Correlation of pain with objective quantification of magnetic resonance images in older adults with chronic low back pain.

STUDY DESIGN: Cross sectional study. OBJECTIVE: The goal of this study is to identify relationships between objectively measured and subjectively scored parameters and reported pain. SUMMARY OF BACKGROUND DATA: Studies have demonstrated the unreliability of magnetic resonance imaging (MRI)-based parameters to identify pathological pain generators of chronic low back pain, but they were based on visual inspection and subjective assessment of lumbar disc features. Advancements in computer image analysis provide objective measurements of lumbar disc features. METHODS: Two radiologists evaluated 39 axial and sagittal T1- and T2-weighted MR images of patients with chronic axial low back pain (age, >65 yr) and graded 4 subjective lumbar disc parameters (T2 signal intensity, nucleus shape, Modic changes, and osteophyte formation) whose sum is the cumulative MRI score. Objective parameter, MRI index, was calculated as the product of the measured lumbar disc area and total disc MRI signal intensity. Discs were sorted from least to the most degenerated relative to each parameter. Pearson correlation coefficient and multiple linear regression analysis were performed between the reported pain score and each parameter. RESULTS: The most and least degenerated discs in each patient, as assessed by MRI index, had the highest negative and positive correlation coefficient and regression weight contribution, respectively. All subjective parameters had low correlation coefficients and regression goodness of fit. CONCLUSION: Although limited by small sample size, the objective parameter, MRI index, can be a potential imaging biomarker used to identify possible pain generators. This study presents a potential new application of MR imaging in identifying pain generators of patients with chronic low back pain.

Injection of human umbilical tissue-derived cells into the nucleus pulposus alters the course of intervertebral disc degeneration in vivo.

BACKGROUND CONTEXT: Patients often present to spine clinic with evidence of intervertebral disc degeneration (IDD). If conservative management fails, a safe and effective injection directly into the disc might be preferable to the risks and morbidity of surgery. PURPOSE: To determine whether injecting human umbilical tissue-derived cells (hUTC) into the nucleus pulposus (NP) might improve the course of IDD. DESIGN: Prospective, randomized, blinded placebo-controlled in vivo study. PATIENT SAMPLE: Skeletally mature New Zealand white rabbits. OUTCOME MEASURES: Degree of IDD based on magnetic resonance imaging (MRI), biomechanics, and histology. METHODS: Thirty skeletally mature New Zealand white rabbits were used in a previously validated rabbit annulotomy model for IDD. Discs L2-L3, L3-L4, and L4-L5 were surgically exposed and punctured to induce degeneration and then 3 weeks later the same discs were injected with hUTC with or without a hydrogel carrier. Serial MRIs obtained at 0, 3, 6, and 12 weeks were analyzed for evidence of degeneration qualitatively and quantitatively via NP area and MRI Index. The rabbits were sacrificed at 12 weeks and discs L4-L5 were analyzed histologically. The L3-L4 discs were fixed to a robotic arm and subjected to uniaxial compression, and viscoelastic displacement curves were generated. RESULTS: Qualitatively, the MRIs demonstrated no evidence of degeneration in the control group over the course of 12 weeks. The punctured group yielded MRIs with the evidence of disc height loss and darkening, suggestive of degeneration. The three treatment groups (cells alone, carrier alone, or cells+carrier) generated MRIs with less qualitative evidence of degeneration than the punctured group. MRI Index and area for the cell and the cell+carrier groups were significantly distinct from the punctured group at 12 weeks. The carrier group generated MRI data that fell between control and punctured values but failed to reach a statistically significant difference from the punctured values. There were no statistically significant MRI differences among the three treatment groups. The treated groups also demonstrated viscoelastic properties that were distinct from the control and punctured values, with the cell curve more similar to the punctured curve and the carrier curve and carrier+cells curve more similar to the control curve (although no creep differences achieved statistical significance). There was some histological evidence of improved cellularity and disc architecture in the treated discs compared with the punctured discs. CONCLUSIONS: Treatment of degenerating rabbit intervertebral discs with hUTC in a hydrogel carrier solution might help restore the MRI, histological, and biomechanical properties toward those of nondegenerated controls. Treatment with cells in saline or a hydrogel carrier devoid of cells also might help restore some imaging, architectural, and physical properties to the degenerating disc. These data support the potential use of therapeutic cells in the treatment of disc degeneration.

Injection of AAV2-BMP2 and AAV2-TIMP1 into the nucleus pulposus slows the course of intervertebral disc degeneration in an in vivo rabbit model.

BACKGROUND CONTEXT: Intervertebral disc degeneration (IDD) is a common cause of back pain. Patients who fail conservative management may face the morbidity of surgery. Alternative treatment modalities could have a significant impact on disease progression and patients' quality of life. PURPOSE: To determine if the injection of a virus vector carrying a therapeutic gene directly into the nucleus pulposus improves the course of IDD. STUDY DESIGN: Prospective randomized controlled animal study. METHODS: Thirty-four skeletally mature New Zealand white rabbits were used. In the treatment group, L2-L3, L3-L4, and L4-L5 discs were punctured in accordance with a previously validated rabbit annulotomy model for IDD and then subsequently treated with adeno-associated virus serotype 2 (AAV2) vector carrying genes for either bone morphogenetic protein 2 (BMP2) or tissue inhibitor of metalloproteinase 1 (TIMP1). A nonoperative control group, nonpunctured sham surgical group, and punctured control group were also evaluated. Serial magnetic resonance imaging (MRI) studies at 0, 6, and 12 weeks were obtained, and a validated MRI analysis program was used to quantify degeneration. The rabbits were sacrificed at 12 weeks, and L4-L5 discs were analyzed histologically. Viscoelastic properties of the L3-L4 discs were analyzed using uniaxial load-normalized displacement testing. Creep curves were mathematically modeled according to a previously validated two-phase exponential model. Serum samples obtained at 0, 6, and 12 weeks were assayed for biochemical evidence of degeneration. RESULTS: The punctured group demonstrated MRI and histologic evidence of degeneration as expected. The treatment groups demonstrated less MRI and histologic evidence of degeneration than the punctured group. The serum biochemical marker C-telopeptide of collagen type II increased rapidly in the punctured group, but the treated groups returned to control values by 12 weeks. The treatment groups demonstrated several viscoelastic properties that were distinct from control and punctured values. CONCLUSIONS: Treatment of punctured rabbit intervertebral discs with AAV2-BMP2 or AAV2-TIMP1 helps delay degenerative changes, as seen on MRI, histologic sampling, serum biochemical analysis, and biomechanical testing. Although data from animal models should be extrapolated to the human condition with caution, this study supports the potential use of gene therapy for the treatment of IDD.

In vivo analysis of cervical range of motion after 4- and 5-level subaxial cervical spine fusion.

STUDY DESIGN: A cohort study analyzing the cervical range of motion (ROM) of subjects with 4- or 5-level posterior laminectomy and fusion or anterior and posterior decompression and fusion operation. OBJECTIVE: The purpose of this study was to evaluate the effect of extending a C3-C7 fusion to C3-T1 on subject's ROM and level of disability. SUMMARY OF BACKGROUND DATA: Cadaveric studies show a reduction in the ROM of C3-C7 cervical fusion spines. In vivo, surgeons treat symptomatic cervical subaxial spine with either a C3-C7 fusion or C3-T1 fusion. While in some cases extending the fusion level to T1 is merited due to pathology, most cases are due to surgeon's preference to avoid future degeneration and reoperation of the C7-T1 junction. METHODS: This study involved 44 4-level fusion and 20 5-level fusion subjects along with 18 nonoperative controls. Operative subjects were divided according to early or late postoperative clinical visit. Subjects were asked to complete the neck disability index survey and their maximum ROM during flexion/extension, axial rotation, and lateral bending was measured using a virtual reality assisted electromagnetic tracking system. In addition, the helical axis of motion was calculated for flexion and extension motions. An analysis of variance statistical test was used to determine significant differences between study groups. RESULTS: Five- level subjects had significantly less ROM than 4-level subjects and both groups were significantly less than control group during all motions. There was no effect of postoperative time on subject's ROM. In addition, there was no difference in the center of helical axis of rotation across the 3 groups. Finally, both operative groups exhibited similar levels of mild disability as measured by the neck disability index. CONCLUSIONS: Extending the subaxial fusion from C3-C7 to include C7-T1 resulted in a significant loss of ROM, while postoperative time healing, center of rotation, and level of disability were similar across groups. This finding merits further investigation of the intersegmental motions of the cervical spine.

Influence of number of operated levels and postoperative time on active range of motion following anterior cervical decompression and fusion procedures.

STUDY DESIGN: A cohort study analyzing the cervical range of motion of subjects with anterior cervical decompression and fusion operation (ACDF). OBJECTIVE: The purpose of this study was to compare the cervical range of motion of subjects who underwent an ACDF operation to age-matched healthy nonoperative subjects. Subjects were divided according to the number of operated levels, postoperative time point, and level of disability. SUMMARY OF BACKGROUND DATA: ACDF is an operative treatment aimed at expansion of the spinal canal and relief of cord compression. In addition to alleviating pain, 2 common tools are used to measure postoperative success; cervical range of motion kinematic analysis and subjective evaluation questionnaires (Neck Disability Index [NDI]). METHODS: This study involved 25 preoperative and 110 postoperative ACDF subjects as well as 18 control volunteers with no prior history of neck complaints. ACDF subjects were divided according to the number of operated levels; 1-, 2-, 3-, and 4-levels as well as time of their clinical visit; preoperative, early, and late postoperative. Before kinematic testing, the subjects were asked to complete the NDI survey. A virtual reality assisted electromagnetic tracking was used to measure an active voluntary motion of the head relative to the torso. The subjects' maximum range of motion was calculated and compared as they executed 3 to 5 consecutive cycles of the primary motions, flexion/extension, axial rotation, and lateral bending. An analysis of variance statistical test (P < 0.01) was used to determine significant differences between study groups. RESULTS.: Subject's range of motion decreased relative to control as the number of operated levels increased. Moreover, 1- and 2-level subjects increased their range motion relative to preoperative. Finally, there was a decrease in range of motion as the subject's level of disability increased as measured by an NDI score but all subjects reported a lower score relative to preoperative time point. CONCLUSION: The active range of motion of subjects who underwent an ACDF surgery increased postoperative and was dependent on the number of operated levels. In addition, there was an improvement in the disability level after the surgery as measured by the NDI score.

Matching the oculomotor drive during head-restrained and head-unrestrained gaze shifts in monkey.

High-frequency burst neurons in the pons provide the eye velocity command (equivalently, the primary oculomotor drive) to the abducens nucleus for generation of the horizontal component of both head-restrained (HR) and head-unrestrained (HU) gaze shifts. We sought to characterize how gaze and its eye-in-head component differ when an "identical" oculomotor drive is used to produce HR and HU movements. To address this objective, the activities of pontine burst neurons were recorded during horizontal HR and HU gaze shifts. The burst profile recorded on each HU trial was compared with the burst waveform of every HR trial obtained for the same neuron. The oculomotor drive was assumed to be comparable for the pair yielding the lowest root-mean-squared error. For matched pairs of HR and HU trials, the peak eye-in-head velocity was substantially smaller in the HU condition, and the reduction was usually greater than the peak head velocity of the HU trial. A time-varying attenuation index, defined as the difference in HR and HU eye velocity waveforms divided by head velocity [alpha = (H(hr) - E(hu))/H] was computed. The index was variable at the onset of the gaze shift, but it settled at values several times greater than 1. The index then decreased gradually during the movement and stabilized at 1 around the end of gaze shift. These results imply that substantial attenuation in eye velocity occurs, at least partially, downstream of the burst neurons. We speculate on the potential roles of burst-tonic neurons in the neural integrator and various cell types in the vestibular nuclei in mediating the attenuation in eye velocity in the presence of head movements.