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Ataxia Associated with CADASIL: a Pathology-Confirmed Case Report and Literature Review

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Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is primarily characterized by migraine, stroke, mood disturbances, and cognitive decline. Ataxia has seldom been reported as a presenting symptom. Here, we review reports of CADASIL presenting as ataxia and compare these to the first pathologically confirmed case of CADASIL presenting with progressive ataxia. A 50-year-old woman presented with progressive truncal ataxia. Brain magnetic resonance imaging (MRI) revealed white matter hyperintensities in the bilateral anterior temporal lobes, external capsules, and periventricular areas, but not the cerebellum. Electron microscopy of skin biopsy material revealed multiple granular osmiophilic materials. Genetic testing confirmed a c.4552C > A mutation in exon 25 of the NOTCH3 gene. CADASIL is a rare cause of progressive ataxia, and only four cases of CADASIL presenting with ataxia have been reported in the literature. We also discuss the possible pathophysiology of cerebellar ataxia associated with CADASIL.

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Funding

This research was partly supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (No. NRF-2017R1C1B5018378 (J.H.Y), NRF-2018M3A9E8023859 (J.H.Y).

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Authors and Affiliations

  1. Department of Neurology, Ajou University School of Medicine, 164, World cup-ro, Yeontong-gu, Suwon-si, Gyeonggi-do, 16499, South Korea

    Don Gueu Park, Je Hong Min & Jung Han Yoon

  2. Laboratory of Cell Biology, Ajou University School of Medicine, Suwon, South Korea

    Seong hyang Sohn

  3. Medical Genetics, Ajou University School of Medicine, Suwon, South Korea

    Young Bae Sohn

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  1. Don Gueu Park
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  2. Je Hong Min
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Contributions

JHY contributed to the study conception and design. Material preparation and data collection were performed by DGP, JHM, SHS, and YBS. The first draft of manuscript was written by DGP and JHY, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Jung Han Yoon.

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

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ESM 1

The patient finds it difficult to rise from a chair and to walk even with assistance. Limb ataxia is evident in finger-to-nose, heel-to-shin, and rapid alternating movement tests. The patient provided written informed consent for publication of this video. (MP4 1995 kb)

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Park, D.G., Min, J.H., Sohn, S.h. et al. Ataxia Associated with CADASIL: a Pathology-Confirmed Case Report and Literature Review. Cerebellum 19, 907–910 (2020). https://doi.org/10.1007/s12311-020-01173-z

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  • DOI: https://doi.org/10.1007/s12311-020-01173-z

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