Spinal involvement in Morquio A

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 deathSolanki 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


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


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


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


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


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 studiesSolanki et al, J Inherit Metab Dis, 2013

Imaging is critical for risk assessment and diagnosis of spinal cord compression

Strengths LimitationsAssess 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


Strengths LimitationsRapid (may obviate need for anesthesia) Multiplanar imaging of bony structuresAlternative 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 radiationMore expensive and less accessible than plain film radiography

CT


Strengths LimitationsMultiplanar 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


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


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 monthsPlain 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 yearFlexion-extension of cervical spine by MRI Yes 1-3 years

CT neutral region of interest Preoperative planning


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

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Spinal involvement in Morquio A