Advertisement

Child's Nervous System

, Volume 34, Issue 9, pp 1705–1716 | Cite as

Outcomes from 18 years of cervical spine surgery in MPS IVA: a single centre’s experience

  • A. Broomfield
  • K. Zuberi
  • J. Mercer
  • G. Moss
  • N. Finnegan
  • P. Hensman
  • R. Walker
  • S. Bukhari
  • N. B. Wright
  • F. Stewart
  • S. A. Jones
  • R. Ramirez
Original Paper

Abstract

Purpose

This study examines the long-term outcomes of paediatric Morquio (MPS IVA) patients undergoing cervical spine surgery and evaluates the factors that impacting this.

Methods

A retrospective review was performed on all MPS IVA patients undergoing cervical spine surgery, since the introduction of standardised neuroradiological screening. The impact of preoperative neurological status, growth, genotype and radiological status on outcome is assessed, whilst long-term surgical, radiological and neurological outcomes are documented.

Results

Twenty-six of the eighty-two MPS IVA patients (31%) reviewed underwent cervical spine surgery at a median age of 6.1 years (range, 1.45 to 15.24). Preoperatively, cord signal change was seen in 11 patients with 5 being myelopathic; however, 6 clinically manifesting patients had no overt cord signal change. Postoperatively, none of the 14 preoperatively clinically asymptomatic patients followed long term progressed neurologically during a median follow-up of 77.5 months (range = 18–161). Of the ten preoperatively clinically symptomatic patients who were followed up for the same duration, seven continued to deteriorate, two initially improved and one remained stable. Radiological follow-up performed for a median duration of 7 years (range = 0.5–16) has shown a degree of stenosis at the level immediately caudal to the termination of the graft in 76% of patients, though only one has become clinically symptomatic and required revision.

Conclusions

Once clinically elicitable neurological signs become evident in patients with MPS IVA, they tend to progress despite surgical intervention. Referring clinicians should also not be falsely reassured by the lack of T2 spinal cord signal change but should consider surgical intervention in the face of new clinical symptomology or radiological signs of progressive canal stenosis or instability.

Keywords

Morquio syndrome Dysostosis multiplex Cervical spine Magnetic resonance imaging Myelopathy 

Notes

Acknowledgments

The authors would like to acknowledge both Professor JE Wraith and Mr. R Cowie, who between them cared for and operated on the majority of these patients and whose dedication underlies the majority of this manuscript. We would also like to acknowledge the contribution of Mr. J Thorne whose work and advice was integral to many patients on this paper.

Compliance with ethical standards

Conflicts of interest

Dr. Broomfield, Mr. Zuberi, Miss Mercer, Miss Moss and Dr. Jones have received financial support for attending symposia from Biomarin. The other authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. As this is a retrospective study, formal consent is not required.

References

  1. 1.
    Masuno M, Tomatsu S, Nakashima Y, Hori T, Fukuda S, Masue M, Sukegawa K, Orii T (1993) Mucopolysaccharidosis IV a: assignment of the human N-acetylgalactosamine-6-sulfate sulfatase (GALNS) gene to chromosome 16q24. Genomics 16:777–778CrossRefPubMedGoogle Scholar
  2. 2.
    Glossl J, Kresse H (1982) Impaired degradation of keratan sulphate by Morquio a fibroblasts. Biochem J 203:335–338CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Matalon R, Dorfman A (1974) Sanfilippo a syndrome: sulfamidase deficiency in cultured skin fibroblasts and liver. J Clin Invest 54:907–912CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Khan S, Almeciga-Diaz CJ, Sawamoto K, Mackenzie WG, Theroux MC, Pizarro C et al (2017) Mucopolysaccharidosis IVA and glycosaminoglycans. Mol Genet Metab 120:78–95CrossRefPubMedGoogle Scholar
  5. 5.
    Pomin VH (2015) Keratan sulfate: an up-to-date review. Int J Biol Macromol 72:282–289CrossRefPubMedGoogle Scholar
  6. 6.
    Montano AM, Tomatsu S, Gottesman GS, Smith M, Orii T (2007) International Morquio a registry: clinical manifestation and natural course of Morquio a disease. J Inherit Metab Dis 30:165–174CrossRefPubMedGoogle Scholar
  7. 7.
    Lavery C, Hendriksz C (2015) Mortality in patients with morquio syndrome A. JIMD Rep 15:59–66PubMedGoogle Scholar
  8. 8.
    Montano AM, Tomatsu S, Brusius A, Smith M, Orii T (2008) Growth charts for patients affected with Morquio a disease. Am J Med Genet A 146A:1286–1295CrossRefPubMedGoogle Scholar
  9. 9.
    Northover H, Cowie RA, Wraith JE (1996) Mucopolysaccharidosis type IVA (Morquio syndrome): a clinical review. J Inherit Metab Dis 19:357–365CrossRefPubMedGoogle Scholar
  10. 10.
    Stevens JM, Kendall BE, Crockard HA, Ransford A (1991) The odontoid process in Morquio-Brailsford’s disease. The effects of occipitocervical fusion. J Bone Joint Surg Br 73:851–858CrossRefPubMedGoogle Scholar
  11. 11.
    Solanki GA, Martin KW, Theroux MC, Lampe C, White KK, Shediac R, Lampe CG, Beck M, Mackenzie WG, Hendriksz CJ, Harmatz PR (2013) Spinal involvement in mucopolysaccharidosis IVA (Morquio-Brailsford or Morquio a syndrome): presentation, diagnosis and management. J Inherit Metab Dis 36:339–355CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Solanki GA, Lo WB, Hendriksz CJ (2013) MRI morphometric characterisation of the paediatric cervical spine and spinal cord in children with MPS IVA (Morquio-Brailsford syndrome). J Inherit Metab Dis 36:329–337CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Lipson SJ (1977) Dysplasia of the odontoid process in Morquio’s syndrome causing quadriparesis. J Bone Joint Surg Am 59:340–344CrossRefPubMedGoogle Scholar
  14. 14.
    White KK, Steinman S, Mubarak SJ (2009) Cervical stenosis and spastic quadriparesis in Morquio disease (MPS IV). A case report with twenty-six-year follow-up. J Bone Joint Surg Am 91:438–442CrossRefPubMedGoogle Scholar
  15. 15.
    Baratela WA, Bober MB, Thacker MM, Belthur MV, Oto M, Rogers KJ et al (2014) Cervicothoracic myelopathy in children with Morquio syndrome a: a report of 4 cases. J Pediatr Orthop 34:223–228CrossRefPubMedGoogle Scholar
  16. 16.
    Ransford AO, Crockard HA, Stevens JM, Modaghegh S (1996) Occipito-atlanto-axial fusion in Morquio-Brailsford syndrome. A ten-year experience. J Bone Joint Surg Br 78:307–313CrossRefPubMedGoogle Scholar
  17. 17.
    Charrow J, Alden TD, Breathnach CA, Frawley GP, Hendriksz CJ, Link B et al (2015) Diagnostic evaluation, monitoring, and perioperative management of spinal cord compression in patients with Morquio syndrome. Mol Genet Metab 114:11–18CrossRefPubMedGoogle Scholar
  18. 18.
    Dede O, Thacker MM, Rogers KJ, Oto M, Belthur MV, Baratela W, Mackenzie WG (2013) Upper cervical fusion in children with Morquio syndrome: intermediate to long-term results. J Bone Joint Surg Am 95:1228–1234CrossRefPubMedGoogle Scholar
  19. 19.
    Walker RW, Darowski M, Morris P, Anaesthesia WJE (1994) Mucopolysaccharidoses. A review of airway problems in children. Anaesthesia 49:1078–1084CrossRefPubMedGoogle Scholar
  20. 20.
    Berger KI, Fagondes SC, Giugliani R, Hardy KA, Lee KS, McArdle C, Scarpa M, Tobin MJ, Ward SA, Rapoport DM (2013) Respiratory and sleep disorders in mucopolysaccharidosis. J Inherit Metab Dis 36:201–210CrossRefPubMedGoogle Scholar
  21. 21.
    Pelley CJ, Kwo J, Hess DR (2007) Tracheomalacia in an adult with respiratory failure and Morquio syndrome. Respir Care 52:278–282PubMedGoogle Scholar
  22. 22.
    Hughes DG, Chadderton RD, Cowie RA, Wraith JE, Jenkins JP (1997) MRI of the brain and craniocervical junction in Morquio’s disease. Neuroradiology 39(5):381–385CrossRefPubMedGoogle Scholar
  23. 23.
    Tomatsu S, Montano AM, Nishioka T, Gutierrez MA, Pena OM, Tranda Firescu GG et al (2005) Mutation and polymorphism spectrum of the GALNS gene in mucopolysaccharidosis IVA (Morquio a). Hum Mutat 26:500–512CrossRefPubMedGoogle Scholar
  24. 24.
    Tomatsu S, Fukuda S, Cooper A, Wraith JE, Rezvi GM, Yamagishi A, Yamada N, Kato Z, Isogai K, Sukegawa K (1995) Mucopolysaccharidosis IVA: identification of a common missense mutation I113F in the N-Acetylgalactosamine-6-sulfate sulfatase gene. Am J Hum Genet 57:556–563PubMedPubMedCentralGoogle Scholar
  25. 25.
    Mackenzie WG, Dhawale AA, Demczko MM, Ditro C, Rogers KJ, Bober MB, Campbell JW, Grissom LE (2013) Flexion-extension cervical spine MRI in children with skeletal dysplasia: is it safe and effective? J Pediatr Orthop 33:91–98CrossRefPubMedGoogle Scholar
  26. 26.
    Boor R, Miebach E, Bruhl K, Beck M (2000) Abnormal somatosensory evoked potentials indicate compressive cervical myelopathy in mucopolysaccharidoses. Neuropediatrics 31:122–127CrossRefPubMedGoogle Scholar
  27. 27.
    Mollmann C, Lampe CG, Muller-Forell W, Scarpa M, Harmatz P, Schwarz M et al (2013) Development of a scoring system to evaluate the severity of craniocervical spinal cord compression in patients with Mucopolysaccharidosis IVA (Morquio a syndrome). JIMD Rep. 11:65–72CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Tobert DG, Glotzbecker MP, Hresko MT, Karlin LI, Proctor MR, Emans JB, Miller PE, Hedequist DJ (2017) Efficacy of intraoperative neurophysiologic monitoring for pediatric cervical spine surgery. Spine (Phila Pa 1976) 42:974–978CrossRefGoogle Scholar
  29. 29.
    Elsamadicy AA, Adogwa O, Lydon E, Reddy G, Kaakati R, Sergesketter A et al (2017) Impact of intraoperative monitoring during elective complex spinal fusions (>/= 4 levels) on 30-day complication and readmission rates: a single institutional study of 643 adult spinal deformity patients. World NeurosurgGoogle Scholar
  30. 30.
    Elsamadicy AA, Adogwa O, Behrens S, Sergesketter A, Chen A, Mehta AI, Vasquez RA, Cheng J, Bagley CA, Karikari IO Impact of surgical approach on complication rates after elective spinal fusion (>/=3 levels) for adult spine deformity. J Spine Surg 2017;3:31–37Google Scholar
  31. 31.
    Walker R, Belani KG, Braunlin EA, Bruce IA, Hack H, Harmatz PR, Jones S, Rowe R, Solanki GA, Valdemarsson B (2013) Anaesthesia and airway management in mucopolysaccharidosis. J Inherit Metab Dis 36:211–219CrossRefPubMedGoogle Scholar
  32. 32.
    Morimoto N, Kitamura M, Kosuga M, Okuyama T (2014) CT and endoscopic evaluation of larynx and trachea in mucopolysaccharidoses. Mol Genet Metab 112:154–159CrossRefPubMedGoogle Scholar
  33. 33.
    Yasuda E, Fushimi K, Suzuki Y, Shimizu K, Takami T, Zustin J, Patel P, Ruhnke K, Shimada T, Boyce B, Kokas T, Barone C, Theroux M, Mackenzie W, Nagel B, Ryerse JS, Orii KE, Iida H, Orii T, Tomatsu S (2013) Pathogenesis of Morquio a syndrome: an autopsied case reveals systemic storage disorder. Mol Genet Metab 109:301–311CrossRefPubMedGoogle Scholar
  34. 34.
    Bank RA, Groener JE, van Gemund JJ, Maaswinkel PD, Hoeben KA, Schut HA et al (2009) Deficiency in N-acetylgalactosamine-6-sulfate sulfatase results in collagen perturbations in cartilage of Morquio syndrome a patients. Mol Genet Metab 97:196–201CrossRefPubMedGoogle Scholar
  35. 35.
    Reintjes SL, Amankwah EK, Rodriguez LF, Carey CC, Tuite GF (2015) Allograft versus autograft for pediatric posterior cervical and occipito-cervical fusion: a systematic review of factors affecting fusion rates. J Neurosurg Pediatr:1–16Google Scholar
  36. 36.
    Kecskemethy HH, Kubaski F, Harcke HT, Tomatsu S (2016) Bone mineral density in MPS IV a (Morquio syndrome type a). Mol Genet Metab 117:144–149CrossRefPubMedGoogle Scholar
  37. 37.
    Harms J, Melcher RP (2001) Posterior C1-C2 fusion with polyaxial screw and rod fixation. Spine (Phila Pa 1976) 26:2467–2471CrossRefGoogle Scholar
  38. 38.
    Vanek P, Homolkova H, Benes V, Zeman J (2015) Occipitocervical stabilization using bilateral laminar C2 screws in children with mucopolysaccharidosis IVA. Eur Spine J 24:2756–2762CrossRefPubMedGoogle Scholar
  39. 39.
    LECTd S, AGCd B, Cavalcanti LR, CJd C, Tavares RH, RTd S (2016) Results of surgical treatment in the craniocervical junction in mucopolysaccharidosis. Coluna/Columna 15:57–60CrossRefGoogle Scholar
  40. 40.
    Bransford RJ, Lee MJ, Reis A (2011) Posterior fixation of the upper cervical spine: contemporary techniques. J Am Acad Orthop Surg 19:63–71CrossRefPubMedGoogle Scholar
  41. 41.
    Ain MC, Chaichana KL, Schkrohowsky JG (2006) Retrospective study of cervical arthrodesis in patients with various types of skeletal dysplasia. Spine (Phila Pa 1976) 31:E169–E174CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Willink Biochemical Genetics Unit, Manchester Centre for Genomic MedicineSt Mary’s Hospital, Central Manchester Foundation TrustManchesterUK
  2. 2.Faculty of Biology, Medicine and HealthThe University of ManchesterManchesterUK
  3. 3.Department of PhysiotherapyRoyal Manchester Children’s Hospital, Central Manchester Foundation TrustManchesterUK
  4. 4.Department of Paediatric AnaestheticsRoyal Manchester Children’s Hospital, Central Manchester Foundation TrustManchesterUK
  5. 5.Department of Paediatric NeurosurgeryRoyal Manchester Children’s Hospital, Central Manchester Foundation TrustManchesterUK
  6. 6.Department of Paediatric RadiologyRoyal Manchester Children’s Hospital, Central Manchester Foundation TrustManchesterUK
  7. 7.N.I Regional Genetics Service, Level ABelfast City HospitalBelfastUK

Personalised recommendations