Skip to main content

Advertisement

SpringerLink
Log in

Radiological correlates of episodes of acute decline in the leukodystrophy vanishing white matter

  • Paediatric Neuroradiology
  • Published:
Neuroradiology Aims and scope Submit manuscript

Abstract

Purpose

Patients with vanishing white matter (VWM) experience unremitting chronic neurological decline and stress-provoked episodes of rapid, partially reversible decline. Cerebral white matter abnormalities are progressive, without improvement, and are therefore unlikely to be related to the episodes. We determined which radiological findings are related to episodic decline.

Methods

MRI scans of VWM patients were retrospectively analyzed. Patients were grouped into A (never episodes) and B (episodes). Signal abnormalities outside the cerebral white matter were rated as absent, mild, or severe. A sum score was developed with abnormalities only seen in group B. The temporal relationship between signal abnormalities and episodes was determined by subdividing scans into those made before, less than 3 months after, and more than 3 months after onset of an episode.

Results

Five hundred forty-three examinations of 298 patients were analyzed. Mild and severe signal abnormalities in the caudate nucleus, putamen, globus pallidus, thalamus, midbrain, medulla oblongata, and severe signal abnormalities in the pons were only seen in group B. The sum score, constructed with these abnormalities, depended on the timing of the scan (χ2(2, 400) = 22.8; p < .001): it was least often abnormal before, most often abnormal with the highest value shortly after, and lower longer than 3 months after an episode.

Conclusion

In VWM, signal abnormalities in brainstem, thalamus, and basal ganglia are related to episodic decline and can improve. Knowledge of the natural MRI history in VWM is important for clinical interpretation of MRI findings and crucial in therapy trials.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Abbreviations

IQR:

Interquartile range

VWM:

Vanishing white matter

References

  1. Leegwater PA, Vermeulen G, Konst AA, Naidu S, Mulders J, Visser A et al (2001) Subunits of the translation initiation factor eIF2B are mutant in leukoencephalopathy with vanishing white matter. Nat Genet 29(4):383–388

    Article  CAS  PubMed  Google Scholar 

  2. van der Knaap MS, Leegwater PA, Konst AA, Visser A, Naidu S, Oudejans CB et al (2002) Mutations in each of the five subunits of translation initiation factor eIF2B can cause leukoencephalopathy with vanishing white matter. Ann Neurol 51(2):264–270

    Article  PubMed  Google Scholar 

  3. Hamilton EMC, van der Lei HDW, Vermeulen G, Gerver JAM, Lourenco CM, Naidu S et al (2018) Natural history of vanishing white matter. Ann Neurol 84(2):274–288

    Article  PubMed  PubMed Central  Google Scholar 

  4. van der Knaap MS, Pronk JC, Scheper GC (2006) Vanishing white matter disease. Lancet Neurol 5(5):413–423

    Article  PubMed  Google Scholar 

  5. Bugiani M, Boor I, van Kollenburg B, Postma N, Polder E, van Berkel C et al (2011) Defective glial maturation in vanishing white matter disease. J Neuropathol Exp Neurol 70(1):69–82

    Article  PubMed  Google Scholar 

  6. Stellingwerff MD, Al-Saady ML, van de Brug T, Barkhof F, Pouwels PJW, van der Knaap MS (2021) MRI Natural History of the Leukodystrophy Vanishing White Matter. Radiology 300(3):671–680. https://doi.org/10.1148/radiol.2021210110

    Article  PubMed  Google Scholar 

  7. van der Knaap MS, Breiter SN, Naidu S, Hart AA, Valk J (1999) Defining and categorizing leukoencephalopathies of unknown origin: MR imaging approach. Radiology 213(1):121–133

    Article  PubMed  Google Scholar 

  8. Hanefeld F, Holzbach U, Kruse B, Wilichowski E, Christen HJ, Frahm J (1993) Diffuse white matter disease in three children: an encephalopathy with unique features on magnetic resonance imaging and proton magnetic resonance spectroscopy. Neuropediatrics 24(5):244–248

    Article  CAS  PubMed  Google Scholar 

  9. Tedeschi G, Schiffmann R, Barton NW, Shih HH, Gospe SM Jr, Brady RO et al (1995) Proton magnetic resonance spectroscopic imaging in childhood ataxia with diffuse central nervous system hypomyelination. Neurology 45(8):1526–1532

    Article  CAS  PubMed  Google Scholar 

  10. van der Knaap MS, Barth PG, Gabreels FJ, Franzoni E, Begeer JH, Stroink H et al (1997) A new leukoencephalopathy with vanishing white matter. Neurology 48(4):845–855

    Article  PubMed  Google Scholar 

  11. van der Knaap MS, Kamphorst W, Barth PG, Kraaijeveld CL, Gut E, Valk J (1998) Phenotypic variation in leukoencephalopathy with vanishing white matter. Neurology 51(2):540–547

    Article  PubMed  Google Scholar 

  12. Alorainy IA, Patenaude YG, O’Gorman AM, Black DN, Meagher-Villemure K (1999) Cree leukoencephalopathy: neuroimaging findings. Radiology 213(2):400–406

    Article  CAS  PubMed  Google Scholar 

  13. Bugiani M, Postma N, Polder E, Dieleman N, Scheffer PG, Sim FJ et al (2013) Hyaluronan accumulation and arrested oligodendrocyte progenitor maturation in vanishing white matter disease. Brain 136(Pt 1):209–222

    Article  PubMed  Google Scholar 

  14. Bruck W, Herms J, Brockmann K, Schulz-Schaeffer W, Hanefeld F (2001) Myelinopathia centralis diffusa (vanishing white matter disease): evidence of apoptotic oligodendrocyte degeneration in early lesion development. Ann Neurol 50(4):532–536

    Article  CAS  PubMed  Google Scholar 

  15. Rodriguez D, Gelot A, dellaGaspera B, Robain O, Ponsot G, Sarlieve LL et al (1999) Increased density of oligodendrocytes in childhood ataxia with diffuse central hypomyelination (CACH) syndrome: neuropathological and biochemical study of two cases. Acta Neuropathol. 97(5):469–80

    Article  CAS  PubMed  Google Scholar 

  16. Jacobson S, Marcus EM, Pugsley S. (2018) Myelin-Stained. Neuroanatomy for the Neuroscientist. Cham: Springer International Publishing; 679–89

  17. Dooves S, Bugiani M, Postma NL, Polder E, Land N, Horan ST et al (2016) Astrocytes are central in the pathomechanisms of vanishing white matter. J Clin Invest 126(4):1512–1524

    Article  PubMed  PubMed Central  Google Scholar 

  18. Bugiani M, Plug BC, Man JHK, Breur M, van der Knaap MS (2022) Heterogeneity of white matter astrocytes in the human brain. Acta Neuropathol 143(2):159–177

    Article  PubMed  Google Scholar 

  19. van der Lei HD, Steenweg ME, Barkhof F, de Grauw T, d’Hooghe M, Morton R et al (2012) Characteristics of early MRI in children and adolescents with vanishing white matter. Neuropediatrics 43(1):22–26

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank all referring physicians and IT staff for technical support in digitizing radiologic films. MSvdK is a member of the European reference network for rare neurological disorders (ERN-RND), project ID 739510.

Funding

Not applicable.

Author information

Authors and Affiliations

  1. Department of Child Neurology, Amsterdam Leukodystrophy Center, Emma Children’s Hospital, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam and Amsterdam Neuroscience, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands

    Menno D. Stellingwerff & Marjo S. van der Knaap

  2. Department of Epidemiology and Data Science, and Amsterdam School of Public Health, Amsterdam University Medical Centers, Amsterdam, The Netherlands

    Mark A. van de Wiel

  3. MRC Biostatistics Unit, University of Cambridge, Cambridge, UK

    Mark A. van de Wiel

  4. Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, VU University, Amsterdam, The Netherlands

    Marjo S. van der Knaap

Authors
  1. Menno D. Stellingwerff
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mark A. van de Wiel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marjo S. van der Knaap
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marjo S. van der Knaap.

Ethics declarations

Conflict of interest

MSvdK receives research funding from NWO (Spinoza award), ZonMw (TOP 91217006 and 10140261910004/80–86600-98–84001), Hersenstichting (DR-2019–00285), and European Leukodystrophy Foundation (2019-P001 and 2020-017I2). She has a patent P112686CA00, therapeutic effects of Guanabenz treatment in vanishing white matter, pending to VU University Medical Center. MDS and MAvdW declare no competing interests.

Ethics approval

The local ethics committee approved this retrospective study.

Informed consent

Informed consent was obtained from patients and/or parents.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Stellingwerff, M.D., van de Wiel, M.A. & van der Knaap, M.S. Radiological correlates of episodes of acute decline in the leukodystrophy vanishing white matter. Neuroradiology 65, 855–863 (2023). https://doi.org/10.1007/s00234-022-03097-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00234-022-03097-3

Keywords

Search

Navigation