What's New in SPINE RESEARCH?

WARNING: The information on these pages is for educational purpose only and should never be used to make decisions regarding your health care. Please bring this information to your physician for further discussion.

The opinions put forth in these writings are not necessarily those of my employer.

Thanks goes out to www.pubmed.com for providing many of these great abstracts which are available to the general public free of charge. However, keep in mind that abstracts can be deceiving as they often don't tell the whole story--you really need to read the whole paper to get a complete understanding.

Typos: I use Dragon NaturallySpeaking to create these pages which sometimes makes mistakes. Please be forgiving of these errors and don't email me-- I just don't have the time to edit these pages.

Home | Research Corner

11/10/13: Randomized, Double-Blind, Placebo-Controlled, Trial of Transforaminal Epidural Etanercept Injection for the Treatment of Symptomatic Lumbar Disc Herniation. There appears to be a "trend" demonstrated that entanercept might help with sciatica when compared to a mystery placebo. But there are some problems with the study.

As I become more familiar with the world of spine research (I am now a professional spine researcher and a published author of several papers), I am getting stricter about what I post on this page – study results can be easily manipulated to favor either side of an outcome. In fact, my goal is to only review randomized controlled trials (one of the highest levels of clinical evidence) that were published in one of the three or four high impact spine Journals.

In 2013, the Australian team of Freeman et al. [1] published the results of their randomized, placebo-controlled trial (the highest possible level of scientific evidence) which apparently demonstrated that epidural injections with a historically-controversial drug (entanercept), actually significantly reduced (significantly = p<0.05 = this means the results, as calculated via statistics, had a 95% chance of being a real and not a fluke) lower limb pain and low back pain (that was a surprise) as compared to a placebo in patients suffering lumbar disc-herniation related sciatica – at least they were doing this good six months after the procedures (which is still not very far out).

Hold on, not so fast. I was absolutely shocked to see that they were declaring the results as significant by using an inferior measuring stick (P-value or alpha-value). The gold standard measuring stick for achieving that magical statistical significant mark is P<0.05.  These authors appear to have gotten away with using P<0.1, which means these results are 90% accurate and have a 10% chance of being not true (there’s a little more to it than that description, but it works).

So what you can really conclude from this study is that in the very short term (i.e. six months) entanercept epidural injections have a “trend” (trend = any result that statistically weighs in between p=0.10 and p=0.05) to decrease the pain of sciatica, as well as low back pain.

Criticisms:

It was very surprising that the Journal SPINE, which is one of the high impact spine journals, actually allowed these authors to use a P value of 0.1.  Such a thing is really unheard-of in the world of research for it can be misleading. The other strange thing is that the placebo was not described – you always describe the placebo!  Why does it seem that many papers which investigate entanercept for sciatica are shrouded in controversy? Another big problem with the study is that entanercept wasn't compared against the gold standard, which is a steroid injection ( which is most likely must less expensive ). Really too bad they didn't tell us what the placebo was, and frankly I don't understand why the secrecy?

Reference:

1) Freeman BJ, et al. Randomized, double-blind, placebo-controlled, trial of transforaminal epidural entanercept for the treatment of symptomatic lumbar disc herniation. Spine 2013; 38:1986-1994.

7/5/2013: I have reviewed the U.S. paper (Fu et al. - 2013) and was disappointed with some of its methodology. They were afforded a rare opportunity: they got the raw patient data from 13 randomized controlled trials (1,879 total patients) and could have easily assessed the efficacy of BMP-2 with regard to Heterotopic bone, pseudoarthrosis and osteolysis, but they didn't. Although the most important issue at stake was cancer, to which they concluded that the patients who had fusion augmented with rH-BMP-2 had a little over three-times the risk of developing cancer postoperatively as compared with patients who didn't have the BMP. Confusingly, however, they admittedly failed to include the results from seven investigations (429 patients) which did not demonstrate a single case of cancer after BMP (I have emailed the editor and authors asking for clarification as to why they did not include this information, which seemingly may have affected the results). There were also important typographical errors (really ridiculous for a paper that apparently cost over $1 million to write). They also claimed that BMP had no advantage over iliac crest bone graft (which is traditionally used) with regard to clinical outcomes, rate of fusion, or perioperative complications. Unexplained postoperative radiculitis was not more prevalent with BMP. The authors concluded, "More research is needed to provide more reliable estimates of risk for cancer and other adverse events...."

I agree with one thing, more quality research is needed on rH-BMP-2. Your decision whether or not to use rH-BMP-2 to augment your fusion, all comes down to this (based upon our current knowledge of rH-BMP-2): if you use it, your chances of successful fusion will be enhanced and occur more rapidly and you will not have iliac crest harvest site morbidity (i.e. chronic pain in the hip). However, there appears to be a small chance for complications such as osteolysis or heterotopic bone which might need surgical decompression. There also appears to be a small risk for the development of postoperative cancer, although we just aren't sure just yet. They did note that most of the cancer cases came from earlier trials of BMP which used much much higher concentrations of BMP, which was confirmed in the Carragee paper. We are still using it at our clinic and I am working feverishly to study its outcomes and complications (we have one study awaiting publication and a very large study awaiting and Medtronic grant which will take a close look at how this affects patients health at about four years postop--if they our brave enough to let us proceed, it will be the first study to specifically assess change in health status after fusion augmented with rH-BMP-2). Hats off to Dr. Corenman for caring enough about his patients to allow us to investigate the sensitive subject.

6/19/2013: Oh this is a big one! Because of the Carragee paper of 2011, where he insinuated researchers were paid millions of dollars in exchange for favorable papers supporting the osteobiologic rhBMP-2, rhBMP-2's manufacturer (Medtronic) page $2.5 million to a prestigious Yale research Institute to independently assess the last 10 years of rhBMP-2 research (i.e., publish a meta-analysis). Yale hired two group of researchers to independently assess the previously published industry sponsored trials (Medtronic paid for these studies) with the raw data that was used to create those studies. The bottom line was that the USA researchers said basically rhBMP-2 doesn't work any better than natural bone (which has to be taken from the patient's hip or from a cadaver) and there may be slightly increased health risk, including cancer, associated with the product. The European group of researchers, naturally came up with slightly different conclusions: rhBMP-2 does increase the speed of successful fusion; however, it does not afford better clinical outcomes. According to the New York Times, (I still have to read these two papers) neither the British nor American teams found a significant difference (P >0.05) between BMP-augmented fusion and traditional fusion with regard to important clinical effects, such as reducing patient pain and increasing physical function.  That is a huge, huge statement, and, if true, is going to cost Medtronic millions of dollars in revenue. But more importantly, how does this new research effect the patient? If BMP goes away, there's no doubt in my mind (based upon hundreds of hours of researching the subject) there will be a significant increase in the rates of pseudoarthrosis (failure to fuse, many of which will necessitate revision surgery – which is going to decrease the chances of successful outcome) and iliac crest graft site morbidity (in other words, many are going to suffer chronic hip pain from the hip bone was harvested [cut out] in order to do that fusion surgery). On the other hand, it potentially could save patients from the long-term development of cancer – although there really is no significant evidence, so far, that demonstrates such a risk (in our own Grant proposal to Medtronic, this is one of the topics we are going to be closely investigating – no one has ever done this before).

7-4-13 Comments: don't get me wrong, the possible link between rH-BMP-2 and cancer is extremely important; however, it was disappointing to me that the New York Times completely failed to mention the two main reasons why many spine surgeons use BMP: 1) it significantly decreases pseudoarthrosis (failure to fuse) and completely eliminates the chance of chronic pain secondary to iliac crest bone harvest (taking bone from the patient's hip and using it for the fusion procedure). It really seems like this article demonstrates some bias against Medtronic (I mean why not present the other side story?) And by the way, you should know I have absolutely no financial ties with Medtronic – they have never paid me a single penny. There is no question in my mind that initial investigators, who were sponsored by Medtronic, should have reported/picked up on the well-known phenomena that is absolutely associated with the use of BMP, such as the development of osteolysis and heterotopic bone formation and, ostensibly, and unexplained postoperative radiculitis.  In the paper we have submitted toThe Spine Journal, we found approximately 30% of our patients develop these BMP phenomena following its use; however, it was not related to anything: clinical outcomes, perioperative complications, rate of revision surgery, or return to work status – statistically speaking it was just a finding demonstrated on MRI and/or CT scan. In layman's terms, at an average follow-up of almost 4 years, the patients who developed the BMP phenomena did just as good as patients who didn't. And by the way, this group of patients, although small (n= 26) had a 90% median patient-satisfaction rate, which I would have never believed possible of any fusion technique if I wouldn't have seen the results with my own eyes-- but this is another story and I will certainly post a link to the paper once I get it officially published in one of our high impact journals.  Have a great Fourth of July everybody!

6-15-13: For people with chronic back and leg pain, it’s important to stay focused while performing tasks such as the bending, lifting, and twisting which are needed in order to execute many of the activities of daily living. In other words, you need to think about using proper mechanics in performing these activities. Why? Because if you don't concentrate, you're going to increase the forces placed upon the lumbar vertebrae and discs, which may lead to a flare-up! In a brilliantly designed study, Katsuhira et al. used a biomechanical laboratory to calculate the amount of force placed on the lumbar vertebrae/discs during the performance of lifting/bending techniques. The surprising finding was that if the subjects were made to think about other things (they were required to do mathematical problems in their head) while performing the lifting/bending activities, the stress and strain measured within the lumbar vertebrae and discs greatly increased (this increase did reach statistical significance). So if you want to avoid flare-ups, think about what you're doing when it comes to lifting, bending or similar challenging activities.
Here is a picture of the setup they used in order to obtain readings used to mathematically calculate loads within the lumbar spine.  We have plans for a very similar study in our biomechanical laboratory only we will be taking it a step farther by putting lumbosacral supports (back braces) on the test subject in order to see if they really do any good.


6/14/13: here's another meta-analysis/systematic review that compared 23 high quality previous studies (pooled the data to make a super study) regarding outcomes following epidural steroid injections for sciatica. As many of us who went through these procedures already know, they do work pretty good for the short-term but have no effect in the long term, which is unfortunate. In other words, if you are having severe pain they might be useful to get you through the rough patch, but that's about it.

ESIs do not work

6-14-13: here's an important meta-analysis (meta-analysis = one of the most powerful types of research papers out there which use only the highest quality research papers published on a specific topic [in this case antitumor necrosis factor alpha treatments for sciatica] and pools the patients each of them used to create a statistically powerful opinion of the topic) on the subject of anti-tumor necrosis factor alpha treatments for the dreaded sciatica. As I have been saying for years, according to this meta-analysis, this type of treatment just does not work for sciatica– so don't waste your money. The forthcoming is an abstract of the study:

3-24-13: reviewed a exciting new technique/paper (intradiscal biacuplasty) for the treatment of chronic lumbar discogenic pain. The paper, which was a randomized placebo-controlled trial (a very rare type of experiment), demonstrated that biacuplasty was statistically significantly better than a placebo (which was a fake intradiscal biacuplasty) as patients in the treatment group were better after the procedure with regard to pain, activities of daily living and disability. Read all about it here.

3-29-12: Swollen Sciatic Nerves: A Turkish team performed ultrasonic assessments of the sciatic nerves of patients in whom were suffering lower back pain with sciatica. They concluded, "Sciatic nerves seem to be enlarged on the side of sciatica in patients with low back pain." [Here]

3-23-12: New page -- which is long overdue -- on Open Discectomy / Microdiscectomy [here].

3-4-12
: New Page (lot of work on this one) on a minimally invasive treatment for those pesky small contained disc herniations: Nucleoplasty.

2-29-12: I completed my page on automated percutaneous lumbar discectomy (APLD), which is the most commonly performed minimally invasive form of discectomy to date. May work, but only for a very narrow window of patients. [here]

February 28, 2012: I reviewed and published my second systematic review on percutaneous laser lumbar discectomy – this time and evidence-based US study [here]. The disc herniation page has also been updated to reflect new evidence [here]. I should have a review of all minimally invasive procedures published by tomorrow or the next day.

February 26, 2012: HOLD THE PRESS! in 2009, Carragee reversed his opinion on the long-term effects of needlestick injury in an incredible investigation (it won the prestigious ISSLS Prize that year). More specifically, this all Stanford team of researchers reported the results at the 10 year time point of a prospective study in which 75 subjects without serious low back pain initially underwent MRI and discography in 1997. As a control group, 75 subjects--none of whom had any pain--were matched to the experimental group with regard to gender, job and body morphology; they all underwent MRI scans but did not undergo discography. At the 10 year time point, another MRI was performed on all participants. The results were surprising (not to me): unlike the four-year Carragee study (which showed no ill effects from discography stick), this time there were big, statistically-confirmed differences between the two groups. More specifically, the discs that had been exposed to puncture and injection had a greater progression of degenerative findings compared to the control (non-injected) discs. With regard to new disc herniation, there were 55 new herniations in the discography group compared to only 22 in the control group (p = 0.003), and these herniations "were disproportionately found on the side of the annular puncture (p = 0.0006). Furthermore, disc height loss as well as a loss of disc signal also was greater in the discography group. Carragee concluded, "Modern discography techniques using small gauge needle and limited pressurization resulted in accelerated disc degeneration, disc herniation, loss of disc height and signal and the development of reactive endplate changes compared to match-controls. Careful consideration of risk and benefit should be used in recommending procedures involving disc injection." I told you so! [here's the abstract.]

February 23, 2012: here is a very interesting rat study by the famous Kjell Olmarker, which used four groups of rats (all of which had the thecal sac and lumbar nerve roots exposed surgically) to demonstrate that osteophytes and nodules (precursors to disc herniations) resulted from either exposure to nucleus pulposus (from a donor rat) or from a needlestick injury to the intervertebral disc. So it would seem that an annular tear will lead to a drainage of intradiscal biochemicals, which in turn harden once outside the disc into a disc herniation. Here's the free paper:

February 21, 2012: I published my review of a meta-analysis of an FDA approved minimally invasive procedure called percutaneous laser disc decompression
[Here].

February 13, 2012: I published a new review of an investigation into the phenomenon of centralized pain, which affects some unlucky patients. What's that? As this research paper will demonstrate by fMRI, the brains of some chronic back pain patients (as well as patients suffering fibromyalgia) have been re-wired so to speak and have developed the ability to feel pain secondary to low levels of painful stimulus ( or They feel pain when they shouldn't be feeling anything as the control group will demonstrate). Another very impressive study by Nachemson elf. [Here]

February 8, 2012: I'm on a roll! I added two new investigations to my "current research page." The first one was a five year follow-up study to assess the efficacy (did the damn thing work) of ACDF performed completely through an endoscope [here]. The second one was a double: two rare randomized double-blinded placebo controlled trials (you cannot get a better study than this) assessing the efficacy of IDET and PIRFT for the treatment of symptomatic lumbar annular disc errors [here].

February 3, 2012: I feel like I have just given birth. After five straight days of work, I have just published a page dedicated to one of the best research papers I have ever read. This paper was devoted to reassessing the safety and efficacy of the newly FDA approved cervical artificial discs. It's a must read for any patient considering undergoing the traditional anterior cervical discectomy fusion (ACDF). It is my layperson opinion, that for a select group of patients, cervical artificial disc is the way to go (it is rare for me to jump on the bandwagon with regard to spinal procedures, but this is an exception--there has been the changing of the guard. [Here]

January 29, 2012: Added rare investigation that used MR Neurography to work-up patient who had sciatica without the usual causes. Here.

January 19, 2012:  getting closer to a cure for sciatic pain? Tumor necrosis factor alpha AND interleukin-1beta inhibitors: the one-two punch treatment: The Swedish star researcher, Kjell Olmarker, has just published the results of the most interesting 2011 experiment using sheep (the sheep disk has a structure and composition that is incredibly similar to that of humans). We are pretty sure these days that a merry band of pro-inflammatory cytokines (tumor necrosis factor alpha, interleukin one beta, interferon gamma, interleukin six) are responsible for the horrible, radicular pain of sciatica. Tumor necrosis factor alpha, the leader of this merry band of biochemicals, has been the main target of therapeutic intervention. Unfortunately, experiments seem to demonstrate that its inhibition (i.e., stop it from doing its thing) only partially ameliorates the symptoms of sciatica. Since tumor necrosis factor alpha's genesis/function is obviously intertwined with the other cytokines, Olmarker designed an experiment that not only blocked tumor necrosis factor alpha, but also blocked another evil cytokine called interleukin-1beta. CONCLUSION: the results of this study, perhaps surprisingly, demonstrated that the inhibition of both cytokines (tumor necrosis factor alpha and interleukin-1beta) decreased radiculopathy (they could tell this because the nerve conduction testing was more greatly improved after inhibiting both of these cytokines) as compared to blocking tumor necrosis factor alpha alone or blocking interleukin-1beta alone. [HERE is a copy of the entire article which Dr. Olmarker graciously posted on the web for free—what a guy!!!]

Here's a link: http://www.ncbi.nlm.nih.gov/pubmed/21584204


January 19, 2012
: Tumor necrosis factor alpha is still the king! I have yet to find anything more recent than this 2002 study (Spine--Aoki, Olmarker, et al) – I guess it is pretty well established that tumor necrosis factor alpha is the culprit in nerve root dysfunction following exposure to a herniated disc material (i.e. nucleus pulposus). THE STUDY: Basically what the investigators did in this study was to apply (after laminectomy) the following biochemicals onto the exposed nerve root/cauda equina: nucleus pulposus, tumor necrosis factor alpha, interleukin-1beta, and interferon-gamma. To keep this study real, some of the pigs received a placebo [autologous fat]. Nerve root conduction studies were then performed in order to test how well those nerves were functioning after application of the biochemicals. RESULTS: although interleukin-1beta and interferon gamma produced a slight injury to the nerve roots (i.e. a slight decreased nerve conduction speed), nucleus pulposus and tumor necrosis factor alpha application resulted in marked nerve root injury. Tumor necrosis factor alpha's affect on nerve root/nerve conduction speed was even more destructive than nucleus pulposus. Note:Paradoxically, however, we learned from Olmarker's 2011 study that with regard to inhibition, you have to block both tumor necrosis factor alpha, as well as interleukin one beta in order to improve nerve conduction velocity – which should translate into decrease radicular pain of sciatica.

Here's a link: http://www.ncbi.nlm.nih.gov/pubmed/12163720

*January 19, 2012: here's an interesting and rather scary investigation by Rohan and Ohnmeiss (and others) that was published in Spine J in 2009.  After studying 232 patients who were involved in the FDA trials comparing fusion versus total disc replacement, the investigators discovered a startling phenomenon: the major predictor of postsurgical success was not the type of surgery but how along the patient waited before having the surgery. The magic number in this investigation seem to be 13 weeks. More specifically, patients who waited longer than 13 weeks to have there fusion/disc replacement surgery, did not respond as well to the treatment. This result flies in the face of a Volvo award-winning study in the early 2000s that determined time was not an issue with regard to fusion.

The reason I say this is scary is because fusion is forever. Failed fusion surgery can result in a devastating loss of the activities of daily living – patients have committed suicide secondary to failed fusion. The notion of waiting only 13 weeks is absurd in my opinion. There must be something more behind these numbers..

Here’s a link: http://www.ncbi.nlm.nih.gov/pubmed/18809357


January 19, 2012
: here's another interesting investigation by Leahy, Ohnmeiss et al. that was performed in 2008. They wanted to find out whether or not fresh never-before-operated-on patients did better than patients who had undergone subsequent surgery. The bottom line of this small investigation was that there was no difference with regard to outcome between the two groups. In other words, patients who have had prior surgical procedures did just as well with total disc replacement (ProDisc in this case), as those who had never undergone surgery.

Here's the link: http://www.ncbi.nlm.nih.gov/pubmed/18580740

*January 19, 2012: this was a big one! The results of the 2005, prospective, randomized, multi-center Food and Drug Administration trial into the efficacy (did the damn thing work) of artificial disc replacement (a.k.a. ADI or total disc replacement) as a treatment for chronic discogenic pain. More specifically, researchers Blumenthal, Ohnmeiss, et al pitted the CHARITE artificial disc system against traditional lumbar interbody fusion. Of course the patients were randomized into either the CHARITE group or the traditional fusion group (that means they picked a straw and whoever got the short straw went to the traditional fusion group and whoever got along straw went to the CHARITE group—well it wasn't that crude but you get the idea).  The ratio was 2:1.  After a two-year follow-up the results not only demonstrated that the CHARITE system was efficacious (it worked), it (perhaps surprisingly) outshone the traditional fusion technique. "The CHARITE artificial disc group demonstrated statistically significant superiority into major economic areas: a 1-day shorter hospitalization and a lower rate of reoperation (5.4% compared with 9.1%). At 24 months, the investigational group had a significantly higher rate of satisfaction (73.7%) than the 53.1% rate of satisfaction in the control group. This prospective randomized multi-center study also demonstrated an increase in employment of 9.1% in the investigational group (i.e. the CHARITE system) compared to a 7.2% employment number for the control group."
What's the bottom line? It appears that the CHARITE not only works, but does a better job than traditional fusion. And of course we know from other studies that all forms of artificial disc reduce the "dominoes effect.” (What is the dominoes effect?,,,,,,,,,,,,,,,,,,, traditional fusion fuses to vertebrae together, which in turn increases the workload on the adjacent vertebral discs and bones, which in turn creates degeneration, which in turn increases the likelihood of new herniation/angular tears at adjacent levels. Artificial disc/total disc replacement allows motion between segments and prevents the dominoes effect.

Here's a link: http://www.ncbi.nlm.nih.gov/pubmed/16025024

January 19, 2012:  an older investigation by Ohnmeiss and Rashbaum (2001), which demonstrated that approximately 50% of patients of whom suffered chronic intractable low back pain responded well to the implantation of a spinal cord stimulator. It was a small study (41 patients) which was retrospective. The results were based on the completion of patient questionnaires. The most interesting number was the result that 75% of the patients "you have the procedure performed again if they had known there outcome before implementation." In other words, 75 patients would do it again if they could have a "do-over.” That's really not a bad number.

Here's a link: http://www.ncbi.nlm.nih.gov/pubmed/14588316

January 19, 2012: is a very small but interesting Swiss follow-up investigation into the long-term outcome of ProDisc-L II in 14 patients.  This 2011 investigation (Markwalder et al) concluded that at an average of 6.5 year follow-up, 10 of the patients (71%) still had an excellent result from the surgery. Two of the 14 reported a good outcome; one of the 14 reported a fair outcome and one of the 14 (7%) reported a poor outcome. Unfortunately the abstract did not define the excellent, good, fair, and poor. The other interesting tidbit was the claim that the improvement was only "slightly higher" at 6.5 years from 1.5 years.

Here's a link: http://www.ncbi.nlm.nih.gov/pubmed/22099076

January 19, 2012:  here's an interesting one from Stanford's Carragee et al (2011): they wanted to test a theory that patients who have a complex of molecules within the epidural space (the space that surrounds the nerve roots and disc for that matter) respond better to epidural steroid injections for the treatment of disc herniated related sciatica. More specifically, they were looking for a complex of fibronectin and aggrecan that was present in the epidural space. In the patients who had this complex of biomolecules, the ultimate response to the epidural steroid injections was much greater/more favorable than patients who lacked this complex. What is it all mean? It means that these two biomolecules must somehow react with the corticosteroid in a way that negates the effects of inflammation.  Now we just have to figure out a way to screen patients for these molecules without entering the epidural space with a needle.

Here's a link: http://www.ncbi.nlm.nih.gov/pubmed/21224775

January 19, 2012:  here's a study all those doctors who perform nucleoplasty are not going to like: the study was done by Carragee, Cuellar et al in 2010. The goal of the investigation was to further investigate claims by nucleoplasty doctors that this procedure "reduces disc protrusions, improves disc hydration (i.e. diminishes the blackness on MRI / rehydrates the disc), and restores disc height (from patients who have lost natural disc height do to degeneration). This tiny study (28 patients) took new MRIs of the 28 patients in whom had nucleoplasty, which failed. Not surprisingly, the post MRI studies failed to show any improvement of disc protrusion size, failed to show any diminishment/rehydration of the target disc, or failed to show any increase in disc height. Also (at least to me) not surprising was the fact that 32% of the discs exposed to nucleoplasty actually suffered a worsening of degeneration less than one year after the procedure—“ a rate greater than expected by natural progression….”

Here's a link http://www.ncbi.nlm.nih.gov/pubmed/21131800

January 19, 2012:  here's another interesting study that was performed in 2010 by Cuellar, Carragee et al. this study found that a biochemical called IFN-gamma (interferon gamma {a cytokine}) was not present in the unlucky normal test subjects who underwent discography for the "cause." This biochemical was quite high, however, in the disc substance in patients suffering discogenic pain whose provocative discography was positive. Based on these results, the researchers will continue investigations into this chemical (phase 2).

Here's a link http://www.ncbi.nlm.nih.gov/pubmed/20207331

 *January 19, 2012: the new smoking gun? Another study implicating the cytokine IFNgamma (interferon gamma) as a biomarker for lumbar nerve root irritation. This 2009 study (Scuderi, Carragee et al) followed 47 consecutive patients with lumbar degeneration, low back pain, and or leg pain after giving them an epidural steroid injection (the used depo-medrol! {I thought that was forbidden in this country?}). Right before the injection, samples were taken of the epidural space and tested for the presence of IFNgamma. The results found "IFNgamma was the most consistently detected cytokine." Its presence also predicted the degree of pain relief following epidural steroid injection with greater than 95% accuracy! "These results suggest that IFNgamma may be part of a biochemical cascade triggering pain in sciatica." This cytokine "may serve as the future therapeutic target." "It may also protect response to surgical intervention."

Here's a link http://www.ncbi.nlm.nih.gov/pubmed/19934811

*January 19, 2012:  Autoimmune component to sciatica?  Yes.  This 2009 Swedish study (Geiss, Olmarker et al) speaks about how nucleus pulposus, which is derived from notochord, is “excluded from the development of immunological tolerance.”  So it, when released from the disc, will start the autoimmune response that “starts with antigen capture,” and continues with the activation of T helper cells. The reaction ends with the production of autoantibodies (against the nucleus pulposus).  Also, activated T-helper cells differentiated into “either T-helper-1 cells (these predominantly produce proinflammatory cytokines such as interferon gamma (IFNgamma), or they differentiate into T-helper-2 cells (these produce anti-inflammatory cytokines such as interleukin-4).
In this study, autologous nucleus pulposus was exposed to a pig’s immune system—to see if that would start the inflammatory cascade.  CONCLUSION: Nucleus pulposus (for example, from disc herniation) may prime T-helper cells to develop into IL-4-producing T-helper-2 cells after being exposed to the immune system. Some IFNgamma was also produced.

Here's a link http://www.ncbi.nlm.nih.gov/pubmed/19934811

 

January 15, 2012: Good news for cervical artificial disc replacement fans: the Kineflex-C system (a fake disc system for the neck if you will) bodes well in a 2011, well done, two-year randomized control trial (a high quality type study). The investigators randomized 269 patients (all of whom suffered chronic neck pain secondary to a bad disc) into one of two treatment groups: the Kineflex-C system or the time-test traditional treatment--ACDF (anterior cervical discectomy fusion). At two-year follow-up, the "overall success rate was significantly greater in the Kineflex-C group (85%) compared to the ACDF group (71%)." In both groups, Neck Disability Index "improved significantly" and so did VAS pain scores. Degenerative changes (secondary to the surgery) were also measured and compared between the two groups, which not surprisingly found more "severe" adjacent degenerative changes present in the ACDF as compared to the Kineflex-C system. "However, there were no significant differences between groups in adjacent-level reoperation rate--all though Kineflex-C patients were slightly more prone to need a second surgery (7.6% vs. 6.1%).

Bottom line: It would appear that the two surgical techniques are basically the same with regard to outcome. The artificial disc (i.e., the Kineflex-C system) patients had less "severe" degenerative changes above and below the level of surgery. Remember, the major criticism for the traditional ACDF was that it created degenerative changes above and below the level of surgery, which in turn could necessitate the need for further surgery.

Here's the link:

 

January 15, 2012: Here's a 2011 Swedish study that randomized patients into a traditional fusion group and total disc replacement (artificial disc replacement {ADR}). After a two year follow-up, although the ADR demonstrated good movement between lumbar segments (remember, traditional fusion "fuses" much of the lumbar spine, which may blow-out the non-fused disc above or below), this good movement "WAS NOT CORRELATED TO (good) clinical outcome."

Here's the abstract:

January 15, 2012: Here's a poorly written 2012 investigation from China with an interesting message: provocation discography is apparently not always positive for patients in whom suffer discogenic back and leg pain. More specifically, the researchers said, "The study indicated that negative discography in patients with probable symptoms of discogenic low back pain cannot absolutely exclude the diagnosis of discogenic pain." *Interesting was the fact that about 50% of these patients with bad, tore-up discs (i.e., discogenic pain) suffered anterior or posterior thigh pain in addition for lower back pain. One-hundred percent of them had lower back pain.

Here's the abstract:

November 18, 2011: A wonderful and free research paper (2004) I discovered that was put out by the Mayo Clinic regarding our current understanding of chronic radicular type pain (i.e., neuropathic pain), (such as the burning pain I have right now in my thigh, which occurred for seeming no reason.... ) It's a very advanced read but very instructive; it is aimed at the primary treating physician, which is great to see. I was quite surprised to see there is now evidence that the sympathetic nervous system at the site of injury is now thought to be involved in chronic pain. Take home message is:

chronic_rads

Down load the article here:

March, 2010

Here we go again: another treatment--Precutaneous endoscopic laser annuloplasty-- attempting to treat/decompress a symptomatic annular tear by putting a new hole in an already damaged disc. It just doesn't make sense, for we know that even a tiny shallow hole in the periphery of a disc may cause that tiny hole to progress / grow all the way into the nucleus (you have just created a new annular tear), as well as create degenerative disc disease. In my humble opinion, this sort of treatment is dooming that disc to fusion in the near future. I'm still waiting for a good quality controlled trail with a long term follow-up (this studies follow-up was only 9.7 months!!! {are you kidding me!!!}) to prove any of these disc decompression endoscopic treatments are effective. Why don't they do them?

I bet I know...

Pubmed.com article

March, 2011

What's in that annular tear you might see on your MRI? Nice investigation published in Spine that has the answer. Perhaps not surprisingly, it's TNF-alpha and CD68. These are evil biochemicals that are also implicated in the cause of sciatica.

pubmed.com article

**December, 2010

Here's one (although it's a very small study) for all those nay-sayer docs who don't believe that annular tears by themselves (without the presence of a compressive disc herniation) can cause not only back pain, but also real EMG-confirmed radiculopathy (i.e., sciatica / radiating leg pain). Good to see the Chinese doing research like this--we really need it! Unfortunately, the article was in Chinese, so I was unable to read more about the treatment used "local windowing decompression and debridement of the nucleus."

pubmed.com article

January, 2001

Molecules called chemokines (small cytokines) are now believed to be involved in the natural healing process of annular disc tears. Perhaps this could be a new area of development in hopes of speed healing annular tears, which empirically can take 1.5 years to heal in a degenerated disc. [www.pubmed.com]

 

March, 2011

An interesting investigation:  In a nutshell, it appears that annulus fibrosis cells (oh yes, the annulus fibrosis tissue has its own cells within it), once injured or torn, will trigger an inflammatory process, as well as the development of nerve (which can carry pain) and blood vessel growth in and around the injured annulus. Remember we know from other research that such nerve/blood vessel ingrowth can follow that annular tear inward to the nucleus (normally, no nerves are located in the inner regions of the disc).  So now you have created a disc that is much more capable of “hurting,: when compared to a person without such a torn disc. This would explain why once a patient suffers a bout of severe back pain, they will more likely than not suffer future pain.

Spine. 2011 March 7.  Annulus Fibrosus Cells Interact with Neuron-Like Cells to Modulate Production of Growth Factors and Cytokines in Symptomatic Disc Degeneration.  Moon, Kim, Lee, et al.

Abstract
Annulus Fibrosus (AF) cells are involved in an inflammatory reaction and the interactions between AF and neuron-like cells enhance the production of growth factors responsible for nondisclosure and nerve ingrowth. AF injury has the potential to initiate nondisclosure/nerve ingrowth and an inflammatory reaction through the interactions of AF and neural tissues. Study Design: We hypothesized that AF/neuron interactions during annular injury were involved in neovascularization and nerve ingrowth, the pathologic hallmarks of symptomatic disc degeneration.Objective: To identify growth factors and inflammatory cytokines related to AF/neuron interactions using in vitro model.Summary of Background Data: Discogenic pain is the chronic intractable pain initiated by tears in the outer annulus fibrosus (AF); this is unique structure with free nerve endings at outer one-third, located beside dorsal root ganglia. The relationship between AF and neuron cells in annular injury has not been extensively investigated.Methods: Human AF cells were cocultured with a retinoic acid (RA)-treated SH-SY5Y human neuroblastoma cell line (neuron-like cells). Conditioned media from cells cultured alone or in coculture were assayed for growth factors and inflammatory cytokines using enzyme-linked immunosorbent assays. The responses of the neuron-like cells, the AF cells, and the cocultured group to IL-1β/TNF-α were compared using the same outcome measures.Results: RA-treated SH-SY5Y cells showed significant neurite outgrowth on 7th day; this is a typical morphologic finding of neuron-like cells. Neuron-like cells produced vascular endothelial growth factor (VEGF) and IGF-1 under basal conditions and dose-dependently secreted small amounts of IL-8 in response to TNF-α. Coculturing enhanced the secretion of VEGF, TGF-β1, and β-NGF, and suppressed the production of IGF-1. VEGF in the coculture group and the AF cells was downregulated by IL-1β/TNF-α stimulation. IL-1β/TNF-α stimulation enhanced the production of large amounts of IL-6 and IL-8 from AF cells; IL-1β produced a greater response than TNF-α. The neuron-like cells did not produce detectable amounts of IL-6 or IL-8.Conclusion: These studies suggest that AF cells are involved in an inflammatory reaction and that the interactions between AF and neuron-like cells enhance the production of growth factors responsible for neovascularization and nerve ingrowth. AF injury has the potential to initiate neovascularization/nerve ingrowth and an inflammatory reaction through the interactions of AF and neural tissues.


August, 2011


Although MRI has a documented false positive phenomenon regarding disc-herniation induced back/leg pain, this small study confirms the importance of MRI as a diagnostic tool.  In short, MRI works for detecting the cause of back pain with regard to disc herniation and degenerative disc disease-according to this study.


“MRI Findings are More Common in Selected Patients with Acute Low Back Pain than Controls.” Eur Spine J. 2011 Aug – Hancock, Maher et al.

The purpose of this study is to investigate if lumbar disc pathology identified on MRI scans is more common in patients with acute, likely discogenic, low back pain than matched controls.
We compared rates of MRI findings between 30 cases with low back pain and 30 pain-free controls. Cases were patients presenting for care with likely discogenic low back pain (demonstrated centralisation with repeated movement testing), of moderate intensity and with minimal past history of back pain. Controls were matched for age, gender and past history of back pain. Cases and controls underwent MRI scanning which was read for the presence of a range of MRI findings by two blinded assessors.
The presence of disc degeneration, modic changes and disc herniation significantly altered the odds of a participant being a case or control. For example subjects were 5.2 times more likely to be a case than a control when disc degeneration grade of ≥3 was present, and 6.0 times more likely with modic changes. The presence of a high-intensity zone or annular tear was found to significantly alter odds for one assessor but not the other assessor.
MRI findings including disc degeneration, modic changes and herniation are more common in selected people with current acute (likely discogenic) low back pain than in controls without current low back pain. Further investigation of the value of MRI findings as prognostic factors and as treatment effect modifiers is required to assess the potential clinical importance of these findings.

October, 2011

Does pedicle screw loosening cause pain?   Not according to this small-to-medium sized investigation. This retrospective (after the fact) investigation found that out of 126 patient who had previously undergone fusion surgery, 20% (20 patients) of the patients demonstrated pedicle screw loosening or even breaking at the 1.5 year mark!  However, loosening/breaking notwithstanding, none of that group suffered any pain or disability!  So it would appear that pedicle screw loosening or even breaking is not a cause of chronic pain—at least in this investigation.

NeurosurgFocus. 2011 October;31 (4): E9

“Pedicle Screw Loosening in Dynamic Stabilization” Wu JC, Huang WC, et al.
Object The long-term outcome of lumbar dynamic stabilization is uncertain. This study aimed to investigate the incidence, risk factors, and outcomes associated with screw loosening in a dynamic stabilization system. Methods The authors conducted a retrospective review of medical records, radiological studies, and clinical evaluations obtained in consecutive patients who underwent 1- or 2-level lumbar dynamic stabilization and were followed up for more than 24 months. Loosening of screws was determined on radiography and CT scanning. Radiographic and standardized clinical outcomes, including the visual analog scale (VAS) and Oswestry Disability Index (ODI) scores, were analyzed with a focus on cases in which screw loosening occurred. Results The authors analyzed 658 screws in 126 patients, including 54 women (42.9%) and 72 men (57.1%) (mean age 60.4 ± 11.8 years). During the mean clinical follow-up period of 37.0 ± 7.1 months, 31 screws (4.7%) in 25 patients (19.8%) were shown to have loosened. The mean age of patients with screw loosening was significantly higher than those without loosening (64.8 ± 8.8 vs 59.3 ± 12.2, respectively; p = 0.036). Patients with diabetes mellitus had a significantly higher rate of screw loosening compared with those without diabetes (36.0% vs 15.8%, respectively; p = 0.024). Diabetic patients with well-controlled serum glucose (HbA1c ≤ 8.0%) had a significantly lower chance of screw loosening than those without well-controlled serum glucose (28.6% vs 71.4%, respectively; p = 0.021). Of the 25 patients with screw loosening, 22 cases (88%) were identified within 6.6 months of surgery; 18 patients (72%) had the loosened screws in the inferior portion of the spinal construct, whereas 7 (28%) had screw loosening in the superior portion of the construct. The overall clinical outcomes at 3, 12, and 24 months, measured by VAS for back pain, VAS for leg pain, and ODI scores, were significantly improved after surgery compared with before surgery (all p < 0.05). There were no significant differences between the patients with and without screw loosening at all evaluation time points (all p > 0.05). All 25 patients with screw loosening were asymptomatic, and in 6 (24%) osseous integration was demonstrated on later follow-up. Also, there were 3 broken screws (2.38% in 126 patients or 0.46% in 658 screws). To date, none of these loosened or broken screws have required revision surgery. Conclusions Screw loosening in dynamic stabilization systems is not uncommon (4.7% screws in 19.8% patients). Patients of older age or those with diabetes have higher rates of screw loosening. Screw loosening can be asymptomatic and presents opportunity for osseous integration on later follow-up. Although adverse effects on clinical outcomes are rare, longer-term follow-up is required in cases in which screws become loose." pubmed.com

 

February 2011: Chiropractors are not going to like this one: another powerful meta-analysis of 24 randomized controlled trials were reviewed and revealed  there is, “High quality evidence [suggesting] that there is no clinically relevant difference between SMT and other interventions for reducing pain and improving function in patients with chronic low-back pain. So exercise and medication is just as effective as a trip to your chiropractor when it comes to lower back pain—at least according to this study.  But if you add spinal manipulation to the exercise and medication, you might afford a little better result (there are other studies to support this statement).

Here’s the study:
Cochrane Database Syst Rev. 2011 Feb 16;2:CD008112.
Spinal manipulative therapy for chronic low-back pain.
Rubinstein SM, van Middelkoop M, Assendelft WJ, de Boer MR, van Tulder MW.
Source
Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Center, PO Box 7057, Room D518, Amsterdam, Netherlands, 1007 MB.
Abstract
BACKGROUND:
Many therapies exist for the treatment of low-back pain including spinal manipulative therapy (SMT), which is a worldwide, extensively practiced intervention.
OBJECTIVES:
To assess the effects of SMT for chronic low-back pain.
SEARCH STRATEGY:
An updated search was conducted by an experienced librarian to June 2009 for randomised controlled trials (RCTs) in CENTRAL (The Cochrane Library 2009, issue 2), MEDLINE, EMBASE, CINAHL, PEDro, and the Index to Chiropractic Literature.  
SELECTION CRITERIA:
RCTs which examined the effectiveness of spinal manipulation or mobilisation in adults with chronic low-back pain were included. No restrictions were placed on the setting or type of pain; studies which exclusively examined sciatica were excluded. The primary outcomes were pain, functional status and perceived recovery. Secondary outcomes were return-to-work and quality of life.
DATA COLLECTION AND ANALYSIS:
Two review authors independently conducted the study selection, risk of bias assessment and data extraction. GRADE was used to assess the quality of the evidence. Sensitivity analyses and investigation of heterogeneity were performed, where possible, for the meta-analyses.
MAIN RESULTS:
We included 26 RCTs (total participants = 6070), nine of which had a low risk of bias. Approximately two-thirds of the included studies (N = 18) were not evaluated in the previous review. In general, there is high quality evidence that SMT has a small, statistically significant but not clinically relevant, short-term effect on pain relief (MD: -4.16, 95% CI -6.97 to -1.36) and functional status (SMD: -0.22, 95% CI -0.36 to -0.07) compared to other interventions. Sensitivity analyses confirmed the robustness of these findings. There is varying quality of evidence (ranging from low to high) that SMT has a statistically significant short-term effect on pain relief and functional status when added to another intervention. There is very low quality evidence that SMT is not statistically significantly more effective than inert interventions or sham SMT for short-term pain relief or functional status. Data were particularly sparse for recovery, return-to-work, quality of life, and costs of care. No serious complications were observed with SMT.
AUTHORS' CONCLUSIONS:
High quality evidence suggests that there is no clinically relevant difference between SMT and other interventions for reducing pain and improving function in patients with chronic low-back pain. Determining cost-effectiveness of care has high priority. Further research is likely to have an important impact on our confidence in the estimate of effect in relation to inert interventions and sham SMT, and data related to recovery.

February, 2011: Minimally invasive spinal surgery (MISS) not as good as traditional microdiscectomy. 

This is something I’ve been saying for years.  The medical research data base still does not support the use of minimally invasive spine surgery (the tubular discectomy in this case) for the treatment of disc herniation.  In fact, according to this randomized controlled study (which is a very high quality study), MISS not only was no better than traditional microdiscectomy, it was worse!  That is, “Patients treated with tubular discectomy reported more leg pain and more low-back pain than those patients treated with conventional microdiscectomy.”

Here’s the study abstract::

Neurosurgery. 2011 Feb 26. [Epub ahead of print]
Tubular discectomy versus conventional microdiscectomy for the treatment of lumbar disc herniation: two-year results of a double- blind randomised controlled trial.
Arts MP, Brand R, van den Akker ME, Koes BW, Bartels RH, Tan WF, Peul WC.
Source

1Department of Neurosurgery, Medical Center Haaglanden, The Hague, The Netherlands. 2Department of Neurosurgery, Leiden University Medical Center, Leiden, The Netherlands. 3Department of Medical Statistics & BioInformatics, Leiden University Medical Center, Leiden, The Netherlands. 4Department of Medical Decision Making, Leiden University Medical Center, Leiden, The Netherlands. 5Department of General Practice, Erasmus Medical Center, Rotterdam, The Netherlands. 6Department of Neurosurgery, Radboud University Medical Center, Nijmegen, The Netherlands. 7Department of Neurosurgery, Medical Center Alkmaar, The Netherlands.
Abstract
BACKGROUND:

Transmuscular tubular discectomy has been introduced to increase the rate of recovery, although evidence is lacking.
OBJECTIVE:
To evaluate the 2-year results of tubular discectomy compared with conventional microdiscectomy.
METHODS:
328 patients with persistent leg pain due to lumbar disc herniation were randomly assigned to undergo tubular discectomy (167 patients) or conventional microdiscectomy (161 patients). Main outcome measures were scores from Roland-Morris Disability Questionnaire for Sciatica (RDQ), visual analogue scale (VAS) for leg pain and low-back pain, and Likert self-rating scale of global perceived recovery.
RESULTS:
Based on intention-to-treat analysis, there was no significant difference between tubular discectomy and conventional microdiscectomy in RDQ scores during 2 years after surgery (between-group mean difference (Δ) = 0.6; 95% CI, -0.3 to 1.6). Patients treated with tubular discectomy reported more leg pain (Δ = 3.3 mm; 95% CI, 0.2 to 6.2 mm) and more low-back pain (Δ = 3.0 mm; 95% CI, -0.2 to 6.3 mm) than those patients treated with conventional microdiscectomy. At 2 years, 71% of patients assigned to tubular discectomy documented a good recovery versus 77% of patients assigned to conventional microdiscectomy (odds ratio 0.76; 95% CI, 0.45 to 1.28; P=0.35). Repeated surgery rate within 2 years after tubular discectomy and conventional microdiscectomy was 15% and 10%, respectively (P=0.22).
CONCLUSION:
Tubular discectomy and conventional microdiscectomy resulted in similar functional and clinical outcome. Patients treated with tubular discectomy reported more leg pain and low-back pain, although the differences were small and not clinically relevant.

April, 2011: Forget trying corticosteroids for treating sciatica, this investigation, which was a meta-analysis (a study of all the good studies) indicates that oral corticosteroids are no more effective for sciatica than using a placebo and has more complications.

There goes one my “tricks” for treating sciatica.  A popular alternative treatment for sciatica was recommending for a physician to prescribe a strong dose of corticosteroids.  But this meta-analysis (i.e., a study of the all the high-quality studies) finds such a treatment no better than placebo.

Here’s the study abstract:

Rheumatology (Oxford). 2011 Apr 27. [Epub ahead of print]
Efficacy and tolerance of systemic steroids in sciatica: a systematic review and meta-analysis.
Roncoroni C, Baillet A, Durand M, Gaudin P, Juvin R.
Source
Emergency Department, CHU A Michallon, Grenoble, Rheumatology Department, CHU Hôpital Sud, Echirolles and Pharmacy Department, CHU A Michallon, Grenoble, France.
Abstract
Objectives. The efficacy of pharmacological interventions in sciatica is limited and the use of systemic steroids is still controversial. We aimed at evaluating the efficacy and tolerance of systemic steroids in sciatica. Methods. A systematic literature search was performed in the Medline, Embase and Cochrane databases until February 2010. Randomized placebo-controlled trials evaluating the efficacy and the tolerance of systemic steroids in sciatica were included. Efficacy and tolerance were assessed using the relative risk (RR) and 95% CI with the inverse variance method (RR > 1 means that the event is more likely to occur in the steroid group). We explored the heterogeneity between the studies using subgroup analysis. Results. Seven studies (383 patients) were included. The difference in the rate of responders between both groups was not statistically significant (RR = 1.22, 95% CI 0.96, 1.56). The rate of adverse events was 13.3% for the patients in the steroid group and 6.6% for the placebo group (RR = 2.01, 95% CI 1.06, 3.80). The number needed to harm was 20 (95% CI 10, ∞). Twenty (15.3%) patients in the steroid group and seven (5.7%) patients in the placebo group underwent surgery. A trend towards a higher requirement for spinal surgery was observed in the steroid group (RR = 1.14, 95% CI 0.74, 1.75). The methodological quality slightly influenced the results. We did not find any publication bias. Conclusion. Steroid efficacy is not superior to the placebo in sciatica, but it has more side effects. The tolerance : efficacy ratio indicates against the use of systemic steroids in sciatica.

May, 2011: Epidural Steroid Injection Work, but only in cases where there is not too much nerve compression.

An interesting study co-authored by one of the “gods” of spinal research, Nikolai Bogduk.  The bottom line here is that epidural steroid injections do seem to work for patients with disc herniation induced sciatica IF THE NERVE ROOT COMPRESSION IS NOT TOO MUCH.  That’s right, if your nerve(s) is(are) moderately or severely compressed, then epidural steroid injections are not going to do much good (no better than placebo), and surgery might be the ticket.

Here’s the study:

Pain Med. 2011 May 3. doi: 10.1111/j.1526-4637.2011.01116.x. [Epub ahead of print]
Predictors of a Favorable Response to Transforaminal Injection of Steroids in Patients with Lumbar Radicular Pain Due to Disc Herniation.
Ghahreman A, Bogduk N.
Source
Department of Neurosurgery, John Hunter Hospital Newcastle Bone and Joint Institute, Royal Newcastle Centre, Newcastle, New South Wales, Australia.
Abstract
Background.  Transforaminal injection of steroids (TFIS) is effective for some patients with lumbar radicular pain caused by disc herniation. Factors associated with better outcomes are unknown. Objective.  To identify clinical and radiological features predictive of a favorable response to TFIS. Methods.  Seventy-one patients with lumbar radicular pain caused by disc herniation were treated with TFIS as part of a previously reported, randomized, clinical trial. The clinical features analyzed were the presence of neurologic symptom, neurologic signs, and the duration of sciatica. Radiological features evaluated using magnetic resonance imaging (MRI) were the segmental level of the pathology, the location and morphological features of the disc herniation, the cross-sectional area of the disc herniation and its ratio to the cross-sectional area of the spinal canal, and the grade of nerve root compression. Results.  None of the clinical features was associated with An interesting study co-authored by one of the “gods” of spinal research, Nikolai Bogduk.  The bottom line here is that epidural steroid injections do seem to work for patients with disc herniation induced sciatica IF THE NERVE ROOT COMPRESSION IS NOT TOO MUCH.  That’s right, if your nerve(s) is(are) moderately or severely compressed, then epidural steroid injections are not going to do much good (no better than placebo), and surgery might be the ticket.

09/2009: Excellent Free Research Paper on the Current Theory of Chronic Pain. It's a must read for all docs and patients that can read at that high of a level: Here it is:

05/2009: Etanercept (Enbrel) is back in the news and show some promise for the treatment of disc-herniation-induced sciatica as an epidural injectant:

This drug has been touted as a miracle cure for sciatica in the past, but subsequently failed to stand up against placebo-controled medical trials (i.e., it failed to work better than placebo). This time, however, it showed slight promise when injected via standard epidural steroid methodology. Albeit the study was very small (just 24 patients [6 control patient vs. 18 experimental patients]), and the follow-up period was only 6 months, I agree that a bigger investigation is warranted. But until then, I'm not recommending jumping on the bandwagon just yet.

www.pubmed.com: Anesthesiology. 2009 May;110(5):1116-26. Comment in: Anesthesiology. 2009 May;110(5):967-9. Randomized, double-blind, placebo-controlled, dose-response, and preclinical safety study of transforaminal epidural etanercept for the treatment of sciatica. Cohen SP, Bogduk N, Dragovich A, Buckenmaier CC 3rd, Griffith S, Kurihara C, Raymond J, Richter PJ, Williams N, Yaksh TL. Department of Anesthesiology, Johns Hopkins School of Medicine, Baltimore, MD 21029, USA. scohen40@jhmi.edu BACKGROUND: Recent evidence implicates the inflammatory cytokine tumor necrosis factor as a major cause of radiculopathy. Yet, whereas open-label studies with systemically delivered tumor necrosis factor inhibitors have yielded positive results, a placebo-controlled study failed to demonstrate efficacy. One variable that may have contributed to poor outcomes is low drug levels at the site of nerve inflammation. To date, no studies have evaluated the efficacy or safety of epidurally administered anti-tumor necrosis factor agents. METHODS: A double-blind, placebo-controlled, dose-response study was conducted to evaluate an epidural tumor necrosis factor inhibitor. Twenty-four patients with subacute lumbosacral radiculopathy were randomly assigned to receive two transforaminal epidural injections of 2, 4, or 6 mg of entanercept 2 weeks apart in successive groups of eight. In each group, two patients received epidural saline. A parallel epidural canine safety study was conducted using the same injection doses and paradigm as in the clinical study. RESULTS: The animal and human safety studies revealed no behavioral, neurologic, or histologic evidence of drug-related toxicity. In the clinical arm, significant improvements in leg and back pain were collectively noted for the etanercept-treated patients, but not for the saline group, one month after treatment. One patient in the saline group (17%), six patients in the 2-mg group (100%), and four patients each in the 4-mg and 6-mg groups (67%) reported at least 50% reduction in leg pain and a positive global perceived effect one month after treatment. Six months after treatment, the beneficial effects persisted in all but one patient. CONCLUSION: Epidural entanercept holds promise as a treatment for lumbosacral radiculopathy.

09/2009: 2009 study demonstrates that giving a patient's his/her actual, removed disc herniation after surgery increases the chances of recovery?!!!

Here’s a very surprising 2009 study that truly demonstrates how important and powerful the mind can be with regard to the recovery process following disc surgery (which is good, for we need all the help we can get). And it was even a randomized controlled double-blind study, which is as good as it gets albeit the experimental and control group were a little small.  Believe it or not, patients that were simply given their disc herniation after surgery achieved a much more favorable surgical outcome (i.e., they got much better) when compared to patients that were not shown their disc herniation!  More specifically, 92% of the experimental group (the ones that were given their herniation) had improved lower limb pain versus 80% of the control group (the ones that were not given their herniation); 86% of the experimental group had improved back pain versus 75% of the control group; 91% of the experimental group had an improvement in leg weakness versus 56% of the experimental group etc. (read below for more results).  Although I’m a little skeptical of those ridiculously high improvement rates (no spinal surgery is 90% successful), all in all it’s simply an amazing study that should prompt all spinal surgeons to consider giving patients their excised disc herniations after the surgery.

BACKGROUND: Lumbar microdiscectomy (LMD) is a commonly performed neurosurgical procedure. We set up a prospective, 
double blind, randomized, controlled trial to test the hypothesis that presenting the removed disc material to patients after LMD improves patient outcome. METHODS: Adult patients undergoing LMD for radiculopathy caused by a prolapsed intervertebral disc were randomized into one  of two groups, termed experimental and control. Patients in the experimental group were given their removed disc fragments whereas patients in the control group were not. Patients were unaware of the trial hypothesis and investigators were blinded to patient group allocation. Outcome was assessed between 3 and 6 months after LMD. Primary outcome measures were the degree of improvement in sciatica and back pain reported by the patients. Secondary outcome measures were the degree of improvement in leg weakness, paraesthesia, numbness, walking distance and use of analgesia reported by the patients. RESULTS: Data from 38 patients in the experimental group and 36 patients in the control group were analysed. The two groups were matched for age, sex and preoperative symptoms.  More patients in the experimental compared with the control group reported improvements in leg pain (91.5 vs 80.4%; p<0.05), back pain (86.1 vs 75.0%; p<0.05), limb weakness (90.5 vs 56.3%; p<0.02), paraesthesia (88 vs 61.9%; p<0.05) and reduced analgesic use (92.1 vs 69.4%; p<0.02) than preoperatively. CONCLUSION: Presentation of excised disc fragments is a cheap and effective way to improve outcome after LMD.
J Neurol Neurosurg Psychiatry. 2009 Sep;80(9):1044-6. Improved outcome after lumbar microdiscectomy in patients shown their excised disc fragments: a prospective, double blind, randomised, controlled trial. Tait MJ, Levy J, Nowell M, Pocock C, Petrik V, Bell BA, Papadopoulos MC. Academic Neurosurgery Unit, St George's University of London, London SW17 0RE, UK.
06/2008: Core muscle strengthening... a waste of time?

This is the second study from a reputaible journal that I've seen that casts doubt on the notion that weak trunk muscle strength is related to lower back pain. Maybe all that core strenghtening is unnecessary. (I no longer do it and am doing great!, although I do religously walk.) here's the abstrat... food for thought. Here's the study.

Paalanne N, Korpelainen R, Taimela S, Remes J, Mutanen P, Karppinen J. "Isometric trunk muscle strength and body sway in relation to low back pain in young adults." Spine. 2008 Jun 1;33(13):E435-41.

Department of Sports Medicine, Deaconess Institute of Oulu, Oulu, Finland.
nikopaal@mail.student.oulu.fi

STUDY DESIGN: A cross-sectional study on young adults. OBJECTIVE: To evaluate the relationships between low back pain (LBP), maximal isometric trunk muscle strength, and body sway among young adults. SUMMARY OF BACKGROUND DATA: The
results of previous studies evaluating the association between trunk muscle strength and LBP are conflicting and heterogeneous. Furthermore, there are only few studies on the association between body sway and LBP. METHODS: The subjects
(n = 874) belonged to a subcohort of the Northern Finland Birth Cohort 1986 (mean age 19 years). Trunk muscle strength and body sway were measured from all subjects. LBP symptoms were inquired with a questionnaire, which was completed
concurrently with the examinations. Latent Class Analysis (LCA) was used to cluster the subjects according to their LBP symptoms. RESULTS: LCA analysis produced 6 clusters differing with respect to LBP symptoms. There were no
statistically significant differences between the clusters in trunk muscle strength or body sway. CONCLUSION: LBP does not seem to be associated with maximal isometric trunk muscle strength or body sway in young adults.


05/2005: After 10 years, patients of whom underwent back surgery were in slightly less pain that patients who refused surgery.

Here's some more analysis from the famous "Maine Lumbar Spine Study."  It would seem that after a statistically reliable 10-year follow-up period, patients who underwent back surgery as a result of severe lower back pain and sciatica, did a little bit better with regard to pain when compared to patients who chose not to have surgery.  That is, 69% vs. 61% in the "some improvement" category; and 56% vs. 40% in the "much better or completely better" category.  Interestingly, 25% of both the surgically and non-surgically treated patients succumb to an addition back surgery (or succumb to a first back surgery for the patients who were initially un-operated upon) during that 10-year follow-up.  With regard to work and disability, however, there were no real differences between the groups.  Here’s the study:

Atlas SJ, Keller RB, Wu YA, Deyo RA, Singer DE. "Long-term outcomes of surgical and nonsurgical management of sciatica secondary to a lumbar disc herniation: 10 year results from the maine lumbar spine study." Spine. 2005 Apr 15;30(8):927-35.

General Medicine Division and the Clinical Epidemiology Unit, Medical Services,
Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
satlas@partners.org

STUDY DESIGN: A prospective cohort study. OBJECTIVE: To assess 10-year outcomes of patients with sciatica resulting from a lumbar disc herniation treated surgically or nonsurgically. SUMMARY OF BACKGROUND DATA: There is little
information comparing long-term outcomes of surgical and conservative therapy of lumbar disc herniation in contemporary clinical practice. Prior studies suggest that these outcomes are similar. METHODS: Patients recruited from the practices
of orthopedic surgeons, neurosurgeons, and occupational medicine physicians throughout Maine had baseline interviews with follow-up questionnaires mailed at  regular intervals over 10 years. Clinical data were obtained at baseline from a
physician questionnaire. Primary analyses were based on initial treatment received, either surgical or nonsurgical. Secondary analyses examined actual treatments received by 10 years. Outcomes included patient-reported symptoms of
leg and back pain, functional status, satisfaction, and work and disability compensation status.

RESULTS: Of 507 eligible consenting patients initially enrolled, 10-year outcomes were available for 400 of 477 (84%) surviving patients; 217 of 255 (85%) treated surgically, and 183 of 222 (82%) treated nonsurgically. Patients undergoing surgery had worse baseline symptoms and functional status than those initially treated nonsurgically. By 10 years, 25% of
surgical patients had undergone at least one additional lumbar spine operation, and 25% of nonsurgical patients had at least one lumbar spine operation. At 10-year follow-up, 69% of patients initially treated surgically reported
improvement in their predominant symptom (back or leg pain) versus 61% of those initially treated nonsurgically (P = 0.2). A larger proportion of surgical patients reported that their low back and leg pain were much better or completely gone (56% vs. 40%, P = 0.006) and were more satisfied with their current status (71% vs. 56%, P = 0.002). Treatment group differences persisted after adjustment  for other determinants of outcome in multivariate models. Change in the modified
Roland back-specific functional status scale favored surgical treatment, and the  relative benefit persisted over the follow-up period. Despite these differences, work and disability status at 10 years were comparable among those treated
surgically or nonsurgically.

CONCLUSIONS: Surgically treated patients with a herniated lumbar disc had more complete relief of leg pain and improved function  and satisfaction compared with nonsurgically treated patients over 10 years. Nevertheless, improvement in the patient's predominant symptom and work and disability outcomes were similar regardless of treatment received. For patients
in whom elective discectomy is a treatment option, an individualized treatment plan requires patients and their physicians to integrate clinical findings with patient preferences based on their symptoms and goals.

01/2007: The body's immune system may well be involved in the mechanism of sciatica:

The familiar names of Rydevik and Olmarker have once again caught my eye.  In this most instructive investigation, they, for the first time, have demonstrated that virgin nucleus pulposus (remember, the stuff inside the disc is normally hidden from the watchful immune system of the body) will turn on the bodies immune system when it's outside the disc. This supports the theory that when the disc ruptures and releases the virgin nucleus pulposus upon the adjacent sciatica nerve rootlet(s), the body “attacks” via an immune response—in some people, the attack may well be strong enogh to damage the nerve roots and cause sciatica (although this theory is yet to be fully proven).  here’s the article:

Geiss A, Larsson K, Rydevik B, Takahashi I, Olmarker K. "Autoimmune properties of nucleus pulposus: an experimental study in pigs." Spine. 2007 Jan 15;32(2):168-73.

Department of Orthopaedics, Sahlgrenska University Hospital, Göteborg University,Göteborg, Sweden.

STUDY DESIGN: Assessment of activated T and B cells in a subcutaneous chamber filled with autologous nucleus pulposus using flow cytometry and immunohistochemistry. OBJECTIVES: To examine if subcutaneously placed autologous
nucleus pulposus may attract activated T and B cells in an animal model. SUMMARY  OF BACKGROUND DATA: Nucleus pulposus has been suggested to trigger an autoimmune  response if exposed to the immune system, for example, in association with disc
herniation. T-cell activation represents a hallmark in the generation of an autoimmune response, subsequently leading to the differentiation of B cells, but  a causal association between the exposure of nucleus pulposus to the systemic circulation and T and B cell activation is still lacking. METHODS: Autologous nucleus pulposus was harvested from the intervertebral disc of 9 pigs and placed  subcutaneously in perforated titanium chambers. In order to control for the effect of the titanium chamber, an additional empty chamber was placed subcutaneously in each pig. After 7 days, the pigs were killed and the chambers were harvested. Flow cytometry and immunohistochemistry were used for analysis of T-helper cells (CD4+), cytotoxic T cells (CD8+), and B cells (Igkappa) in the chamber exudates and T cells (CD45RC) in the remaining blood clot tissue of the chamber.

RESULTS: As compared with the empty chambers, the proportion of activated T cells (CD4+ and CD8+) was significantly higher in the exudate of the  nucleus pulposus filled chamber. The proportion of activated B cells expressing immunoglobulin kappa (Igkappa) was also significantly elevated in the exudate of  the nucleus pulposus chambers. The analysis of the remaining chamber tissue revealed a significantly higher amount of T cells (CD45RC) in the nucleus pulposus chambers than in the empty chambers.

CONCLUSIONS: The present findings indicate that nucleus pulposus attracts activated T and B cells. However, since the cell population in the nucleus pulposus of young pigs may differ from that of adult humans, the obtained data may not be directly transferred to the human situation of a disc herniation. The observations in the present study may nevertheless explain some of the local tissue reactions occurring in association  with disc herniation and nerve root involvement, thereby providing further insight into the pathophysiology of sciatica

09/2008: Tumor Necrosis Factor - alpha (TNF-a) continues to be the number one suspect as a causative agent in radiculopathy:

The researchers found that in patients with sciatica (radiculopathy) the epidural fat (the fat that surrounds the inflammed nerve roots) is soaked with the biochemical TNF-a, which was found in very high in concentration when compared to the epidural fat from patients with pure discogenic pain (back pain without sciatica). Here's the abstract:

Genevay S, Finckh A, et al. "Elevated levels of tumor necrosis factor-alpha in periradicular fat tissue in patients with radiculopathy from herniated disc." Spine. 2008 Sep 1;33(19):2041-6.

Division of Rheumatology, University Hospitals of Geneva, Geneva, Switzerland.
stephane.genevay@hcuge.ch

STUDY DESIGN: Case-control study. OBJECTIVE: To determine whether inflammatory cytokines [tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and IL-8] are elevated in tissues intimately surrounding involved nerve roots of patients suffering from radiculopathy form herniated disc (HD). SUMMARY OF BACKGROUND DATA: Proinflammatory cytokines are postulated to play an important role in radiculopathy from HD. Although TNF-alpha has been found in human HD, it is not known whether TNF-alpha concentrations are increased in symptomatic patients. Epidural fat (EF) is another tissue in close contact with nerve roots.
Histologic modifications of EF have been reported in patients with sciatica but concentrations of inflammatory cytokines have never been studied. METHODS: Twenty-three lumbar HD along with adjacent EF (EFHD) were harvested from patients with radicular syndrome. As controls, 14 intervertebral discs (IVDs) and 10 samples of EF (EFC) were obtained from patients without radicular syndrome
undergoing spine surgery. Tissue explants were incubated ex vivo for 48 hours and the concentrations of cytokines were measured by elisa in the supernatants. Results were standardized according to tissue weight. RESULTS: All 4 cytokines were found at higher concentrations in EFHD compared with HD (P < 0.001). TNF-alpha was the only cytokine found in significantly higher levels in EFHD
compared with EFC [median, interquartile range 6.6, (1.6-16.3) pg/mL per milligram of tissue vs. 2.3 (1.3-5.0), P < 0.05] and to subcutaneous fat [0.35 (0-2.28), P < 0.001]. No significant increase of either cytokines was found in HD compared with IVD. CONCLUSION: Higher concentrations of TNF-alpha were found in EF from patients with radiculopathy from HD compared with patients suffering from other type of back pain. These results support the role of TNF-alpha in the pathogenesis of radiculopathy from HD.

06/2007: Disc to Disc Referred Pain! A small but interesting investigation.

Provocative discography, although not without controversy, continues to be the proverbial gold standard when it comes to deciding which disc(s) is bad and needs to be fused. That is, if the disc (during the discography procedure) re-creates your typical (concordant) pain upon injection/pressurization, then chances are that disc is a pain generator and needs to be fused.

Now, however, we have a small investigation that demonstrates that a bad disc (i.e., one that has a symptomatic annular tear) may "refer" pain to it's neighbor disc, which may not be a pain generator at all--so we gat a false positive upon pressurization of a good disc. This false positive may result in the surgeon opting to fuse a healthy disc.

Obviously, we need a bigger study, but this sure was interesting. Here's the study:

Arch Orthop Trauma Surg. 2007 Jun 19; [Epub ahead of print] Discography: can pain in a morphologically normal disc be due to an adjacent abnormal disc? Derincek A, Mehbod A, Schellhas K, Pinto M, Transfeldt E. Twin Cities Spine Center, Minneapolis, MN, USA, aderincek@hotmail.com.

Symptomatic patients who had Magnetic Resonance Imaging findings of degenerative disc disease and who failed conservative treatment were identified. As a preoperative test, these patients underwent discography. The patients, who experienced pain with injection into a morphologically normal disc adjacent to a morphologically abnormal disc, were included in the study. These patients subsequently had repeat discograms, during which the adjacent abnormal disc was first anesthetized with 2% lidocaine and the discogram was repeated at the adjacent normal level. All patients were blinded as to the nature of the procedure. Nine patients were identified (7 males and 2 females). The average age was 46.5 years (32-68). Two patients had a previous L4-Sacrum anterior and posterior fusion while 2 patients had L5-Sacrum anterior and posterior fusions. These four patients had solid fusions on Computerized Tomography scan and had developed adjacent segment degeneration according to MRI. Overall, each patient underwent an average of four discograms, at the lowest mobile disc segments. All of the patients were found to have a painful but morphologically normal disc adjacent to a painful and morphologically abnormal disc. The morphologically abnormal disc was anesthetized and the discography repeated on the normal disc. Upon this repeat discography, none of the patients experience any pain. The authors recommend anesthetizing painful abnormal discs prior to discography of the adjacent discs. This technique may avoid unnecessary dismissal of patients from treatment because of an appropriate response to discography. The normal disc may be due to referred pain from an adjacent abnormal disc.

01/2006: Can a Leaking Annular Tear cause Radiculopathy (Sciatica) without physical compression of the root? Yes, according to this Investigation:

Pain. 2007 Jan;127(1-2):11-6. Epub 2006 Sep 8. Chemical radiculitis. Peng B, Wu W, Li Z, Guo J, Wang X. Department of Orthopaedics, General Hospital of Armed Police, 69 Yongding Road, 100039 Beijing, China. pengbaogan@163.com

The theory of chemical radiculitis had been put forward about 30 years ago, but as yet it has not been proved by clinical studies. The aim of the current studies was to determine whether the annular tear of a painful disc proved by discography is the cause of radiating leg pain (radiculopathy) in patients with discogenic low back pain. Forty-two patients with discogenic low back pain at single disc level with concomitant radiating leg pain were studied in order to analyse the relationship between site of annular tear and side of radiating leg pain. Electromyogram and motor nerve conduction velocity were monitored to examine nerve root injury. The current studies found that there was a significant positive correlation between the site of annular tear and the side of radiation pain. Abnormalities of electromyogram and reduction of motor nerve conduction velocity were found on the side of radiating leg pain. The studies indicated that leakage of chemical mediators or inflammatory cytokines, which are produced in the painful disc, into epidural space through annular tear could lead to injury to adjacent nerve roots, and it might constitute the primary pathophysiologic mechanism of radiating leg pain in patients with discogenic low back pain but with no disc herniation.

07/2007: Cervical Disc Herniation w/ Radiculopathy: Which method is best? ACD, ACDF, ACDFI? Surprisingly, it doesn't matter! (although the ACD developed kyphosis).

Neurosurgery. 2007 Jul;61(1):107-16; discussion 116-7. Discectomy versus discectomy with fusion versus discectomy with fusion and instrumentation: a prospective randomized study. Xie JC, Hurlbert RJ. University of Calgary Spine Program, Foothills Hospital and Medical Centre, Calgary, Canada. OBJECTIVE: The need for interbody fusion after anterior cervical discectomy for radiculopathy remains controversial. The purpose of this study was to assess clinical and radiographic outcomes in patients with cervical radiculopathy after discectomy without fusion (ACD), discectomy with intervertebral fusion (ACDF), and discectomy with intervertebral fusion and instrumentation (ACDFI). METHODS: Forty-two consecutive patients with cervical radiculopathy who failed medical management were randomized to one of three treatment groups: ACD, ACDF, or ACDFI. Indices including symptoms, work status, Short Form-36, McGill pain scores, and anteroposterior/lateral flexion/extension x-rays were obtained preoperatively and during the follow-up period. RESULTS: There were no inter-group differences observed during the 2-year follow-up period with respect to neck pain, interscapular pain, or arm pain (P > 0.05). Short Form-36 scores demonstrated a dramatic postoperative improvement followed by further gradual improvement in both physical and mental components as well as other subscale scores in all groups during the follow-up period (P < 0.05). Fusion occurred in 67% of the ACD patients compared with 93% of the ACDF patients and 100% of the ACDFI patients (P < 0.05). Segmental kyphosis was noted in 75% of the ACD patients postoperatively compared with 17% preoperatively. There was no change in sagittal balance in the ACDF or ACDFI groups (P > 0.05). CONCLUSION: Patient selection and surgical decompression remain the key to achieving desirable clinical outcomes after cervical discectomy for radiculopathy. Within a 2-year follow-up period, the technique of reconstruction plays no role in clinical results. However, ACD alone results in segmental kyphosis compared with ACDF and ACDFI. PMID: 17621025 [PubMed - indexed for MEDLINE] Related Links

08/2002: Percutaneous Discectomy Methods (aka, minimally invasive) are NOT recommended by Johns Hopkins:

I've finally found a good investigation to support my contention that until Percutaneous Discectomy Methods are proven via randomized controlled trials, they should be avoided--traditional microdiscectomy is still the king!

Phys Med Rehabil Clin N Am. 2002 Aug;13(3):735-59.

Surgical management of cervical and lumbosacral radiculopathies: indications and outcomes. Storm PB, Chou D, Tamargo RJ. Department of Neurological Surgery, Johns Hopkins University School of Medicine, 725 North Wolfe Street, 817 Hunterian Boulevard, Baltimore, MD 21205, USA.

The most common indication for the surgical management of compressive cervical and lumbar radiculopathies is a herniated disc in a patient who has not improved with conservative management. Even though a herniated disk is a common condition, it is paramount that the examining physician considers an extensive differential diagnosis when evaluating radiculopathies, especially in patients with a history of cancer, multiple medical illnesses, secondary gain, or advanced age. This consideration has become even more important as imaging studies have improved, because previously undetected degenerative changes are now clearly visualized on MRI and CT scans. These improved studies, however, do not replace a thorough history and physical examination, because a patient's signs and symptoms may not correlate with the radiographic findings. The authors have presented a series of surgical techniques used to manage cervical and lumbar discectomies to the most recent "minimally invasive" percutaneous techniques. Much debate and controversy surround these more recent techniques. There is no controversy, however, in stating that achieving good outcomes, regardless of technique, is predicated on proper patient selection. Because patient selection is the most important predictor of outcome and because serious complications have been reported with "minimally invasive" percutaneous procedures, the authors continue to advocate the proven traditional surgical approaches until prospective, randomized studies demonstrate a clear benefit to using alternative techniques.

07/2007: Cochrane Review--2007--barely supports discectomy for disc herniation induced sciatica and does not support percutaneous (i.e., minimally invasive) discectomy.

Here's what Gibson and Waddell have to say after reviewing all the investigations on the subject:

CONCLUSION.: Surgical discectomy for carefully selected patients with sciatica due to lumbar disc prolapse provides faster relief from the acute attack than conservative management, although any positive or negative effects on the lifetime natural history of the underlying disc disease are still unclear. The evidence for other minimally invasive techniques remains unclear except for chemonucleolysis using chymopapain, which is no longer widely available.[Spine. 2007 Jul 15;32(16):1735-47]

07-01-07: Chromosome 21 may carry a gene for predisposition of lumbar disc herniation and sciatica.

J. Bone Miner. Res. 2007 May;22(5):701-7. Putative susceptibility locus on chromosome 21q for lumbar disc disease (LDD) in the Finnish population. Virtanen IM, Noponen N, Barral S, Karppinen J, Li H, Vuoristo M, Niinimäki J, Ott J, Ala-Kokko L, Männikkö M. Collagen Research Unit, Biocenter and Department of Medical Biochemistry and Molecular Biology, University of Oulu, Oulu, Finland. In the first linkage study on LDD, a common musculoskeletal disorder, a genome-wide scan was performed on 14 Finnish families. The analysis resulted in identification of a putative susceptibility locus for the disease on chromosome 21. INTRODUCTION: Lumbar disc disease (LDD) is a common musculoskeletal disorder that affects approximately 5% of the adult population. Several predisposing genetic and environmental risk factors have been identified for symptomatic LDD (i.e., symptomatic disc herniation and/or sciatic pain), but thus far, no common cause has been identified. MATERIALS AND METHODS: Medical history data were collected from 186 members of 14 Finnish families with LDD. RESULTS: A genome-wide scan resulted in 10 chromosomal regions providing LOD scores >1, and in fine mapping, maximum two-point LOD scores of 2.71, 2.36, and 2.04 were obtained for chromosomes 21 (D21S1257), 4 (D4S399), and 6 (D6S294), respectively. A second fine mapping confirmed the susceptibility of chromosome 21 with a two-point LOD score of 2.06 (D21S1922). In addition, a significant association between LDD and SNP rs716195 was observed (p<0.001), and case-control analysis revealed pointwise significant differences with several markers. Interestingly, the locus for another spinal disorder, ossification of the posterior longitudinal ligament (OPLL), has been mapped to chromosome 21q, partially overlapping with our candidate region. Two candidate genes with aggrecanase activity, ADAMTS-1 and ADAMTS-5, were analyzed in the region, suggesting linkage, leading to the identification of 13 sequence variations. None of the variations were disease-causing, however, because they were observed equally in affected and healthy individuals. CONCLUSIONS: We report here on the first putative susceptibility locus for LDD in the Finnish population. The candidate region on chromosome 21q spans >5.5 cM and contains several interesting genes for further analysis.

03/2007: The Chinese have released the 5-year results of the first cervical human disc transplant...

Although any research coming out of China should be taken with a grain of salt, their efforts with this investigation must be applauded. Their government truly seems to understand the importance of science and does not hamstring their researchers as the good old USA does--to our detriment--secondary to politics. Five years ago, they implanted flash-frozen cervical intervertebral discs into five patients and report on the outcomes, which are reported as favorable. It would seem, however, that these new discs will eventually meet the same fate as the originals, since DDD is secondary to diminished blood flow through the endplates, which is something can not be repaired. Nevertheless, this is a great effort and may, someday, result in another treatment option for DDD.

Lancet. 2007 Mar 24;369(9566):993-9. Comment in: Lancet. 2007 Mar 24;369(9566):968-9. Intervertebral disc transplantation in the treatment of degenerative spine disease: a preliminary study. Ruan D, He Q, Ding Y, Hou L, Li J, Luk KD. Department of Orthopedic Surgery, The Navy General Hospital, Beijing, China. BACKGROUND: Spinal fusion can be complicated by accelerated degeneration of the adjacent segments. Artificial disc replacements have been developed, but results are variable. Successful transplantations of intervertebral disc autografts, fresh allografts, and fresh-frozen allografts-ie, a non-fusion strategy-in which the mobility and stability of the spinal segment were preserved have been done in a primate model. Our aim was to determine the feasibility, safety, and long-term clinical results of disc transplantation in human beings. METHODS: Five patients, average age 47 years, with cervical disc herniation underwent transplantation of fresh-frozen composite disc allografts after disc excision. Serial MRI and static and dynamic radiographs were used to monitor the status of the grafts and the sagittal stability and mobility of the segment. FINDINGS: Good union of the graft endplates was seen by the end of 3 months after surgery in all patients. At a minimum follow-up of 5 years, the neurological symptoms of all patients had improved from before surgery levels. No immunoreaction was encountered. There was no olisthesis and only mild degenerative changes of the transplanted discs. All except one of the discs showed preservation of 7.0-11.3 degrees of sagittal motion at the final follow-up. MRI at 5 years showed preservation of hydration in at least two discs. INTERPRETATION: Despite signs of mild disc degeneration, the motion and stability of the spinal unit was preserved after transplantation of fresh-frozen allogenic intervertebral discs in our patients. With further refinements, such transplantations could be an effective treatment for degenerative disc disease.

06/2005: X-Stop May help stenotic patients; however, the results of this study are less than stellar:

The co-inventor of X-Stop has in the past published the results of his randomized controlled investigation into the efficacy of X-stop (Spine. 2005 Jun 15;30(12):1351-8.) The results--a 73% patient satisfaction rate--were a little to good to be true for me and I was waiting for another investigation from a group that did not hold the patent for the procedure. Well, it's not a RCT, but it fairly high quality and was published in Spine: These Scotish researchers found that 54% of the patients reported "clinically significant improvement in their symptoms," but only 33% reported significant clinical improvement with regard to physical function. Still, when compared to the alternative--fusion--it's probably worth a try if you suffer from stenosis related claudication.

Spine. 2007 May 20;32(12):1345-8. One-year results of X Stop interspinous implant for the treatment of lumbar spinal stenosis. Siddiqui M, Smith FW, Wardlaw D. Department of Orthopaedics, Woodend Hospital, Aberdeen, Scotland, UK. manalsiddiquis@yahoo.co.uk STUDY DESIGN: Prospective observational study. OBJECTIVE: To prospectively assess the clinical outcome of patients with symptomatic lumbar spinal stenosis before and at periodic intervals after X Stop implantation and to compare the data with previous studies. SUMMARY OF BACKGROUND DATA: The X Stop Interspinous Process Distraction Device is a relatively new interspinous implant designed for patients with symptomatic spinal stenosis particularly neurogenic claudication. Previously, a randomized study has shown a 75% improvement in symptoms and physical function at 1-year post-X Stop implantation for lumbar spinal stenosis. The only other study is a preliminary report of only 10 patients with variable intervals of clinical outcome assessment. METHOD: Forty consecutive patients were enrolled and surgically treated with X Stop implantation. The X Stop device was implanted at the stenotic segment, which was either at 1 or 2 levels in each patient. They were clinically evaluated at the preoperative, 3-month, 6-month, and 1-year stage with clinical questionnaires (Zurich Claudication Questionnaire, Oswestry Disability Index, and SF-36). RESULTS: Sixteen patients failed to complete all the questionnaires at all time intervals and hence were excluded, leaving 24 patients who had completed all questionnaire at all time interval. By 12 months, 54% of these 24 patients reported clinically significant improvement in their symptoms, 33% reported clinically significant improvement in physical function, and 71% expressed satisfaction with the procedure. 29% of the patients required caudal epidural after 12 months after surgery for recurrence of their symptoms of neurogenic claudication. CONCLUSION: The results of this prospective observational study indicate that X Stop offers significant short-term improvement over a 1-year period. It is a safe, effective, and less invasive alternative for treatment of lumbar spinal stenosis. Our results, however, are less favorable than the previous multicenter, randomized study.

03/2007: Degenerated Facet Joints may leak cytokines onto the posterior nerve roots and create symptoms of leg pain.

J Orthop Sci. 2007 Mar;12(2):154-60. Epub 2007 Mar 30. Correlation between inflammatory cytokines released from the lumbar facet joint tissue and symptoms in degenerative lumbar spinal disorders. Igarashi A, Kikuchi S, Konno S. Department of Orthopedic Surgery, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima 960-1295, Japan.

BACKGROUND: Lumbar facet joint tissue has inflammatory cytokines. However, no reports have shown whether inflammatory cytokines in the facet joint leads to pain. This study was designed to characterize the correlation between inflammatory cytokines released from facet joint tissue and symptoms in degenerative lumbar spinal disorders. The purpose of this study was to seek involvement of inflammatory facet joint for radiculopathy in lumbar spinal canal stenosis with clinical and anatomical studies. METHODS: Lumbar facet joint cartilage and synovial tissues in 40 cases of posterior lumbar surgery were harvested to measure tumor necrotizing factor-alpha (TNFalpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) during operation. The visual analogue scale (VAS) and Roland-Morris disability questionnaire (RDQ) were used to examine the correlation between cytokine concentration and symptoms. Coloring agent was injected into facet joints of fresh cadavers to find leakage of pigment from the facet joint into the spinal canal. RESULTS: Inflammatory cytokines were detected in the joint tissues in the lumbar spinal canal stenosis (LSCS) and lumbar disc herniation (LDH) groups. A positive reaction rate of IL-1beta was significantly higher in the LSCS group than in the LDH group. IL-1beta-positive cases in the LSCS group showed higher VAS scores for leg pain and higher RDQ scores. Intraspinal canal tissues including lumbar nerve root were stained by injection of methylene blue into the facet joints. CONCLUSIONS: IL-1beta in facet joint cartilage in LSCS was associated with leg pain and a decline of quality of life. Inflammatory cytokines produced in degenerated facet joint may leak into the intraspinal space through the lateral part of the ventral facet joint capsule. These results suggest the involvement of inflammatory cytokines in degenerated lumbar facet joints regarding the genesis of pain production.

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