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
Competent transverse and alar
ligaments maintain the integrity of
the C1-C2 articulation by limiting
posterior translation of the dens
(odontoid process)
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
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
Top image courtesy of Michael Beck, MD, and Christina Lampe, MD
Bottom image courtesy of Christina Lampe, MD
Solanki et al, J Inherit Metab Dis, 2013; Montano et al, J Inherit Metab Dis, 2007; Tomatsu et al, Curr Pharm Biotechnol, 2011
Spinal involvement is common in Morquio A
100%
85%
% subjects
80%
65%
56%
60%
49%
40%
30%
23%
20%
14%
13%
Cervical cord
compression
T-L cord
compression
0%
Kyphoscoliosis
Odontoid
dysplasia
Lumbar lordosis Cervical spine
instability
Cervical
myelopathy
n = 325 Morquio A subjects (mean age = 14.5 years)
Data based on medical history reviews
MorCAP baseline data
Harmatz et al, Mol Genet Metab, 2013
Spinal disc
disease
Bony anomalies: Dysostosis multiplex
Dens hypoplasia
Platyspondyly
Anterior beaking
Posterior scalloping
Thoracolumbar kyphosis
Solanki et al, J Inherit Metab Dis, 2013
Cervical spine subluxation and instability
Etiology:
– dens hypoplasia
– ligamentous laxity
Atlantoaxial (C1-C2) subluxation:
– ADI > 5 mm or PADI < 14 mm
Instability is present when ADI difference
between flexion/extension views > 2 mm
Risk of cord
compression and
neurological
compromise
especially in
presence of cervical
spinal canal stenosis
Solanki et al, J Inherit Metab Dis, 2013
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 cord compression
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
Early recognition and diagnosis of spinal problems
can minimize morbidity and mortality
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
Image courtesy of Kenneth Martin, MD
Solanki et al, J Inherit Metab Dis, 2013
Neurological examination can identify patients
at early stages of spinal cord compression
Presenting 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
Imaging is critical for risk assessment
and diagnosis of spinal cord compression
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
Images courtesy of Kenneth Martin, MD
Solanki et al, J Inherit Metab Dis, 2013
Clinical and neurological findings should be
correlated with imaging studies
Radiography
Strengths
Limitations
Assess bone malformation
Poor soft tissue discrimination
Assess spinal canal stenosis
Limited by overlapping structures
Assess malalignment
Ionizing radiation
Flexion-extension instability
Limited to ossified structures
Rapid
Inexpensive
Solanki et al, J Inherit Metab Dis, 2013
CT
Strengths
Limitations
Rapid (may obviate need for
anesthesia)
Suboptimal for visualizing soft
tissues and the spinal cord
Multiplanar imaging of bony
structures
Ionizing radiation
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
Solanki et al, J Inherit Metab Dis, 2013
More expensive and less accessible
than plain film radiography
MRI
Strengths
Limitations
Multiplanar imaging
Long imaging times
Ideal for soft tissue imaging
May require anesthesia
Preferred method for assessing
spinal cord compression and
myelomalacia
Metal and motion artifacts
Flexion-extension imaging directly
visualizes spinal cord
Demonstrate venous collaterals
Non-ionizing radiation
Solanki et al, J Inherit Metab Dis, 2013
Limited access
Expensive
MRI is the single most useful tool for
assessing spinal cord compression
MRI sequences:
– T1
– T2
– Cisternography
– CSF Flow
– Diffusion
– Spectroscopy
– MR venography
Myelomalacia is diagnosed by an increase in
T2 signal coupled with volume loss in regions
of cord compression
Solanki et al, J Inherit Metab Dis, 2013
Natural history of cord compression
Normal Cord Function
Normal Cord Function
Normal Cord Function
- Canal stenosis without
contact or compression
- CSF effacement and
cord contact
- Cord compression with
normal T2, diffusivity and
spectroscopy
- Threshold for critical cord compression -
Cord dysfunction, possibly reversible
- Cord compression with normal T2, but
altered diffusivity and spectroscopy
Solanki et al, Mol Genet Metab, 2012
Cord dysfunction, probably arrestable,
may not be reversible
- Cord compression with abnormal T2,
indicating myelomalacia or edema
Regular assessments are recommended
for improved patient outcomes
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)
Yes
2-3 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
Solanki et al, J Inherit Metab Dis, 2013
Preoperative planning
Surgical interventions
Indications include:
– Neurological deficits + instability
– Cord compression with signal change on MRI
Ain et al, Spine, 2006
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
White, Curr Orthop Prac, 2012
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 outcomes
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
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
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.
Airway and anesthetic management of Morquio A
patients presenting for surgery is challenging
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