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A retrospective review of the clinical and radiographic outcomes from a multicenter study of surgical treatment for high-grade spondylolisthesis (HGS) in adults. The objective was to assess the safety of surgical reduction, its ability to correct regional deformity, and its clinical effectiveness.Retrospective, multicenter review of adults (age above 18 y) with lumbosacral HGS (Meyerding grade 3–5) treated surgically with open decompression, attempted reduction, posterior instrumentation, and interbody fusion. Preoperative and postoperative assessment of the Meyerding grade, slip angle, and sacral inclination were performed based on standing radiographs. Preoperative visual analog scale scores were compared with those at the mean follow-up period. Prolo and Oswestry Disability Index scores at most recent follow-up were assessed.A total of 25 patients, aged 19–72 years, met inclusion criteria. Seventeen interbody cages were placed, including 15 transforaminal lumbar interbody fusions, 1 posterior lumbar interbody fusion, and 1 anterior lumbar interbody fusion. Five patients required sacral dome osteotomies. The average follow-up was 21.3 months.At most recent follow-up there was a statistically significant improvement in both the Meyerding grade and the slip angle (P<0.05). There was 1 intraoperative complication resulting in a neurological deficit (4%) and 1 intraoperative vertebral body fracture (4%). No additional surgery was required for any of these patients. There were no cases of nonunion or device failure except for 1 patient who suffered an unrelated traumatic injury 1 year after surgery. The mean Oswestry Disability Index and Prolo scores at mean follow-up of 21.3 months were 20% (minimum disability) and 8.2 (grade 1), respectively.The present study suggests that reduction, when accomplished in conjunction with wide neural element decompression and instrumented arthrodesis, is safe, effective, and durable with low rates of neurological injury, favorable clinical results, and high-fusion rates.