Background Mucopolysaccharidoses (MPS) represent a group of inheritable lysosomal storage diseases caused by mutations in the genes coding for enzymes involved in catabolism of different glycosaminoglycans (GAGs). They are clinically heterogeneous multisystemic diseases, often involving the spine. Bony abnormalities of the spine included in the so-called dysostosis multiplex and GAG deposits in the dura mater and supporting ligaments can result in spinal cord compression, which can lead to compressive myelopathy. Spinal involvement is a major cause of morbidity and mortality in some MPS (e.g., MPS IVA, VI, and I), and early radiological diagnosis is critical in preventing or arresting neurological deterioration and loss of function. Discussion Management of MPS, however, requires a multidisciplinary approach because of the multiorgan nature of the disease. Indeed in order to appreciate the relevance and nuances of each other's specialty, radiologists and clinicians need to have a background of common knowledge, rather than a merely compartmentalized point of view. In the interest of the management of spinal involvement inMPS, this review article aims on one hand to provide radiologists with important clinical knowledge and on the other hand to equip clinicians with relevant radiological semiotics.

1. Spinal Involvement
in
Mucopolysaccharidoses
Daniele Amato
Scuola di Specializzazione in Radiodiagnostica
Università Cattolica del Sacro Cuore – Roma

2. ü Mucopolysaccharidoses MPS
represent a group on inheritable lysosomial storage disease caused
by mutations in the genes coding for enzymes involved in catabolism
of different glycosaminoglycans GAGs
ü Spinal involvement is a major cause of morbidity and mortality
in some MPS eg MPS IVA VI and I and early radiological diagnosis
is critical in preventing or arresting neurological deterioration and
loss of function
ü Management of MPS requires a multidisciplinary approach
because of the multiorgan nature of the disease
Background

3. Introduction
ü Glycosaminoglycans GAGs or Mucopolysaccharides
ü Dermetan Sulfate
ü Heparan Sulfate
ü Keratan Sulfate
ü Chondroitin Sulfate
ü Hyaluronic Acid
ü Proteoglycans
ü *px*1 a / b

5. Clinical Features
ü Incidence 1/22 000 births
ü Autosomal Recessive
ü Xlinked Recessive MPS II
ü *px*
ü Spinal involvement
ü Bony anomalies
ü Spinal Stenosis
ü Spinal Cord Compression

6. Spinal Involvement
ü GAG deposits in the meninges and supporting ligaments
ü Atlantoaxial subluxation and instability can result in spinal cord
compression with or without signs of compressive myelopathy
ü The thoracolumbar spine and more commonly the craniocervical
junction are the two major locations of spinal cord compression

7. Spinal Involvement
ü *px* fig2

8. Bony Anomalies
ü Early Childhood
ü Oval Shape
ü Anterior Beaking
ü Late Childhood *Pix2*
ü Anterior Beaking
ü Posterior Scalloping
ü Wide Intervertebral disc spaces
ü Adult *Pix2*
ü Flattened Rectangular Shape

9. Bony Anomalies
ü Primary Hypoplasia of the vertebrae ∣ Langer 1966
ü Muscular Hypotonia∣ Swischuk 1970
ü Failure of ossification of the vertebral body ∣ Field et al 1994
ü Mechanical factors on CT and TL junction ∣ Tandon et al 1996
ü Retrolisthesis ∣ Spondylolisthesis
ü Anterior beaking and vb flattening → TL kyphosis / gibbus px2*
ü Incoplete ossification odontoid process → Os odontoideum

10. Bony Anomalies
ü Os odontoideum px4 + icons

11. Spinal Stenosis
ü Diminished space for neural and vascular elements in the spine
ü Focal ∣ single level
ü Central ∣ central spinal canal
ü Lateral ∣ lateral recesses of the central spinal canal
ü Developmental
ü Hereditary/Idiopathic stenosis
ü Disorders of skeletal growth → MPS
ü Acquired Trauma
ü Inflammation/Infection ∣ Vasculopathies ∣ Surgery ∣ Neoplasia

12. Spinal Cord Compression
ü Etiopathigenesis
ü GAG deposits in the periodontoid tissue
ü Vb Anomalies
ü Pix 4*

13. Imaging
ü RX
ü CT
ü MRI
ü Screening
ü Diagnosis → Surgical Intervention
ü Follow up

14. RX
ü Simple
ü Cheap
ü Available
ü AP LL FLEX Px**
ü Suggest / support the diagnosis when MPS suspected
ü Detection / Quantification of gross anomalies
ü Follow up Kyphoscoliosis Px
ü Limits
ü C1/C2 ∣ Basilar invagination and enlarged mastoid process

15. CT
ü Fast Acquisition
ü Anatomical Coverage
ü High Spatial Resolution
ü Isotropic Data Acquition
ü High Diagnostic Accuracy
ü Demonstration of vb bony changes
ü Patients with limited cooperation
ü Presurgical planning

16. CT
ü Spinal Cord Edema *px 4 abcd

17. MRI
ü High Diagnostic Accuracy
ü Evaluation of the complications of MPS
ü central spinal canal stenosis, spinal cord compression, and myelopathy
ü Definition of the need for surgical treatment
ü Monitoring of the pathological progression of the disease
ü ↑ T2w → edema ischemia gliosis/myelomalacia
ü Correlation with signs and symptoms
ü Protocol
ü SE T1w ax/sag
ü FSE T2w ax/sag
ü fMRI → PCI DWI DTI FLEX
ü Limits
ü Cooperation of the patient → children mental retardation

18. Imaging
ü RX
ü CT
ü MRI
ü Screening
ü Diagnosis → Surgical Intervention
ü Follow up
ü Correlation between imaging findings and any type of MPS?

19. ü Correlation between imaging findings and any type of MPS?

20. Diagnosis
ü Clinical Features
ü Urinary GAGs
ü Screening / Diagnosis of MPS subtype
ü Skin Biopsy → Enzymatic Activity Essay
ü Prenatal Molecular Genetic Diagnosis
ü Identification of the gene defect in cultured chorionic villus or
amniotic fluid → X linked Rec

21. Treatment
ü Hematopoietic stem cell tx → MPS I VI VII
ü Intravenous ERT Enzyme Replacement Therapy! → MPS I II VI
ü Other
ü Gene Therapy
ü Intratecal ERT
ü Molecular Therapies
ü Surgery GS!

22. Surgery
ü GS Treatment
ü Spinal cord compression and progressive TL kyphosis
ü Aims:
ü Restore normal vb alignment
ü Protect nerve strx
ü Stabilization
ü Acceptable Spinal Mobility
ü Posterior OccipitoCervical fusion
ü TL spinal cord decompression

23. Conclusion
ü MPS abnormalities are chronic progressive often debilitating and
a major cause of mortality
ü RX / CT / MRI
ü Diagnosis → Surgical Planning → Follow up
ü Early Diagnosis and Timely Treatment
ü Limit → Attenuated disease
ü Correlation of clinical with imaging findings
ü Common knowledge for radiologists and clinicians

24. Grazie per l’attenzione