Louis G. Jenis

Prospective, randomized, multicenter Food and Drug Administration investigational device exemption study of lumbar total disc replacement with the CHARITÉ artificial disc versus lumbar fusion: Five-year follow-up

BACKGROUND CONTEXT The CHARITE artificial disc, a lumbar spinal arthroplasty device, was approved by the United States Food and Drug Administration in 2004 based on two-year safety and effectiveness data from a multicenter, prospective, randomized investigational device exemption (IDE) study. No long-term, randomized, prospective study on the CHARITE disc or any other artificial disc has been published to date. PURPOSE The purpose of this study was to compare the safety and effectiveness at the five-year follow-up time point of lumbar total disc replacement using the CHARITE artificial disc (DePuy Spine, Raynham, MA) with that of anterior lumbar interbody fusion (ALIF) with BAK cages and iliac crest autograft, for the treatment of single-level degenerative disc disease from L4 to S1, unresponsive to nonoperative treatment. STUDY DESIGN/SETTING Randomized controlled trial-five-year follow-up. PATIENT SAMPLE Ninety CHARITE patients and 43 BAK patients. OUTCOME MEASURES Self-reported measures: visual analog scale (VAS); validated Oswestry disability index (ODI version 1.0); Short-Form 36 Questionnaire, and patient satisfaction. Physiologic measures: radiographic range of motion, disc height, and segmental translation. Functional measures: work status. METHODS Of the 375 subjects enrolled in the CHARITE IDE trial, 277 were eligible for the five-year study and 160 patients thereof completed the five-year follow-up. The completers included 133 randomized patients. Overall success was defined as improvement> or =15 pts in ODI vs. baseline, no device failure, absence of major complications, and maintenance or improvement of neurological status. Additional clinical outcomes included an ODI questionnaire as well as VAS, SF-36, and patient satisfaction surveys. Work status was tracked for all patients. Safety assessments included occurrence and severity of adverse events and device failures. Radiographic analyses such as index- and adjacent-level range of motion, segmental translation, disc height, and longitudinal ossification were also carried out. RESULTS Overall success was 57.8% in the CHARITE group vs. 51.2% in the BAK group (Blackwelders test: p=0.0359, Delta=0.10). In addition, mean changes from baseline for ODI (CHARITE: -24.0 pts vs. BAK: -27.5 pts), VAS pain scores (CHARITE: -38.7 vs. BAK: -40.0), and SF-36 questionnaires (SF-36 Physical Component Scores [PCS]: CHARITE: 12.6 pts vs. BAK: 12.3 pts) were similar across groups. In patient satisfaction surveys, 78% of CHARITE patients were satisfied vs. 72% of BAK patients. A total of 65.6% patients in the CHARITE group vs. 46.5% patients in the BAK group were employed full-time. This difference was statistically significant (p=0.0403). Long-term disability was recorded for 8.0% of CHARITE patients and 20.9% of BAK patients, a difference that was also statistically significant (p=0.0441). Additional index-level surgery was performed in 7.7% of CHARITE patients and 16.3% of BAK patients. Radiographic findings included operative and adjacent-level range of motion (ROM), intervertebral disc height and segmental translation. At the five-year follow-up, the mean ROM at the index level was 6.0 degrees for CHARITE patients and 1.0 degrees for BAK patients. Changes in disc height were also similar for both CHARITE and BAK patients (0.7 mm for both groups, p=0.9827). Segmental translation was 0.4 and 0.8mm in patients implanted with CHARITE at L4-L5 vs. L5-S1, respectively, and 0.1mm in BAK patients. CONCLUSIONS The results of this five-year, prospective, randomized multicenter study are consistent with the two-year reports of noninferiority of CHARITE artificial disc vs. ALIF with BAK and iliac crest autograft. No statistical differences were found in clinical outcomes between groups. In addition, CHARITE patients reached a statistically greater rate of part- and full-time employment and a statistically lower rate of long-term disability, compared with BAK patients. Radiographically, the ROMs at index- and adjacent levels were not statistically different from those observed at two-years postsurgery.

Spine update: Lumbar foraminal stenosis

Lumbar foraminal stenosis is an important pathologic entity to identify in the patient being treated for radicular symptoms. This update reviews the anatomy, clinical presentation, neuroradiographic evaluation, and treatment of pathology located in the intervertebral foramen. Patients with significant leg pain refractory to conservative treatment and concordance between the demonstrated area of stenosis and radicular symptoms and signs are candidates for the decompressive procedures discussed. The role of arthrodesis and spinal instrumentation in the management of foraminal stenosis also is addressed.

Prospective study of iliac crest bone graft harvest site pain and morbidity

BACKGROUND CONTEXT Morbidity associated with autologous bone graft harvest is an important factor in determining the utility of expensive alternatives such as recombinant bone morphogenic protein. The most frequently reported complication associated with graft harvest is chronic pain. PURPOSE To prospectively determine the degree of pain and morbidity associated with autologous iliac crest bone graft harvest and its effect on activities of daily living. STUDY DESIGN Prospective observational cohort study. PATIENT SAMPLE One hundred ten adult patients undergoing elective posterior lumbar spinal fusion surgery involving autologous iliac crest bone graft harvest. OUTCOME MEASURES Patient self-reported Visual Analog Scale (VAS) scores for pain and a study-specific questionnaire regarding activities of daily living. METHODS One hundred ten patients were prospectively enrolled. Postoperative VAS scores (0-100) for harvest site pain were obtained at 6-week, 6- and 12-month follow-up. Patients completed a 12-month questionnaire regarding the persistence of specific symptoms and resulting limitation of specific activities. RESULTS One hundred four patients were available for 1-year follow-up. Mean VAS pain scores (scale 0-100) at 6 weeks, 6 and 12 months were 22.7 (standard deviation [SD], 25.9), 15.9 (SD, 21.5), and 16.1 (SD, 24.6), respectively. At 12 months, 16.5% reported more severe pain from the harvest site than the primary surgical site, 29.1% reported numbness, and 11.3% found the degree of numbness bothersome, whereas 3.9% were bothered by scar appearance. With respect to activity limitations resulting from harvest site pain at 1 year, 15.1% reported some difficulty walking, 5.2% with employment, 12.9% with recreation, 14.1% with household chores, 7.6% with sexual activity, and 5.9% irritation from clothing. CONCLUSIONS There is a significant rate of persistent pain and morbidity from iliac crest bone graft harvest when associated with elective spine surgery. Mean pain scores progressively decline over the first postoperative year. Nevertheless, harvest site pain remains functionally limiting in a significant percentage of patients 1 year after surgery. Rates of functional limitation are higher than previously reported and may be because of increased sensitivity of the prospective study design and targeted investigation of these specific symptoms. Validity of these findings is necessarily limited by patient ability to discriminate harvest site pain from alternative sources of back and buttock pain.

Risk factors for false positive transcranial motor evoked potential monitoring alerts during surgical treatment of cervical myelopathy.

Study Design. Retrospective consecutive series review. Objective. To examine performance of transcranial motor-evoked potential (TcMEP) monitoring in patients undergoing surgery for cervical myelopathy and potential risk factors for false positive alerts. Summary of Background Data. Although use of TcMEP monitoring has been increasing and has been specifically recommended in patients with cervical myelopathy, rates and risk factors for false positive alerts have not been established. Methods. Intraoperative neuromonitoring data for 52 consecutive patients undergoing surgery for cervical myelopathy were reviewed. All major TcMEP alerts were identified. Comprehensive demographic and clinical data, preoperative imaging studies, operative, and anesthesia records were reviewed. Results. Six of 52 patients (12%) experienced a major TcMEP alert consisting of sustained >80% loss of amplitude. There were no somatosensory-evoked potential (SSEP)-related alerts. In 2 cases, an intraoperative wake-up test was negative and in 3 cases, surgery was completed without a wake-up test and without recovery of TcMEP signals. No new postoperative neurologic deficits were observed in these patients. One patient with new postoperative weakness was correctly predicted by loss of TcMEP signals. No new deficit was observed in the remaining 46 patients. Statistical analysis revealed significantly higher body mass index (28.8 vs. 35.0; P = 0.032) and length of surgery (191 vs. 283 minutes; P = 0.019) in patients with false positive alerts. Conclusion. In this series of cervical myelopathy patients, sensitivity and specificity of TcMEP for detection of clinically significant intraoperative cord injury were 100% and 90%, respectively. Sensitivity and specificity of SSEP were 0% and 100%, respectively. The positive predictive value of a TcMEP alert was 17%. Possible risk factors for false positive TcMEP alerts include obesity and increased length of surgery. This study supports superior sensitivity of TcMEP compared with SSEP monitoring but identifies a relatively high false positive rate even in a selected high-risk cervical myelopathy population when this modality is applied in practice.

Metastatic disease of the cervical spine. A review.

The treatment of cervical metastatic disease requires a multidisciplinary team approach to evaluation and management and demands consideration of multiple factors before a regimen is accepted. The patients overall functioning and medical status, life expectancy, history of treatment, tumor type, and location within the cervical spine and individual vertebrae all must be evaluated carefully. The majority of lesions will be amenable to nonoperative aggressive modalities aimed at shrinking tumor size and halting growth. Surgical intervention is limited to specific indications, including spinal instability, progressive neurologic deterioration from bony collapse and compression, intractable pain, and failure of conservative means of treatment.

Computed tomography evaluation of superior-segment facet-joint violation after pedicle instrumentation of the lumbar spine with a midline surgical approach.

Study Design. Retrospective study. Objectives. To determine the frequency of pedicle screw violation of superior nonfused facet joints adjacent to the most cephalad pedicle screws after a midline approach for lumbar fusion. Summary of Background Data. Facet-joint violations have been evaluated in patients undergoing lumbar pedicle screw instrumentation and fusion with a Wiltse muscle-splitting approach, but not via the more common midline approach. Methods. Between 1995 and 2003, 204 patients underwent this procedure. Computed tomography scans (within 1 year postsurgery) were evaluated independently for superior facet-joint violation. &khgr;2 tests were used to examine bivariate associations of superior level facet-joint violation, patient age, construct level, diagnosis, and revision status for significance (P ≤ 0.05). Results. Superior-level facet-joint violation occurred in 24% of patients and 15% of screws, twice as often on the left side (P = 0.0396) than on the right, more frequently in single than in multiple-level procedures (P < 0.0001), and most frequently with the most cephalad screws at L5 (48%). We found no significant associations between violation rates and other designated parameters. Conclusion. The left side, single-level fusion, and most cephalad pedicle screws at L5 are targets for interventions to reduce pedicle violations in this procedure.

Polymorphic variation of the guanosine triphosphate cyclohydrolase 1 gene predicts outcome in patients undergoing surgical treatment for lumbar degenerative disc disease.

Study Design. Prospective observational study. Objective. To determine whether polymorphic variations of the guanosine triphosphate (GTP) cyclohydrolase 1 gene (GCH1) are associated with different outcomes in patients undergoing surgical treatment for lumbar degenerative disc disease (DDD). Summary of Background Data. GCH1, the gene encoding the rate-limiting enzyme in tetrahydrobiopterin synthesis, has been strongly implicated as a determinant of pain experience in previous animal and human studies. Methods. A total of 69 patients undergoing surgical treatment for lumbar DDD were prospectively enrolled. Genomic DNA was extracted from a venous blood sample, and DNA sequence analysis was performed of GCH1. Surgery included 65 instrumented fusions and 4 disc arthroplasty procedures. Patients were observed prospectively for 1 year following surgery. Allelic and genotype frequencies were calculated for each of 14 single nucleotide polymorphisms (SNPs). One-year postoperative Oswestry Disability Index (ODI) scores were compared to preoperative scores and the absolute change in ODI score was used to perform genetic association analyses on the basis of both individual SNP markers as well as commonly observed haplotypes for the entire gene sequence. Results. Single marker analysis revealed 1 SNP (rs998259; minor allele T) that was significantly associated with improvement in both absolute ODI score (P = 0.030) and Numerical Rating Scale back pain scores (P = 0.033) following surgery. Haplotype analysis identified a common GCH1 haplotype (“CACTTGTTTGAC”) with a sample frequency of 12.3%, which was highly associated with improvement in absolute ODI score (P = 0.04). This haplotype frequency reflects the existence of both heterozygous and homozygous individuals in the study population. The presence of 1 unit of this haplotype was associated with an improvement in postoperative ODI score of 15.34 relative to the absence of this haplotype (P = 0.04). Conclusion. Preliminary results from this pilot genetic study of patients undergoing surgery for DDD suggests that the T allele at rs998259 of GCH1 may be associated with improved outcomes 1 year following surgery.

Efficacy of silicate-substituted calcium phosphate ceramic in posterolateral instrumented lumbar fusion.

Study Design/Setting. Retrospective review of a consecutive, nonrandomized series operated on by 2 surgeons. Objective. To evaluate the clinical and radiographic effectiveness of a silicated hydroxyapatite ceramic as a bone graft substitute in a series of patients undergoing posterolateral instrumented lumbar fusion. Summary of Background Data. Newer-generation synthetic ceramics have been refined to maximize their host-graft interaction and stimulation of new tissue formation, including silicate-substitution. Methods. An independent radiologist interpreted the computed tomography images at 6, 12, and 24 months after surgery. Forty-two patients with 1- or 2-level lumbar degenerative disorders underwent posterior laminectomy (when indicated) and posterolateral fusion with instrumentation. Surgical levels included 15 patients who underwent 2-level and 27 single-level fusion procedures (57 levels operated on in total). Results. The average back pain scores improved from 5.6 ± 2.5 preoperative to 2.1 ± 2.5 at follow-up (P < 0.05). Similar results were seen with leg pain improvement from 5.8 ± 2.5 to 1.4 ± 1.9 (P < 0.05). At 6 months, 35% of levels revealed fusion, which increased to 76.2% and 76.5% at 12 and 24 months, respectively. No evidence of ectopic bone formation or osteolysis was noted. Conclusion. In this study, a silicated calcium phosphate-based ceramic has been shown to be effective as a graft substitute and eliminate the need for autogenous iliac crest bone graft. The results confirm radiographic healing in posterolateral instrumented lumbar fusion at 24-months follow-up. The clinical outcomes also substantiate significant pain improvement consistent with published data in the literature compared with other bone graft alternatives.

Prospective comparison of the effect of direct current electrical stimulation and pulsed electromagnetic fields on instrumented posterolateral lumbar arthrodesis.

The purpose of this prospective study was to compare the effect of adjunctive direct current (DC) electrical stimulation and pulsed electromagnetic field therapy (PEMF) on augmentation of instrumented lumbar fusion. Sixty-one patients undergoing lumbar spine fusion were enrolled in the study and randomized to one of three treatment protocols: 1) adjunctive PEMF group (n = 22) fitted with Spinal-Stim model 8212(AME) within 30 days of surgery; 2) DC group (n = 17) had a SpF-2T stimulator(EBI) implanted at the time of surgery; or 3) control group (n = 22). The fusion mass bone mineral density (BMD) assessment was performed on 3-month and 1-year radiographs for each patient. Lateral flexion-extension and anteroposterior radiographs were evaluated at 1 year to determine the presence of fusion. Clinical outcome patient analyses were performed at 1 year. At 1-year follow-up, radiographic fusion and fusion mass bone density were not significantly different among the groups. In the nonstimulated group, there were 43% excellent, 43% good, and 14% fair results. In the PEMF group, there were 35% excellent, 50% good, 10% fair, and 5% poor results. In the DC group, there were 32% excellent, 37% good, and 31% fair results. The results of the current study suggest that electrical stimulation does not significantly enhance fusion rate in instrumented lumbar arthrodesis, although we observed a statistically insignificant trend toward increased fusion mass BMD in the electrically stimulated groups. The significance of increased BMD remains unknown.

late Vascular Complication With Anterior Cervical Discectomy and Fusion

Study Design. The authors report a patient with delayed inferior thyroid artery pseudoaneurysm after uneventful anterior cervical discectomy and fusion. Methods. The Smith‐Robinson approach to the anterior cervical spine is a commonly used and relatively safe surgical approach for cervical disc disease. Results. This case is unusual in two respects: 1) the vascular complication occurred 9 days postoperatively; and 2) the inferior thyroid artery was embolized without the need for immediate exploration and surgical ligation. Conclusion. The patient was successfully managed with therapeutic embolization. [Key words: anterior discectomy, embolization, Smith‐Robinson approach, vascular complications] Spine 1994;19:1291–1293