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Relevance of corpus callosum splenium versus middle cerebellar peduncle hyperintensity for FXTAS diagnosis in clinical practice

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Abstract

Fragile X-associated tremor ataxia syndrome (FXTAS) is caused by FMR1 premutation. The features include ataxia, action tremor and middle cerebellar peduncle (MCP) hyperintensity, the latter being the only major radiological criterion in the diagnosis of definite FXTAS until very recently. The importance of corpus callosum splenium (CCS) hyperintensity was recently reported and this sign is now considered as an additional major radiological diagnostic criterion in the diagnosis of FXTAS. However, little is known about its relevance for the diagnosis of FXTAS in clinical practice. We report a practical justification of the relevance of CCS hyperintensity in parallel with MCP hyperintensity for the diagnosis of FXTAS. Clinical and radiological study of 22 FMR1 premutation carriers with neurological signs that may be encountered in FXTAS compared to series of patients with essential tremor, multiple system atrophy of cerebellar type, Parkinson’s disease, Alzheimer’s disease and stroke. Among the 22 patients with FMR1 premutation [17 men, 5 women; mean age, 63 ± 7.5 (46–84)], 14 were diagnosed with definite FXTAS with the initial criteria. Considering CCS hyperintensity as a new major radiological criterion permitted the diagnosis of definite FXTAS in 3 additional patients. Overall CCS proved as frequent as MCP hyperintensity (64 versus 64 %), while 23 % of patients had CCS but not MCP hyperintensity, 14 % of patients had CCS hyperintensity but neither MCP, nor brainstem hyperintensity. In contrast with CCS hyperintensity, MCP hyperintensity proved less frequent in women than in men. CCS and MCP hyperintensity were more frequent in FXTAS than in the other neurodegenerative disorders. The combination of CCS and MCP hyperintensity was specific of FXTAS. We confirmed the relevance of CCS hyperintensity in FXTAS and we clarified its interest compared to MCP hyperintensity. Our results support the inclusion of CCS hyperintensity in the diagnostic criteria as a new major radiological criterion.

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Conflicts of interest

The final manuscript has been read and approved by all authors who accepted full responsibility for the design and undertaking of the original article, had access to the data and controlled the decision to publish. MA declares conflict of interest with Novartis, Abbvie, TEVA/Lundbeck and Actelion. WM declares conflict of interest with TEVA/Lundbeck, Novartis, UCB, Affiris and GSK. The other authors have no conflict of interest to declare.

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Local ethics committees approved the study and all participants being informed gave written consent.

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Authors and Affiliations

  1. Département de Neurologie, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, 1 Avenue Molière, 67098, Strasbourg Cedex, France

    Mathilde Renaud, Julien Perriard, Jean-Baptiste Chanson, Nicolas Collongues, Nathalie Philippi, Odile Gebus, Véronique Quenardelle, Andoni Echaniz-Laguna, Christine Tranchant & Mathieu Anheim

  2. Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France

    Mathilde Renaud, Julien Perriard, Jean-Baptiste Chanson, Nicolas Collongues, Nathalie Philippi, Odile Gebus, Véronique Quenardelle, Andoni Echaniz-Laguna, Christine Tranchant & Mathieu Anheim

  3. Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM-U964/CNRS-UMR7104/Université de Strasbourg, 67404, Illkirch, France

    Mathilde Renaud, Julien Perriard, Christine Tranchant & Mathieu Anheim

  4. Service de Neurologie, Hôpital Gui de Chauliac, CHU de Montpellier, 34295, Montpellier Cedex, France

    Sarah Coudray & Pierre Labauge

  5. Département de Neurologie, Hôpital Nord Laennec, CHU de Nantes, Boulevard Jacques Monod, Saint Herblain, 44093, Nantes Cedex 1, France

    Mathieu Sévin-Allouet

  6. Département de Neurologie, CH de Saint Malo, 1 rue de la Marne, 35403, Saint-Malo Cedex, France

    Christophe Marcel

  7. Département de Neurologie, Hôpital Haut-Lévêque, CHU de Bordeaux, 1 Avenue Magellan, 33604, Pessac, France

    Wassilios G. Meissner

  8. Institut des Maladies Neurodégénératives, CNRS UMR 5293, Université de Bordeaux, 33000, Bordeaux, France

    Wassilios G. Meissner

  9. Département de Neurologie, CHU de Grenoble, BP 217, 38043, Grenoble Cedex 9, France

    Anna Castrioto & Paul Krack

  10. Département de génétique Médicale, Hôpital d’enfants de la Timone, 264 rue Saint-Pierre, 13385, Marseille Cedex, France

    Karine N’Guyen

  11. Département d’informations médicales, Hôpital Civil, Hôpitaux Universitaires de Strasbourg, 1 place de l’Hôpital, 67000, Strasbourg, France

    François Lefebvre & Nicolas Meyer

  12. Département de Neurologie, Hôpital de la Timone, CHU de Marseille, 13385, Marseille Cedex 5, France

    Jean-Philippe Azulay

Authors
  1. Mathilde Renaud
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  2. Julien Perriard
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  3. Sarah Coudray
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  4. Mathieu Sévin-Allouet
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  5. Christophe Marcel
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  6. Wassilios G. Meissner
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  7. Jean-Baptiste Chanson
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  8. Nicolas Collongues
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  9. Nathalie Philippi
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  10. Odile Gebus
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  11. Véronique Quenardelle
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  12. Anna Castrioto
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  13. Paul Krack
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  14. Karine N’Guyen
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  15. François Lefebvre
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  16. Andoni Echaniz-Laguna
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  17. Jean-Philippe Azulay
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  18. Nicolas Meyer
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  19. Pierre Labauge
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  20. Christine Tranchant
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  21. Mathieu Anheim
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Corresponding author

Correspondence to Mathieu Anheim.

Additional information

M. Renaud and J. Perriard contributed equally to this manuscript and should be considered as first author.

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Renaud, M., Perriard, J., Coudray, S. et al. Relevance of corpus callosum splenium versus middle cerebellar peduncle hyperintensity for FXTAS diagnosis in clinical practice. J Neurol 262, 435–442 (2015). https://doi.org/10.1007/s00415-014-7557-7

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  • DOI: https://doi.org/10.1007/s00415-014-7557-7

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