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Spinal involvement in pediatric familial cavernous malformation syndrome

  • Paediatric Neuroradiology
  • Published:
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Abstract

Purpose

The aim of the study was to assess the prevalence and characteristics of spinal cord cavernous malformations (SCCM) and intraosseous spinal vascular malformations (ISVM) in a pediatric familial cerebral cavernous malformation (FCCM) cohort and evaluate clinico-radiological differences between children with (SCCM +) and without (SCCM-) SCCM.

Methods

All patients with a pediatric diagnosis of FCCM evaluated at three tertiary pediatric hospitals between January 2010 and August 2021 with \(\ge\) 1 whole spine MR available were included. Brain and spine MR studies were retrospectively evaluated, and clinical and genetic data collected. Comparisons between SCCM + and SCCM- groups were performed using student-t/Mann–Whitney or Fisher exact tests, as appropriate.

Results

Thirty-one children (55% boys) were included. Baseline spine MR was performed (mean age = 9.7 years) following clinical manifestations in one subject (3%) and as a screening strategy in the remainder. Six SCCM were detected in five patients (16%), in the cervico-medullary junction (n = 1), cervical (n = 3), and high thoracic (n = 2) regions, with one appearing during follow-up. A tendency towards an older age at first spine MR (P = 0.14) and \(\ge\) 1 posterior fossa lesion (P = 0.13) was observed in SCCM + patients, lacking statistical significance. No subject demonstrated ISVM.

Conclusion

Although rarely symptomatic, SCCM can be detected in up to 16% of pediatric FCCM patients using diverse spine MR protocols and may appear de novo. ISVM were instead absent in our cohort. Given the relative commonality of asymptomatic SCCM, serial screening spine MR should be considered in FCCM starting in childhood.

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Abbreviations

CM:

Cavernous malformation

FCCM:

Familial cerebral cavernous malformation syndrome

ISVM:

Intraosseous spinal vascular malformations

SCCM:

Spinal cord cavernous malformation

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Funding

Twelve months research fellowship in diagnostic neuroradiology, European Society of Neuroradiology (AF Geraldo).

Author information

Authors and Affiliations

  1. Diagnostic Neuroradiology Unit, Department of Radiology, Centro Hospitalar Vila Nova de Gaia/Espinho (CHVNG/E), Vila Nova de Gaia, Portugal

    Ana Filipa Geraldo

  2. Clínica Universitária de Imagiologia, Faculty of Medicine of the University of Lisbon, Lisbon, Portugal

    Ana Filipa Geraldo & Sofia Reimão

  3. Department of Radiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK

    Aysha Luis & Kshitij Mankad

  4. Department of Radiology, King’s College London, London, UK

    Aysha Luis

  5. Department of Radiology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Cesar Augusto P. F. Alves & Erin Simon Schwartz

  6. Neuroradiology Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy

    Domenico Tortora, Andrea Rossi & Mariasavina Severino

  7. Department of Neurology, Centro Hospitalar Universitário de São João, Porto, Portugal

    Joana Guimarães

  8. Department of Clinical Neusosciences and Mental Health, Faculty of Medicine of the University of Porto, Porto, Portugal

    Joana Guimarães

  9. Neuroimaging department, Hospital de Santa Maria, Lisbon, Portugal

    Sofia Reimão

  10. Neurosurgery Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy

    Marco Pavanello

  11. Medical Genetics Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy

    Patrizia de Marco & Valeria Capra

  12. Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy

    Marcello Scala

  13. Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy

    Marcello Scala

  14. Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy

    Andrea Rossi

Authors
  1. Ana Filipa Geraldo
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  2. Aysha Luis
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  3. Cesar Augusto P. F. Alves
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  4. Domenico Tortora
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  5. Joana Guimarães
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  6. Sofia Reimão
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  7. Marco Pavanello
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  8. Patrizia de Marco
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  9. Marcello Scala
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  10. Valeria Capra
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  11. Andrea Rossi
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  12. Erin Simon Schwartz
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  13. Kshitij Mankad
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  14. Mariasavina Severino
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Contributions

AF Geraldo, S Reimao, Severino M: study concept and design. AF Geraldo, A Luis, CAPF Alves, D Tortora, E S Shwartz, K Mankad, A Rossi, M Severino: analysis and interpretation of imaging data. AF Geraldo: statistical analysis. AF Geraldo: drafting the manuscript. AF Geraldo, A Luis, CAPFAlves, D Tortora, J Guimarães, S Reimão, A Rossi, M Pavanello, P De Marco, M Scala, V Capra, Rossi A, E S Shwartz, K Mankad, M Severino: revising the manuscript.

Corresponding author

Correspondence to Andrea Rossi.

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Ethics approval

All procedures performed in studies involving human participants were in accordance with ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

For this type of study, formal consent is not required.

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The authors declare no competing interests.

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Supplementary Information

Below is the link to the electronic supplementary material.

234_2022_2958_MOESM1_ESM.png

Supplementary file1 Supplemental Figure 1. Spine MR (a–e) performed in a 10-year-old boy with familial cerebral cavernous malformation syndrome due to a proven CCM1 mutation (SCCM patient #1) including sagittal T2 TSE (a), T1 TSE (b), and GRE (c) as well as axial T2 TSE (d) and GRE (e) demonstrates an intramedullary cavernous malformation located posteriorly and lateralized to the right at the level of T1-T2 (white arrowheads and empty white arrows). Note the absence of hypointense T2 rim, spinal cord expansion, or edema (PNG 1100 KB)

234_2022_2958_MOESM2_ESM.png

Supplementary file2 Supplemental Figure 2. Follow-up spine MR studies of the same patient presented in Supplemental Figure 1 (SCCM patient #1) performed 7 (a,b) and 36 (c,d) months after including sagittal T2 TSE (a,c) and GRE (b,d) reveal initial subtle growth of the spinal cord cavernous malformation (white arrowheads and empty white arrows) and mild perilesional edema (white thin arrows) followed by size reduction and development of adjacent intramedullary flame-like hemorrhage (thick white arrows). Brain MR obtained at the time of the initial diagnosis including axial SWI (e,f) images reveals two intracranial cavernous malformations, one in the left parietal lobe (black arrowhead) and another in the ipsilateral mesial-temporal region (thin black arrow) (PNG 1153 KB)

Supplementary file3 (DOCX 34 KB)

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Geraldo, A.F., Luis, A., Alves, C.A.P.F. et al. Spinal involvement in pediatric familial cavernous malformation syndrome. Neuroradiology 64, 1671–1679 (2022). https://doi.org/10.1007/s00234-022-02958-1

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  • DOI: https://doi.org/10.1007/s00234-022-02958-1

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