Spinal involvement in Morquio A - PowerPoint Presentation

Slide1

Spinal involvement in Morquio A Slide2

Atlantoaxial system: anatomy and pathology

Articulation of C1 (atlas) with C2 (axis) is complex, comprising several joints

Median atlantoaxial jointTwo lateral atlantoaxial joints These joints are held in place and supported by several ligamentsMajor stabilizing ligaments are the transverse and alar ligamentsIncompetent 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 failureVertical 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) Slide3

Top image courtesy of Michael Beck, MD, and Christina Lampe, MD

Bottom image courtesy of Christina Lampe, MD

Spinal involvement is a major cause of morbidity and mortality in Morquio A SyndromeSpectrum of spinal involvement:Bony anomaliesCervical spine subluxation and instabilitySpinal canal stenosisSpinal cord compression Spinal problems predispose patients to myelopathy, paralysis, and premature deathSolanki et al, J Inherit Metab Dis, 2013; Montano et al, J Inherit Metab Dis, 2007; Tomatsu et al, Curr Pharm Biotechnol, 2011Slide4

Harmatz et al

, Mol Genet Metab

, 2013MorCAP baseline dataSpinal involvement is common in Morquio An = 325 Morquio A subjects (mean age = 14.5 years)Data based on medical history reviewsSlide5

Dens hypoplasia

PlatyspondylyAnterior beakingPosterior scalloping Thoracolumbar kyphosisSolanki et al, J Inherit Metab Dis, 2013Bony anomalies: Dysostosis multiplexSlide6

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 mmSolanki et al, J Inherit Metab Dis, 2013Cervical spine subluxation and instability Risk of cord compression and neurological compromise especially in presence of cervical spinal canal stenosisSlide7

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-L1Focal stenosis:CCJ: thickening of the membrana tectoria and apical and occipito-atlantal ligamentsC1-C2: thickening of the peri-odontoid tissue and transverse atlantoaxial ligament + C1 posterior archC3-C7: bulging discsThoracolumbar and upper thoracic spine: kyphosisSolanki et al, J Inherit Metab Dis, 2013Spinal canal stenosisSlide8

Etiology:

Thickened ligaments

Cervical instabilityCartilaginous and ligamentous hypertrophy at the C1-C2 jointSpinal canal stenosisDisc protrusionKyphosisSpinal 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 compressionUntreated cord compression can lead to cord damage and myelopathySolanki et al, J Inherit Metab Dis, 2013Spinal cord compression Slide9

Image courtesy of Kenneth Martin, MD

Diagnostic and monitoring tools:

Neurological examinationImagingRadiographyComputed tomography (CT)Magnetic resonance imaging (MRI)Other diagnostic examinationsFunctional testing (e.g. 6 minute walk test)Sleep studiesUrodynamics Solanki et al, J Inherit Metab Dis, 2013Early recognition and diagnosis of spinal problems can minimize morbidity and mortality Slide10

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 involvementneurological signs and symptoms may underestimate the severity of spinal cord compression seen on MRIdetermination of the responsible level is challenging in patients with multi-segmental myelopathySolanki et al, J Inherit Metab Dis, 2013Slide11

Images courtesy of Kenneth Martin, MD

Goals of imaging:

Detect treatable spinal cord compressionStratify risk to spinal cord prior to permanent loss of functionAssist in surgical planningAssess efficacy of surgical and medical treatmentSystematic and careful imaging involves:Plain radiography, including instability imagingMRI of the spinal cordCT may be requiredClinical and neurological findings should be correlated with imaging studiesSolanki et al, J Inherit Metab Dis, 2013Imaging is critical for risk assessment and diagnosis of spinal cord compressionSlide12

Strengths

Limitations

Assess bone malformationAssess spinal canal stenosisAssess 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

, 2013Slide13

Strengths

Limitations

Rapid (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 radiation

More expensive and less accessible than plain film radiography

CT

Solanki

et al,

J Inherit

Metab

Dis

, 2013Slide14

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

, 2013Slide15

Myelomalacia

is diagnosed by an increase in T2 signal coupled with volume loss in regions of cord compressionMRI sequences:T1T2CisternographyCSF FlowDiffusionSpectroscopyMR venographySolanki et al, J Inherit Metab Dis, 2013MRI is the single most useful tool for assessing spinal cord compressionSlide16

Natural history of cord compression

Solanki

et al, Mol Genet Metab, 2012 - Threshold for critical cord compression - Slide17

Assessment

At diagnosis

FrequencyNeurological 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

Preoperative planning

Solanki et al,

J Inherit

Metab

Dis

, 2013

Regular assessments are recommended

for improved patient outcomesSlide18

White

, Curr Orthop Prac

, 2012Ain et al, Spine, 2006Indications include:Neurological deficits + instabilityCord compression with signal change on MRICervical spine:Posterior fusion for C1-C2 subluxation and instability, often with posterior occipito-cervical fixationIf subluxation is irreducible and cord compression is present, decompression + fusion is indicatedProphylatic fusion recommended by someThoracolumbar kyphosis:Decompression, segmental instrumentation and fusionAnterior discectomy and fusion strongly recommended to augment posterior fusion in cases of rigid kyphosisSolanki 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 interventionsSlide19

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, 2009Short-term post-operative outcomes generally goodPossible post-surgical complications:Late instability below fusion site may necessitate multiple fusions Halo pin tract infection → Long-term monitoring is importantLong-term outcomes beyond 5 years are less known – few studiesSolanki 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 outcomesSlide20

Morquio

A patients are at high risk of anesthesia-related morbidity and mortality due to:

Cervical instability and myelopathyCompromised respiratory functionUpper and lower airway obstructionRestrictive lung diseaseCardiac abnormalitiesAny elective surgery requires:Thorough pre-operative ENT, pulmonary and cardiac evaluationsPre-operative radiological evaluation of the cervical spine Skilled personnel in airway managementSpectrum of airway management equipment Morquio A patients should be managed by experienced anesthesiologists at centers familiar with MPS disordersTheroux 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