spinal involvement in morquio a. atlantoaxial system: anatomy and pathology articulation of c1...
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Spinal involvement in Morquio A
Atlantoaxial system: anatomy and pathology
Articulation of C1 (atlas) with C2 (axis) is complex, comprising
several joints
– Median atlantoaxial joint
– Two lateral atlantoaxial joints
These joints are held in place and supported by several ligaments
– Major stabilizing ligaments are the transverse and alar
ligaments
Incompetent ligaments and/or dens hypoplasia may cause
excessive independent movement between the C1 anterior arch
and the dens to result in atlantoaxial subluxation and instability
– During flexion, spinal cord compression at the C1-C2 level
results from indentation by the C1 posterior arch and posterior
tilting of the dens
Upward translation of the dens may also result from transverse
ligament failure
– Vertical subluxation can lead to compression of the medulla,
paralysis and death
Solanki et al, J Inherit Metab Dis, 2013
Competent transverse and alar ligaments maintain the integrity of the C1-C2 articulation by limiting posterior translation of the dens (odontoid process)
Top image courtesy of Michael Beck, MD, and Christina Lampe, MDBottom image courtesy of Christina Lampe, MD
Spinal involvement is a major cause of morbidity and mortality in Morquio A Syndrome
Spectrum of spinal involvement:– Bony anomalies– Cervical spine subluxation and
instability– Spinal canal stenosis– Spinal cord compression
Spinal problems predispose patients to myelopathy, paralysis, and premature death
Solanki et al, J Inherit Metab Dis, 2013; Montano et al, J Inherit Metab Dis, 2007; Tomatsu et al, Curr Pharm Biotechnol, 2011
Harmatz et al, Mol Genet Metab, 2013
MorCAP baseline data
Spinal involvement is common in Morquio A
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n = 325 Morquio A subjects (mean age = 14.5 years)Data based on medical history reviews
Dens hypoplasiaPlatyspondylyAnterior beakingPosterior scalloping Thoracolumbar kyphosis
Solanki et al, J Inherit Metab Dis, 2013
Bony anomalies: Dysostosis multiplex
Etiology:– dens hypoplasia– ligamentous laxityAtlantoaxial (C1-C2) subluxation:– ADI > 5 mm or PADI < 14 mmInstability is present when ADI difference between flexion/extension views > 2 mm
Solanki et al, J Inherit Metab Dis, 2013
Cervical spine subluxation and instability
Risk of cord compression and neurological compromise especially in presence of cervical spinal canal stenosis
Etiology
– Diffuse stenosis: Generalized thickening of the posterior longitudinal
ligament and the ligamentum flavum due to GAG accumulation
Most likely to result in compression at C4-C7 and T10-L1
– Focal stenosis: CCJ: thickening of the membrana tectoria and apical
and occipito-atlantal ligaments C1-C2: thickening of the peri-odontoid tissue and
transverse atlantoaxial ligament + C1 posterior arch C3-C7: bulging discs Thoracolumbar and upper thoracic spine: kyphosis
Solanki et al, J Inherit Metab Dis, 2013
Spinal canal stenosis
Etiology:
– Thickened ligaments
– Cervical instability
– Cartilaginous and ligamentous hypertrophy at the C1-C2 joint
– Spinal canal stenosis
– Disc protrusion
– Kyphosis
Spinal canal stenosis or a combination of stenosis and instability may be predictive of spinal cord compression
Spinal stenosis with concomitant loss of CSF flow on MRI signifies spinal cord compression
Untreated cord compression can lead to cord damage and myelopathy
Solanki et al, J Inherit Metab Dis, 2013
Spinal cord compression
Image courtesy of Kenneth Martin, MD
Diagnostic and monitoring tools:
Neurological examination
Imaging– Radiography– Computed tomography (CT)– Magnetic resonance imaging (MRI)
Other diagnostic examinations– Functional testing (e.g. 6 minute
walk test)– Sleep studies– Urodynamics
Solanki et al, J Inherit Metab Dis, 2013
Early recognition and diagnosis of spinal problems can minimize morbidity and mortality
Neurological examination can identify patients
at early stages of spinal cord compressionPresenting symptoms include loss of endurance, diminished walking distance, gait instability, leg weakness, paresthesia (legs and/or arms)
Hyperreflexia, raised muscle tone, pyramidal tract signs (ankle clonus, Babinski sign) and proprioceptive deficits may be observed upon examination
– Limitations: Morquio A patients may be difficult to assess
neurologically due to lower limb joint involvement
neurological signs and symptoms may underestimate the severity of spinal cord compression seen on MRI
determination of the responsible level is challenging in patients with multi-segmental myelopathy
Solanki et al, J Inherit Metab Dis, 2013
Images courtesy of Kenneth Martin, MD
Goals of imaging:– Detect treatable spinal cord compression– Stratify risk to spinal cord prior to
permanent loss of function– Assist in surgical planning– Assess efficacy of surgical and medical
treatment
Systematic and careful imaging involves:– Plain radiography, including instability
imaging– MRI of the spinal cord– CT may be required
Clinical and neurological findings should be correlated with imaging studies
Solanki et al, J Inherit Metab Dis, 2013
Imaging is critical for risk assessment and diagnosis of spinal cord compression
Strengths Limitations
Assess bone malformation
Assess spinal canal stenosis
Assess malalignment
Flexion-extension instability
Rapid
Inexpensive
Poor soft tissue discrimination
Limited by overlapping structures
Ionizing radiation
Limited to ossified structures
Radiography
Solanki et al, J Inherit Metab Dis, 2013
Strengths Limitations
Rapid (may obviate need for anesthesia)
Multiplanar imaging of bony structures
Alternative method for assessing flexion-extension instability in difficult cases (recommend low radiation dose protocol)
Can assess some soft tissue components of canal stenosis and cord compression with appropriate filtering
Preoperative planning
Suboptimal for visualizing soft tissues and the spinal cord
Ionizing radiation
More expensive and less accessible than plain film radiography
CT
Solanki et al, J Inherit Metab Dis, 2013
Strengths Limitations
Multiplanar imaging
Ideal for soft tissue imaging
Preferred method for assessing spinal cord compression and myelomalacia
Flexion-extension imaging directly visualizes spinal cord
Demonstrate venous collaterals
Non-ionizing radiation
Long imaging times
May require anesthesia
Metal and motion artifacts
Limited access
Expensive
MRI
Solanki et al, J Inherit Metab Dis, 2013
Myelomalacia is diagnosed by an increase in T2 signal coupled with volume loss in regions of cord compression
MRI sequences:– T1– T2– Cisternography– CSF Flow– Diffusion– Spectroscopy– MR venography
Solanki et al, J Inherit Metab Dis, 2013
MRI is the single most useful tool for assessing spinal cord compression
Natural history of cord compression
Solanki et al, Mol Genet Metab, 2012
Normal Cord Function- Canal stenosis
without contact or compression
Normal Cord Function- CSF effacement and
cord contact
Normal Cord Function- Cord compression with
normal T2, diffusivity and spectroscopy
Cord dysfunction, possibly reversible - Cord compression with normal T2,
but altered diffusivity and spectroscopy
Cord dysfunction, probably arrestable, may not be reversible
- Cord compression with abnormal T2, indicating myelomalacia or
edema
- Threshold for critical cord compression -
Assessment At diagnosis Frequency
Neurological exam Yes 6 months
Plain radiography cervical spine (AP, lateral neutral and flexion-extension)
Yes 2-3 years
Plain radiography spine (AP, lateral thoracolumbar)
Yes2-3 years if evidence
of kyphosis or scoliosis
MRI neutral position, whole spine Yes 1 year
Flexion-extension of cervical spine by MRI
Yes 1-3 years
CT neutral region of interest Preoperative planning
Solanki et al, J Inherit Metab Dis, 2013
Regular assessments are recommended for improved patient outcomes
White, Curr Orthop Prac, 2012
Ain et al, Spine, 2006
Indications include:– Neurological deficits + instability– Cord compression with signal change on MRI
Cervical spine:– Posterior fusion for C1-C2 subluxation and
instability, often with posterior occipito-cervical fixation
– If subluxation is irreducible and cord compression is present, decompression + fusion is indicated
– Prophylatic fusion recommended by some
Thoracolumbar kyphosis:– Decompression, segmental instrumentation
and fusion– Anterior discectomy and fusion strongly
recommended to augment posterior fusion in cases of rigid kyphosis
Solanki et al, J Inherit Metab Dis, 2013; White, Curr Orthop Prac, 2012; Ain et al, Spine (Phila PA 1976), 2006; Ransford et al, J Bone Joint Surg Br, 1996; Lipson, J Bone Joint Surg Am, 1977
Surgical interventions
Morquio patient 26 years post-surgery: complete resolution of quadriparesis achieved and neurological function maintained 26 years after C1-C2 decompression and stabilization White, J Bone Joint Surg Am, 2009
Short-term post-operative outcomes generally good
Possible post-surgical complications:
– Late instability below fusion site may necessitate multiple fusions
– Halo pin tract infection
→ Long-term monitoring is important
Long-term outcomes beyond 5 years are less known – few studies
Solanki et al, J Inherit Metab Dis, 2013; White, J Bone Joint Surg Am, 2009; Ain et al, Spine (Phila PA 1976), 2006; Dalvie et al, J Pediatr Orthop B, 2001; Holte et al, Neuro-Orthopedics,1994; Houten et al, Pediatr Neurosurg, 2011; Lipson, J Bone Joint Surg Am, 1977; Ransford et al, J Bone Joint Surg Br, 1996; Stevens et al, J Bone Joint Surg Br 1991; Svensson and Aaro, Act Orthop Scand, 1988.
Surgical outcomes
Morquio A patients are at high risk of anesthesia-related morbidity and mortality due to:– Cervical instability and myelopathy– Compromised respiratory function
Upper and lower airway obstruction Restrictive lung disease
– Cardiac abnormalities
Any elective surgery requires:– Thorough pre-operative ENT, pulmonary and cardiac evaluations– Pre-operative radiological evaluation of the cervical spine – Skilled personnel in airway management– Spectrum of airway management equipment
Morquio A patients should be managed by experienced anesthesiologists at centers familiar with MPS disorders
Theroux et al, Paediatr Anaesth, 2012; Solanki et al, J Inherit Metab Dis, 2013; Walker et al, J Inherit Metab Dis, 2013;
McLaughlin et al, BMC Anesthesiol, 2010; Morgan et al, Paediatr Anaesth, 2002; Shinhar et al, Arch Otolaryngol Head Neck Surg, 2004;
Belani et al, J Ped Surg, 1993; Walker et al, Anaesthesia, 1994
Airway and anesthetic management of Morquio A patients presenting for surgery is challenging