The Science. The Research.
Clinical Studies
Abstract
Objective
Assess the safety and efficacy of intradiscal fibrin sealant in adults with chronic discogenic low back pain.
Design
Prospective, FDA approved pilot study. This study limits treatment to one or two discs regardless of MRI findings. This study allows fibrin injection only into the center nucleus pulposus, and not the outer annulus fibrosus tears. This study utilizes low-specificity discography for pre-treatment diagnosis, because high-specificity annulograms are performed by fewer physicians
Setting
Three tertiary spine centers in the United States.
Subjects
Fifteen adults with chronic, single, or contiguous two‐level lumbar discogenic pain confirmed through discography.
Interventions
Delivery of Fibrin Sealant into symptomatic lumbar disc center nucleus pulposus, and not disc outer annulus fibrosis tears.
Outcome Measures
Assessments were performed at pre-treatment baseline, 72 hours, and week 1, 4, 13, 26, 52, and 104 following treatment. Potential adverse events were evaluated with serial assessment of neurological status, and plain film radiograph, and magnetic resonance imaging (MRI). Efficacy measures included serial Visual Analog Scale (VAS) measurements and the Roland‐Morris Disability Questionnaire (RMDQ).
Results
Safety was demonstrated, with no significant adverse events. Two patients reported self-resolved muscle spasm. X‐ray and MRI demonstrated no adverse changes. One subject (Johns Hopkins site) experienced discitis, and needle aspiration identified normal oral flora, determined to be resultant of concurrent dental procedure, and resolved with antibiotics.
Efficacy
Mean low back pain VAS scores improved from 72.4 (95% c.i. 64.6–80.3) at baseline to 31.7 (17.4–46.1), 35.4 (17.7–53.1), and 33.0 (16.3–49.6).
Function, measured by RMDQ, improved from 15.2 (12.7–17.7) at baseline to 8.9 (5.3–12.5), 6.2 (3.4–9.1), and 5.6 (2.9‐8.4) at 26, 52, and 104 weeks, respectively.
Conclusion
Intradiscal fibrin sealant injection demonstrates safety and efficacy, and provides statistically significant improvement in pain and function. Further research could evaluate likelihood of improving outcomes further through: (a) utilizing more specific diagnostic annulograms instead of discograms; (b) treating every disc with annular tears instead of only one or two; and (c) injecting fibrin directly into annulus fibrosus tears to optimize disc’s containment of nucleus pulposus gel while minimizing its outward displacement.
Publications
Abstract
Background context
Intradiscal electrothermal therapy (IDET) is a treatment for discogenic low back pain the efficacy of which has not been rigorously tested.
Purpose
To compare the efficacy of IDET with that of a placebo treatment.
Study design/setting
Randomized, placebo-controlled, prospective trial.
Patient sample
Patients were recruited by referral and the media. No inducements were provided to any patient in order to have them participate. Of 1,360 individuals who were prepared to submit to randomization, 260 were found potentially eligible after clinical examination and 64 became eligible after discography. All had discogenic low back pain lasting longer than 6 months, with no comorbidity. Thirty-seven were allocated to IDET and 27 to sham treatment. Both groups were satisfactorily matched for demographic and clinical features.
Methods
IDET was performed using a standard protocol, in which the posterior annulus of the painful disc was heated to 90 C. Sham therapy consisted of introducing a needle onto the disc and exposing the patient to the same visual and auditory environment as for a real procedure. Thirty-two (85%) of the patients randomized to the IDET group and 24 (89%) of those assigned to the sham group complied fully with the protocol of the study, and complete follow-up data are available for all of these patients.
Outcome measures
The principal outcome measures were pain and disability, assessed using a visual analog scale for pain, the Short Form (SF)-36, and the Oswestry disability scale.
Results
Patients in both groups exhibited improvements, but mean improvements in pain, disability and depression were significantly greater in the group treated with IDET. More patients deteriorated when subjected to sham treatment, whereas a greater proportion showed improvements in pain when treated with IDET. The number needed to treat, to achieve 75% relief of pain, was five. Whereas approximately 40% of the patients achieved greater than 50% relief of their pain, approximately 50% of the patients experienced no appreciable benefit.
Conclusions
Nonspecific factors associated with the procedure account for a proportion of the apparent efficacy of IDET, but its efficacy cannot be attributed wholly to a placebo effect. The results of this trial cannot be generalized to patients who do not fit the strict inclusion criteria of this study, but IDET appears to provide worthwhile relief in a small proportion of strictly defined patients undergoing this treatment for intractable low back pain.
NASS Outstanding Paper
RANDOMISED, PLACEBO-CONTROLLED TRIAL OF INTRADISCAL ELECTROTHERMAL THERAPY FOR CHRONIC LOW BACK PAIN · Kevin Pauza, Simon Howell, +4 authors Nikolai Bogduk
· Medicine
· 2003 (1 March 2003)
INTRODUCTION: Intradiscal electrothermal therapy (IDET) is a controversial, new treatment for low back pain, whose efficacy has not been tested in randomised trials. The present study was undertaken to compare the efficacy of IDET with that of a placebo treatment. METHODS: Patients were recruited by referral and by advertising in the media. Of 4,530 individuals who enquired, 1,360 were prepared to submit to randomisation. Of these, 260 were found potentially eligible after clinical examination, and 64 became eligible after discography. All had discogenic low back pain lasting longer than six months, with no co-morbidity. Thirty-seven were allocated to IDET, and 27 to sham therapy. Both groups were satisfactorily matched for demographic and clinical features. IDET was performed using a standard protocol, in which the posterior annulus of the painful disc was heated to 90°C. Sham therapy consisted of introducing a needle on to the disc and exposing the patient to the same visual and auditory environment as for a real procedure. Follow-up at six months was achieved in over 85% of patients. Pain and disability were assessed using a visual analog scale for pain, the SF-36, the Oswestry disability scale, and the Back Depression Inventory. RESULTS: Patients in both groups exhibited improvements, but improvements in pain, disability, and depression, were significantly greater in the group treated with IDET. Pain scores improved by 24 points in the IDET group compared with 11 in the sham group. Oswestry scores improved by 11 in the IDET group, but only by four in the sham group. More patients deteriorated when subjected to sham treatment, whereas eight patients (25%) achieved greater than 75% relief of pain following IDET. Only one patient did so after sham treatment. The number needed to treat, to achieve 75% relief of pain, was five. No patient suffered any adverse effects. DISCUSSION: IDET fails to provide relief in some 50% of patients. Consequently, its efficacy is difficult to demonstrate statistically. Nevertheless, IDET provides satisfying relief in a substantial proportion of patients. Non-specific factors account for a large proportion of the apparent efficacy of IDET, but its efficacy cannot be attributed wholly to a placebo effect. The efficacy of IDET may be related critically to patient selection and the technique used. Improvements in either of these areas may improve the effect-size of IDET. Meanwhile, IDET is a low risk procedure that constitutes a legitimate option for patients with discogenic low back pain whose only alternative is fusion.
Abstract
Background context
In a small prospective study assessing 10 symptomatic and 10 asymptomatic subjects, Schellhas et al. compared cervical discography to magnetic resonance imaging. Within that study he reported on the distribution of pain for the C3–C4 to C6–C7 levels. Four years later, Grubb and Ellis reported retrospective data from his 12-year experience using cervical discography from C2–C3 to C7–T1 in 173 patients. To date, no large prospective study defining pain referral patterns for each cervical disc has been performed.
Purpose
To conduct a prospective visual and statistical descriptive study of pain provocation of a cohort of subjects undergoing cervical discography.
Study design/setting
Prospective multicenter descriptive study.
Methods
Pain referral maps were generated for each disc level from patients undergoing cervical discography with at least two levels assessed. If concordant pain was reproduced in a morphologically abnormal disc, the subject immediately completed a pain diagram. An independent observer interviewed the subject and recorded the location of provoked symptoms. Visual data were compiled using a body sector bit map, which consisted of 48 clinically relevant body regions. Visual maps with graduated color codes and frequencies of symptom location at each cervical disc level were generated.
Results
A total of 101 symptom provocation maps were recorded during cervical discography on 41 subjects. There were10 at C2–C3, 19 at C3–C4, 27 at C4–C5, 27 at C5–C6, 16 at C6–C7 and 2 at C7–T1. Predominantly unilateral symptoms were provoked just as often as bilateral symptoms. The C2–C3 disc referred pain to the neck, subocciput and face. The C3–C4 disc referred pain to the neck, subocciput, trapezius, anterior neck, face, shoulder, interscapular and limb. The C4–C5 disc referred pain to the neck, shoulder, interscapular, trapezius, extremity, face, chest and subocciput. The C5–C6 disc referred pain to the neck, trapezius, interscapular, suboccipital, anterior neck, chest and face. The C6–C7 disc referred pain to the neck, interscapular, trapezius, shoulder, extremity and subocciput. At C7–T1 we produced neck and interscapular pain. Visual maps with graduated color codes and frequencies of symptom location at each cervical disc level were generated.
Conclusions
In conclusion, these results confirm the observations of prior investigators that cervical internal disc disruption can elicit axial and peripheral symptoms. The particular patterns of pain generation allow the discographer to preprocedurally anticipate disc levels to assess. With these data, the number of disc punctures that are required can be limited rather than routinely assessing all cervical discs.
NASS Outstanding Paper
Spine (Phila Pa 1976). 2011 Aug 15;36(18):E1201-9. doi: 10.1097/BRS.0b013e31820566b2.
Biological and biomechanical effects of fibrin injection into porcine intervertebral discs. Buser Z1, Kuelling F, Liu J, Liebenberg E, Thorne KJ, Coughlin D, Lotz JC.
Abstract
STUDY DESIGN:
Surgically denucleated porcine intervertebral discs (IVD) were injected with BIOSTAT BIOLOGX Fibrin Sealant (FS), and the in vivo effects were assessed over time by histological, biochemical, and mechanical criteria.
OBJECTIVE:
The objectives were to test whether the intradiscal injection of FS stimulates disc healing.
SUMMARY OF BACKGROUND DATA:
Disc avascularity prevents the deposition of a provisional fibrin scaffold that typically facilitates soft tissue repair. Poor disc wound healing leads to disc damage accumulation and chronic inflammation characterized by overproduction of proinflammatory cytokines and proteolytic enzymes.
METHODS:
Four lumbar IVDs from each of 31 Yucatan minipigs were randomized to untreated controls; degenerative injury (nucleotomy); and nucleotomy plus FS injection. Animals were killed at 1, 2, 3, 6, and 12 weeks postsurgery. IVDs were harvested to quantify (1) architecture using morphological and histological grading; (2) proteoglycan composition using DMMB assay; (3) cytokine content using ELISA; and (4) mechanical properties using quantitative pressure/volume testing.
RESULTS:
There was progressive invasion of annular tissue into the nucleus of nucleotomy discs and concomitant reduction in proteoglycan content. By contrast, FS supplementation inhibited nuclear fibrosis and facilitated proteoglycan content recovery over time. FS discs synthesized significantly less TNF-α than degenerate discs (66% vs. 226%, P < 0.05) and had upregulation of IL-4 (310% vs. 166%) and TGF-β (400% vs. 117%) at 2 to 3 weeks posttreatment. At the third week postsurgery, the denucleated discs were less stiff than controls (pressure modulus 779.9 psi vs. 2754.8 psi; P < 0.05) and failed at lower pressures
(250.5 psi vs. 492.5 psi; P < 0.05). The stiffness and leakage pressure of the FS-treated discs recovered to control values after 6 and 12 weeks, respectively.
CONCLUSION:
FS facilitated structural, compositional, and mechanical repair of the surgically damage
Abstract
STUDY DESIGN:
This prospective study evaluated the diagnostic utility of historically accepted sacroiliac joint tests. A multidisciplinary expert panel recommended 12 of the “best” sacroiliac joint tests to be evaluated against a criterion standard of unequivocal gain relief after an intra-articular injection of local anesthetic into the sacroiliac joint.
OBJECTIVES:
To identify a single sacroiliac joint test or ensemble of test that are sufficiently useful in diagnosing sacroiliac joint disorders to be clinically valuable.
SUMMARY OF BACKGROUND DATA:
No previous research has been done to evaluate any physical test of sacroiliac joint pain against an accepted criterion standard.
METHODS:
Historical data was obtained, and the 12 tests were performed by two examiners on 85 patients who subsequently underwent sacroiliac joint blocks. Ninety percent or more relief was considered a positive response, and less then 90% relief was considered a negative response.
RESULTS:
There were 45 positive and 40 negative responses. No historical feature, none of the 12 sacroiliac joint tests, and no ensemble of these 12 tests demonstrated worthwhile diagnostic value.
CONCLUSION:
Sacroiliac joint pain is resistant to identification by the historical and physical examination data from tests evaluated in this study.
Pauza K, Wright C, Fairbourn A. Techniques of Regional Anesthesia and Pain Management.
Treatment of annular disc tears and “leaky disc syndrome” with fibrin sealant.2015; 19(1-2):45-49.
Treatment of annular disc tears and
“leaky disc syndrome” with fibrin sealant
Abstract The surfaces of annulus fibrosus tears are known harbingers of inflammatory constituents within intervertebral discs, stimulating sensitized nocioceptors within those tears. Other current treatment options of internal disc disruption neglect to specifically address the surface of these tears. Therefore, this investigation answers the question: does nonautologous fibrin sealant applied to the surface of annulus fibrosus tears mechanically glue and seal annular tears? Regarding this query, results suggest nonautologous concentrated fibrin successfully seals annulus fibrosus tears with a “suture-like mechanical sealant,” serving as a safe option for treating symptomatic or nonsymptomatic intervertebral disc tears. Sealing tears prevents pain-generating chemicals of the nucleus pulposus from leaking through annular tears. More specifically, fibrin sealant minimizes or eliminates extravasation of nucleus pulposus through tears and voids within the annulus fibrosus. Moreover, an investigation subjecting discs to an “internal pressure challenge” objectively affirms fibrin׳s ability to seal torn and degenerated discs against a pressure challenge. (1 psi = 6.89476 kPs (disc mean pressure pretreatment = 75.84 kPs; post-treatment = 179.3 kPs: (n = 347, P < 0.001). Therefore, sealing annular tears serves to minimize extravasation of nucleus pulposus through annular tears, thus potentially treating symptoms caused by internal disc disruption, “Leaky Disc Syndrome,” and chemical radiculopathy. Additionally, sealing annular tears potentially allows adjunctive regenerative biologics such as mesenchymal precursor cells, platelet rich plasma, and growth factors to remain within discs, thus, potentially optimizing their efficacy. A prior in vivo investigation demonstrated the vast majority of mesenchymal stem cells leaked from animal intravertebral discs, and another demonstrated radiolabeled mesenchymal stem cells leaked from degenerated discs and were subsequently found within new exuberant osteophytes adjacent to the degenerated disc. Intra-annular nonautologous concentrated fibrin shares a benefit of other intradiscal biologics in that fibrin does not cause aberrant detrimental mechanical forces on adjacent discs, compared with surgical fusion and disc arthrodesis, which
both cause aberrant, potentially damaging mechanical forces on adjacent segments. The mean number of morphologically abnormal lumbar intervertebral discs in this population with chronic low back pain was 3.21 discs.
