Complications in Adult Patients with Down Syndrome Undergoing Cervical Spine Surgery Using Current Instrumentation Techniques and rhBMP-2: A Long-Term Follow-Up

Abstract

Introduction Cervical spine pathologies are common in Down syndrome (DS) patients. Cervical pathologies may cause cord compression and neurologic deterioration if left untreated. Complication rates of 73–100% have been reported in DS patients after cervical spine surgery in historical studies. This study reports updated perioperative complications rates and long-term outcome in patients with DS undergoing cervical spine surgery.

Methods Retrospective review of patients with DS who have undergone cervical spine surgery from 1998 to 2011 (≥ 24 months of follow-up) was undertaken. Series of 17 adults with preoperative diagnoses that included atlantoaxial instability, stenosis, spondylosis, or cervical spondylolisthesis were evaluated. Nine patients received recombinant human bone morphogenetic protein-2 (rhBMP-2). Neurologic and ambulatory status was evaluated at regular intervals included pre- and postoperative imaging, range of motion evaluation, strength/neurologic testing, ambulation observation, and patient and caretaker pain reporting.

Results A total of 20 surgical procedures were performed in 17 patients. Average follow-up was 78.7 months (range: 25–156 months). Overall, 37 complications were observed including pneumonia, respiratory distress, reintubation, dysphagia, deep venous thrombosis, sepsis, wound infection, dehiscence, neurologic complications, loss of reduction (LOR), pseudarthrosis, and hardware failure. Postoperative pneumonia was most common (23.5%). Three patients developed pseudarthrosis (all in the rhBMP-2 group); three demonstrated LOR. Neurologic complications (N = 3) included spasticity, loss of ambulation, and postoperative weakness with myelomalacia. Two were transient. Respiratory complications in the rhBMP-2 group were the most common (N = 3). The anterior approach resulted in a higher likelihood of complications than the posterior (p = 0.032).

Conclusions Current techniques may improve pseudarthrosis (p = 0.009), LOR (p = 0.043), and first attempt (p = 0.038) and overall fusion rates (p = 0.018) compared with historical studies. Complications continue to challenge most patients (82.4%). A total of 16 of 17 patients (94.1%) demonstrated stabilization or improvement in neurologic status. Apparent successful outcome in the majority appears to warrant the high complication risk associated with cervical spine surgery in DS patients. The anterior approach resulted in a higher risk of complications than posterior (p = 0.032). We report a higher than expected incidence of pseudarthrosis in DS patients receiving rhBMP-2, putting its benefit in DS patients into question.

Keywords

spine surgery complications - Down syndrome - cervical spine pathologies in Down syndrome - cervical spine in Down syndrome

• References

• 1 Mik G, Gholve PA, Scher DM, Widmann RF, Green DW. Down syndrome: orthopedic issues. Curr Opin Pediatr 2008; 20 (1) 30-36
• 2 Hankinson TC, Anderson RC. Craniovertebral junction abnormalities in Down syndrome. Neurosurgery 2010; 66 (3, Suppl): 32-38
• 3 Tassone JC, Duey-Holtz A. Spine concerns in the Special Olympian with Down syndrome. Sports Med Arthrosc Rev 2008; 16 (1) 55-60
• 4 Menezes AH, Ryken TC. Craniovertebral abnormalities in Down's syndrome. Pediatr Neurosurg 1992; 18 (1) 24-33
• 5 Ali FE, Al-Bustan MA, Al-Busairi WA, Al-Mulla FA, Esbaita EY. Cervical spine abnormalities associated with Down syndrome. Int Orthop 2006; 30 (4) 284-289
• 6 Nordt JC, Stauffer ES. Sequelae of atlantoaxial stabilization in two patients with Down's syndrome. Spine 1981; 6 (5) 437-440
• 7 Segal LS, Drummond DS, Zanotti RM, Ecker ML, Mubarak SJ. Complications of posterior arthrodesis of the cervical spine in patients who have Down syndrome. J Bone Joint Surg Am 1991; 73 (10) 1547-1554
• 8 Doyle JS, Lauerman WC, Wood KB, Krause DR. Complications and long-term outcome of upper cervical spine arthrodesis in patients with Down syndrome. Spine 1996; 21 (10) 1223-1231
• 9 Smith MD, Phillips WA, Hensinger RN. Fusion of the upper cervical spine in children and adolescents. An analysis of 17 patients. Spine 1991; 16 (7) 695-701
• 10 Curtis BH, Blank S, Fisher RL. Atlantoxial dislocation in Down's syndrome. Report of two patients requiring surgical correction. JAMA 1968; 205 (6) 464-465
• 11 Dzenitis AJ. Spontaneous atlanto-axial dislocation in a mongoloid child with spinal cord compression. Case report. J Neurosurg 1966; 25 (4) 458-460
• 12 Pueschel SM, Herndon JH, Gelch MM, Senft KE, Scola FH, Goldberg MJ. Symptomatic atlantoaxial subluxation in persons with Down syndrome. J Pediatr Orthop 1984; 4 (6) 682-688
• 13 Davidson RG. Atlantoaxial instability in individuals with Down syndrome: a fresh look at the evidence. Pediatrics 1988; 81 (6) 857-865
• 14 Cremers MJ, Ramos L, Bol E, van Gijn J. Radiological assessment of the atlantoaxial distance in Down's syndrome. Arch Dis Child 1993; 69 (3) 347-350
• 15 Roy M, Baxter M, Roy A. Atlantoaxial instability in Down syndrome—guidelines for screening and detection. J R Soc Med 1990; 83 (7) 433-435
• 16 Lovecchio F, Hsu WK, Smith TR, Cybulski G, Kim B, Kim JY. Predictors of thirty-day readmission after anterior cervical fusion. Spine 2014; 39 (2) 127-133
• 17 Nandyala SV, Marquez-Lara A, Fineberg SJ, Singh K. Comparison between cervical total disc replacement and anterior cervical discectomy and fusion of 1 to 2 levels from 2002 to 2009. Spine 2014; 39 (1) 53-57
• 18 Burkhardt JK, Mannion AF, Marbacher S , et al. A comparative effectiveness study of patient-rated and radiographic outcome after 2 types of decompression with fusion for spondylotic myelopathy: anterior cervical discectomy versus corpectomy. Neurosurg Focus 2013; 35 (1) E4
• 19 Tannoury CA, An HS. Complications with the use of bone morphogenetic protein 2 (BMP-2) in spine surgery. Spine J 2014; 14 (3) 552-559
• 20 Epstein NE. Complications due to the use of BMP/INFUSE in spine surgery: The evidence continues to mount. Surg Neurol Int 2013; 4 (Suppl. 05) S343-S352
• 21 Carragee EJ, Hurwitz EL, Weiner BK. A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned. Spine J 2011; 11 (6) 471-491
• 22 Alpert S. AMPLIFY^TM rhBMP-2 Matrix. Orthopaedic and Rehabilitation Devices Advisory Panel Presentation; July 27, 2010;Washington, DC. Available at: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/OrthopaedicandRehabilitationDevicesPanel/UCM220741.pdf
• 23 Koehler SM, Latridis JC, Hecht A , et al. Does BMP-2 really cause cancer? A systematic review of the literature—NASS meeting 2012. Spine J 2012; 12 (9) S143-S144
• 24 Skovrlj B, Koehler SM, Anderson PA , et al. Association between BMP-2 and carcinogenicity. Spine 2015; 40 (23) 1862-1871
• 25 Chrastil J, Low JB, Whang PG, Patel AA. Complications associated with the use of the recombinant human bone morphogenetic proteins for posterior interbody fusions of the lumbar spine. Spine 2013; 38 (16) E1020-E1027
• 26 Singh K, Ahmadinia K, Park DK , et al. Complications of spinal fusion with utilization of bone morphogenetic protein: a systematic review of the literature. Spine 2014; 39 (1) 91-101
• 27 Faundez A, Tournier C, Garcia M, Aunoble S, Le Huec JC. Bone morphogenetic protein use in spine surgery-complications and outcomes: a systematic review. Int Orthop 2016; March 10 ( Epub ahead of print).
• 28 Wilcock DM, Griffin WS. Down's syndrome, neuroinflammation, and Alzheimer neuropathogenesis. J Neuroinflammation 2013; 10: 84
• 29 Zlokovic BV. Cerebrovascular effects of apolipoprotein E: implications for Alzheimer disease. JAMA Neurol 2013; 70 (4) 440-444