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Brain and spine MRI features of Hunter disease: frequency, natural evolution and response to therapy

  • Original Article
  • Published:
Journal of Inherited Metabolic Disease

Abstract

Backgroud

Hunter disease is a rare X-linked mucopolysaccharidosis. Despite frequent neurological involvement, characterizing the severe phenotype, neuroimaging studies are scarce.

Objectives

To determine frequency and severity of neuroradiological mucopolysaccharidosis-related features; to correlate them with clinical phenotype; to evaluate their natural evolution and the impact of intravenous enzymatic replacement therapy (ERT).

Methods

Sixty nine brain MRI examinations of 36 Italian patients (mean-age 10.4 years; age-range 2.2-30.8; severe phenotype in 22 patients) were evaluated. Twenty patients had multiple MRIs (median follow-up 3.1 years, range 1–16.9): among them 15 had MRIs before and after ERT, six had repeated MRIs without being on ERT and five while on ERT. Perivascular, subarachnoid and ventricle space enlargement, white matter abnormality (WMA) burden, pituitary sella/skull/posterior fossa abnormalities, periodontoid thickening, spinal stenosis, dens hypoplasia, myelopathy, vertebral and intervertebral disc abnormalities were graded by means of dedicated scales.

Results

Perivascular spaces enlargement (89%), WMAs (97%), subarachnoid space enlargement (83%), IIIrd-ventricle dilatation (100%), pituitary sella abnormalities (80%), cranial hyperostosis (19%), craniosynostosis (19%), enlarged cisterna magna (39%), dens hypoplasia (66%), periodontoid thickening (94%), spinal stenosis (46%), platyspondylia (84%) and disc abnormalities (79%) were frequently detected. WMAs, IIIrd-ventricle dilatation and hyperostosis correlated with the severe phenotype (p < 0.05). Subarachnoid spaces and ventricle enlargement, WMAs and spinal stenosis progressed despite ERT, while other MR features showed minimal or no changes.

Conclusions

The spectrum of brain and spine MRI abnormalities in Hunter disease is extremely wide and requires a thorough evaluation. WMAs, atrophy/communicating hydrocephalus and spinal stenosis progress over time and might represent possible disease severity markers for new treatment efficacy assessment.

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Acknowledgment

We acknowledge Fondazione Pierfranco e Luisa Mariani for their consistent economic support to the metabolic Center in Monza.

We acknowledge Frits Wijburg and Chiara Briani for their critical support.

Author information

Authors and Affiliations

  1. Neuroradiologic Unit, University Hospital of Padua, via Giustiniani 2, 35128, Padova, Italy

    Renzo Manara & Rodica Mardari

  2. Centre for Rare Diseases, Department of Pediatrics, University of Padua, Padua, Italy

    Elena Priante, Irene Giovannini, Angelica Rampazzo & Maurizio Scarpa

  3. Neuroradiology Section, Department of Radiology, San Gerardo Hospital, Monza, Italy

    Marco Grimaldi

  4. Metabolic diseases, Institute of Maternal-Infantile Sciences, Polytechnic University of Marche, Ancona, Italy

    Lucia Santoro & Anna Ficcadenti

  5. Department of Pediatrics, Federico II University, Naples, Italy

    Luca Astarita & Simona Fecarotta

  6. Referral centre for inherited metabolic diseases, Department of Pediatrics, University of Catania, Catania, Italy

    Rita Barone & Agata Fiumara

  7. Department of Pediatrics, Magna Graecia University of Catanzaro, Catanzaro, Italy

    Daniela Concolino

  8. Unit of Rare Diseases, Department of Pediatrics, Gaslini Institute Genoa, Genova, Italy

    Maja Di Rocco

  9. Metabolic and Neuromuscular Unit, Meyer Children Hospital, University of Florence, Florence, Italy

    Maria Alice Donati & Elena Procopio

  10. Rare Metabolic Diseases Unit Fondazione Mariani, Pediatric Department, San Gerardo Hospital, Monza, Italy

    Francesca Furlan & Rossella Parini

  11. Department of Biomedical Sciences and Biotechnologies, Cagliari, Italy

    Franco Lilliu & Graziolina Sanna

  12. Radiology Section, Department of Clinical Sciences, Polytechnic University of Marche, Ancona, Italy

    Gabriele Polonara

  13. Pediatric Neuroradiology Department, G. Gaslini Children’s Hospital, Genoa, Italy

    Andrea Rossi

Authors
  1. Renzo Manara
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  2. Elena Priante
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  3. Marco Grimaldi
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  4. Lucia Santoro
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  5. Luca Astarita
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  6. Rita Barone
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  7. Daniela Concolino
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  8. Maja Di Rocco
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  9. Maria Alice Donati
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  10. Simona Fecarotta
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  11. Anna Ficcadenti
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  12. Agata Fiumara
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  13. Francesca Furlan
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  14. Irene Giovannini
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  15. Franco Lilliu
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  16. Rodica Mardari
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  17. Gabriele Polonara
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  18. Elena Procopio
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  19. Angelica Rampazzo
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  20. Andrea Rossi
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  21. Graziolina Sanna
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  22. Rossella Parini
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  23. Maurizio Scarpa
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Corresponding author

Correspondence to Renzo Manara.

Additional information

Communicated by: Ed Wraith

Competing interest: None declared.

Dr. M. Ermani, (Neurology Department, University Hospital of Padua) performed the statistical analysis.

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Manara, R., Priante, E., Grimaldi, M. et al. Brain and spine MRI features of Hunter disease: frequency, natural evolution and response to therapy. J Inherit Metab Dis 34, 763–780 (2011). https://doi.org/10.1007/s10545-011-9317-5

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  • DOI: https://doi.org/10.1007/s10545-011-9317-5

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