0.049). High interindividual variations were observed. No intra- or interindividual correlation of parameters with clinical course (e.g. chronification) or outcome was detectable. CONCLUSION: Although clinically appearing as inflammation in acute stages, local rather than systemic inflammatory responses seem to be relevant in CRPS. Variable results from different studies might be explained by unpredictable intermittent release of mediators from local inflammatory processes into the blood combined with high interindividual variabilities. A clinically relevant difference to various control groups was not notable in this pilot study. Determination of systemic inflammatory parameters is not yet helpful in diagnostic and follow-up of CRPS I. [Emphasis added.]

PMID: 19380284 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum

I am trying to get a copy of this article as soon as I can, and will at once post as to it's availability. But if it's results check out in subsequent studies, there is no reason to think that any of the anti-TNF drugs would be useful in treating chronic cases of CRPS. That said, the whole question of the role of Calcitonin Gene-Related Peptide (CGRP) as either a product of or a predicate for chronic CRPS ("p = 0.007") opens all sorts of vistas. For starters, "Calcitonin Gene-Related Peptide AND brain" just produced 1,244 hits on PubMed.

But back to the topic at hand, and has been pointed out in other threads, Remicade (Infliximab) has a black box warning that's way scary. Check it out at http://www.nlm.nih.gov/medlineplus/d...s/a604023.html A while back, I saw a rheumatologist who suggested that I consider treatment with Remicade, in conjunction with the use of what I later learned was an even scarier drug, Methotrexate, the Medline blurb for which appears at http://www.nlm.nih.gov/medlineplus/d...s/a682019.html (I said pass.)

Finally, unless someone has the facts to correct me, it's my understanding that the other thing about even trying to use Infliximab (Remicade) for the treatment of CRPS is that it's a strickly off label use of a very expensive drug, so there's no possibilty of insurance coverage, at least for those of us in the ol' US of A.

Mike

I've taken remicade for crohn's. Any questions please email me to my account.

Did you try a Boolian (sp?) search? "smith AND crps" for example...

Haven't tried it with CRPS but have been sucessfull with other topics. Just a thought....

Mike, I am not sure if this is what your talking about, but I just typed in "Schwartzman AND ketamine" and got 6 hits.

To be clear. Yes, there should be lots of articles by Robert Jay Schwartzman, M.D. about ketamine.

My point was that Birklein et al failed to list even low dose ketamine as one of a number of treatments, where we know it's gaining widespread acceptance around the world - particularly for acute cases - but they then (for whatever it's worth) buttress their ostensibly encylopeadic article with 66 carefully chosen citations, including all of the big names in the U.S., but not that of Dr. Schwartzman, who has been the senior and perhaps most prolific guy here for decades.

Then when you look at who writes with whom, distinct cluster patterns emerge. To the point that neither of Dr. Schwartzman's German collegues ever publish with the leading RSD academics in their own country.

It's almost as though the Birklein/Maihofner/Blaes group doesn't acknowledge the existence of Drs. Schwartzman, Kiefer and Rohr, or, more importantly, their work. And yet I've seen nothing in the literature in which they attack the use of ketamine either: to the point that running either Birklein or Maihofner or Blaes AND ketamine yields the null set. Something is going unsaid.

Mike

For what it's worth when I meet with Dr. Rohr in Germany in 2005 he told me that they were stopping the low dose ketamine clinical trials because they did not have successful results with the 10 day low dose trail. He then recommended IV Lidocaine of which I have had good results. Attached is a copy of that abstract published in the American Society of Anesthesiologist Annual Meeting Abstracts.

I know little about about the the politics of these academic circles, research networks, funding and the publishing of papers but I don't think anything is intentionally going unsaid. I have been told that there is always lots at stake including egos when it comes to the academic research regardless of the country researchers and doctors are from. If they are not connected than they are simply not connected academically or financially.

I do however think that most of the low dose ketamine treatments being offered around the USA are more geared towards the revenue generating business models.

Back to the OP about Michael Bernateck et al, they concluded the following:

Perhaps the author(s) have something against the "ketamine 3" as you call them. Perhaps the author (s) are trying to drum up funding for there own research and clinical trial, who knows? Could more be done to investigate this drug inflliximab for CRPS? Perhaps, but with everyone jumping on the ketamine money wagon I doubt that will be done.

MsL

Attached Files

ASA Abstracts -Dr. Rohr 10 day Ketamine.pdf (33.4 KB, 129 views)