Research news and notes

Nucleoplasty—how useful is it? 

Intradiscal “coblation” is a procedure involving localized radiofrequency heating and dissolution of tissue. It is also called “nucleoplasty” [2], [5]. It joins the ranks of disk-related procedures that remove or destroy part of the intervertebral disk in an attempt to control back pain. A recent study by Al-Zain et al [2] presents 1-year follow-up data on patients treated with nucleoplasty for “chronic discogenic low back pain.” A visual analogue pain scale was used, as well as details about analgesic consumption, disability, and ability to work. At the 12-month follow-up, 69 of the original 96 patients were evaluated. Others were unavailable for various reasons, including 11 excluded because they developed disk sequestration at the level of treatment or at another level. Of the 69 patients available, 58% reported decreased pain. The authors also report a significant reduction in analgesic consumption and improved ability to work. The results strike me as a bit weak; the actual failure rate and adverse events rate are hard to evaluate, and the benefit compared to best nonoperative care or natural history is not known. Nevertheless, the technology is finding applications beyond low back pain. Li et al [5] report good results using nucleoplasty for disk herniation in the cervical spine, in a retrospective uncontrolled case series of 126 consecutive patients.

Disk degeneration, as well as low back pain and neck pain, are very common. The natural history of these conditions is not well defined. As with many chronic illnesses, both spontaneous improvement and worsening occur over time. A clinical case series can present a new technique or open a discussion, but without any control or comparison group, even a multitude of reports do not answer key questions regarding the safety or efficacy of any new procedure. Hundreds of articles have been published about a variety of minimally invasive intradiscal procedures; only a few of those were randomized controlled trials (RCTs), and no RCT evaluated nucleoplasty with coblation [3]. Other minimally invasive methods for disk destruction did not do very well in RCTs [3].

Despite the continuing publication of new case series with reported success of various minimally invasive methods to lesion the intervertebral disk, many questions remain unanswered, and the use of the procedures remains in question. Are they different from placebo? Are they different from natural history of the disease? Are they better than current nonoperative treatment, such as physical therapy? What is the long-term effect? What is the risk and benefit of each procedure compared to current surgical options? The question of risks and adverse effects is also incompletely addressed by current literature. A smaller skin incision does not equal lesser risk of complications.

There is a great knowledge gap in our understanding of back pain, which invites a proliferation of methods to treat it, based on a variety of theories and empirical considerations. Ultimately, real solutions will come through real knowledge. Until then, we should be humble and prudent.

Cyclosporine A induces cardiac differentiation in mouse stem cells 

A recent study by Yan et al [6] in mouse embryonic stem cells demonstrated a drastic increase—10- to 20-fold, in the generation of cardiac progenitor cells and cardiomyocytes from mouse embryonic stem cells when those were exposed to cyclosporine A, an immunosuppressant. Why is this important? cyclosporine and tacrolimus (another immunosuppressant) are already known to have neuroprotective and neurotrophic effects [4]. The mechanism of action is not clear, but the effect of the drugs on the nervous system complicates the analysis of many studies of neural transplantation that involve allografts and xenografts. Immunosuppression with cyclosporine is administered to prevent graft rejection, especially across a species barrier. When a cell source is considered for transplantation into humans (ie, a human-derived cell line or embryonic stem cells), they are commonly tried first in an animal model, often rodents. The discovery of the effect of cyclosporine A on the differentiation of mouse stem cells further demonstrates the problem with rodent models for the study of neural transplantation in the context of xenografts and immunosuppression. It also demonstrates that what we do not know may be more important than we think. How do we know that the cells we grafted into the brain will not develop an affinity for the heart under the influence of cyclosporine A, migrate and lodge there? Are they doing so already, and we just have not looked for them outside the brain?

Antibiotics used to treat bone edema associated with a herniated lumbar disk 

Bone edema is often seen on magnetic resonance images next to the endplate, above and below a herniated or severely degenerated disk. This appearance is called Modic changes type I. Although bone edema can also be seen in infectious discitis, bone edema near the endplate is not typically thought to have infectious etiology. A trial of antibiotics as a treatment for back pain associated with Modic changes was recently reported by Albert et al [1]. In their study, they invited 37 patients with Modic changes and back pain who had participated in another study to enroll in a trial of Amoxicillin-clavulanate (500 mg/125 mg) 3× day for 90 days. Thirty-two patients enrolled, and 29 completed the trial. Three did not complete because they developed severe diarrhea. All patients were followed up at the completion of treatment and at a longer-term follow-up appointment (mean of 10.8 months). At every point in their follow-up, patients reported a highly significant improvement in all measured parameters: LBP intensity, number of days with pain, disease-specific and patient-specific function, and global perceived effect. These findings are sure to stir controversy. There were no controls, so placebo effect cannot be ruled out. The authors propose that infection may play a role in the causation of Modic changes in degenerative disk disease and after disk herniation. This idea remains a speculation and an unorthodox claim. Further study is necessary, but the report is intriguing enough that more research appears warranted. The authors propose a randomized controlled study. Such a study may supply evidence for or against the efficacy of antibiotics as a treatment for the symptoms of the patients who would participate; it cannot provide insight into the etiology of Modic changes and the reason why antibiotics may benefit the patients. However, culture and histopathological examination of the disk and the bone near the endplate through a radiologically guided needle biopsy can provide key information.