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Imaging features in conventional MRI, spectroscopy and diffusion weighted images of hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS)

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Abstract

Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is a rare autosomal dominant disease caused by mutations within the colony stimulating factor 1 receptor (CSF1R) gene. While a small number of reports on imaging findings in routine MRI exist, reported imaging findings in DWI and spectroscopy are scarce, and limited to not genetically proven case reports. We assessed MRI including DWI and MR spectroscopy in six patients with HDLS and two asymptomatic mutation carriers. A total of 13 MRIs were evaluated and a score of the white-matter lesion (WML) load was calculated. The course of MR abnormalities was followed for 6–19 months in four patients and 95 months in one carrier. MRI revealed widespread white-matter lesions of patchy or confluent pattern especially in the frontal and occipital lobe. The pyramidal tract was less affected than the surrounding tissue in all symptomatic patients on conventional T2WI. Three of four cases with DWI showed small dots of diffusion restriction within WML. Spectroscopy showed increased levels of mIns, Cho and lactate while NAA was decreased. Asymptomatic mutation carriers had, for the age of the patients, unusually pronounced unspecific WMLs. No diffusion restriction or alterations in metabolite levels could be detected in asymptomatic mutation carriers. Microbleeds were not found in any patient. Diffusion restriction seems to be a typical imaging pattern visible in patients with active disease progression in HDLS. Spectroscopic findings and the absence of microbleeds differ clearly from reported findings in CADASIL and subcortical arteriosclerotic encephalopathy. While the distribution and character of WMLs in asymptomatic cases remain unspecific they are likely to represent subclinical markers of HDLS.

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Acknowledgments

The authors wish to thank Chris Nawrat for editing the manuscript for British grammar and punctuation.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical standard

The study was approved by the local institutional review board and written informed consent was obtained from all patients.

Author information

Authors and Affiliations

  1. Department of Diagnostic and Interventional Neuroradiology, MR Research Group, University Hospital Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany

    Benjamin Bender, Uwe Klose, Tobias Lindig & Thomas Nägele

  2. Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research and Department of Neurology, Hoppe-Seyler-Straße 3, 72076, Tübingen, Germany

    Saskia Biskup, Ludger Schöls & Kathrin N. Karle

  3. German Research Center for Neurodegenerative Diseases (DZNE), 72076, Tübingen, Germany

    Saskia Biskup, Ludger Schöls & Kathrin N. Karle

  4. CeGaT GmbH, Center for Genomics and Transcriptomics, Paul-Ehrlich-Str. 17, 72076, Tübingen, Germany

    Saskia Biskup

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  1. Benjamin Bender
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  2. Uwe Klose
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  3. Tobias Lindig
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Corresponding author

Correspondence to Benjamin Bender.

Electronic supplementary material

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415_2014_7509_MOESM1_ESM.tif

Online resource 1: Increased lesion load and progressive atrophy in HDLS after 14 months. Two sagital T2-weighted slices of the same patient (Nr. 6) with a time interval of 14 months (initial scan left side, control scan right side). There is a progressive atrophy pronounced in the corpus callosum, less prominent in the frontal lobe. The patchy areas of hyperintense signal in the frontal and parietal lobe are more confluent in the follow-up scan (TIFF 3130 kb)

415_2014_7509_MOESM2_ESM.tif

Online resource 2: Typical lesion distribution in HDLS and CADASIL. A typical case of HDLS (bottom row) in comparison to a typical case of CADASIL (top row). WML are not found within the temporal lobe and the region of the basal ganglia in this case of HDLS, typical involvement of the capsula externa and the temporal pole is seen in CADASIL. A mild atrophy of the frontal lobe is present in HDLS but no atrophy is seen in CADASIL (TIFF 2782 kb)

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Bender, B., Klose, U., Lindig, T. et al. Imaging features in conventional MRI, spectroscopy and diffusion weighted images of hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS). J Neurol 261, 2351–2359 (2014). https://doi.org/10.1007/s00415-014-7509-2

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  • DOI: https://doi.org/10.1007/s00415-014-7509-2

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