Progress and challenges in sporadic late-onset cerebellar ataxias
Nat Rev Neurol. 2025-09-22; :
DOI: 10.1038/s41582-025-01136-0
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https://www.bordeaux-neurocampus.fr/12131
Wirth T(1)(2)(3), Faber J(4)(5), Depienne C(6), Roze E(7), Honnorat J(8)(9),Meissner WG(10)(11)(12)(13), Giunti P(14)(15), Tranchant C(1)(2)(3), KlockgetherT(4)(5), Anheim M(16)(17)(18).
Author information:
(1)Department of Neurology, University Hospital of Strasbourg, Strasbourg,
France.
(2)Strasbourg Neuroscience Institute, Strasbourg University, Strasbourg, France.
(3)Institute of Genetics and Cellular and Molecular Biology, INSERM-U964,
CNRS-UMR7104, University of Strasbourg, Illkirch-Graffenstaden, France.
(4)Center of Neurology, University Hospital Bonn, Bonn, Germany.
(5)German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
(6)Institute of Human Genetics, Essen University Hospital, University of
Duisburg-Essen, Essen, Germany.
(7)Département de Neurologie, Hôpital de la Pitié Salpêtrière, Assistance
Publique-Hôpitaux de Paris, Institut du Cerveau, Sorbonne Universités
INSERM-U1127, CNRS-UMR7225, Paris, France.
(8)French Reference Center on Paraneoplastic Neurological Syndromes and
Autoimmune Encephalitis, Hospices Civils de Lyon, Lyon, France.
(9)MeLiS Institute, INSERM-U1314, CNRS-UMR5284, Université Claude Bernard Lyon
1, Lyon, France.
(10)Centre Hospitalo-Universitaire de Bordeaux, Service de Neurologie – Maladies
Neurodégénératives, Centre de Référence Maladies Rares Atrophie
Multisystématisée, Bordeaux, France.
(11)Institut des Maladies Neurodégénératives Cliniques, Université de Bordeaux,
CNRS-UMR5293, Bordeaux, France.
(12)Department of Medicine, University of Otago, Christchurch, New Zealand.
(13)New Zealand Brain Research Institute, Christchurch, New Zealand.
(14)Ataxia Centre, Department of Clinical and Movement Neurosciences, University
College London (UCL) Queen Square Institute of Neurology, London, UK.
(15)National Hospital for Neurology and Neurosurgery, University College London
Hospitals NHS Foundation Trust, London, UK.
(16)Department of Neurology, University Hospital of Strasbourg, Strasbourg,
France. .
(17)Strasbourg Neuroscience Institute, Strasbourg University, Strasbourg,
France. .
(18)Institute of Genetics and Cellular and Molecular Biology, INSERM-U964,
CNRS-UMR7104, University of Strasbourg, Illkirch-Graffenstaden, France.
.
Sporadic late-onset cerebellar ataxia (SLOCA) is a syndrome defined by subacute
or chronic and progressive ataxia occurring after the age of 40 years in
individuals without a family history of ataxia. The 2022 publication of revised
consensus diagnostic criteria for multiple system atrophy and the emergence of
promising biomarkers provides a thorough diagnostic framework that now enables
the diagnosis of numerous acquired causes of SLOCA, including autoimmune
disorders and neurodegenerative diseases. The ongoing development and increased
availability of DNA sequencing technology have uncovered several molecular
causes of SLOCA besides spastic paraplegia type 7 and very late-onset Friedreich
ataxia. These additional causes include sporadic genetic disorders, such as
spinocerebellar atrophy type 27B, caused by GAA expansion in the FGF14 gene, and
cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS),
caused by biallelic expansions in the RFC1 gene. This Review presents an updated
clinical approach to the diagnosis and management of SLOCA that focuses on the
most important developments in this field. Future challenges are also discussed,
including the identification of additional missing genetic causes of SLOCA,
especially via the use of long-read genome sequencing, improvements in SLOCA
prognostication and the implementation of clinical trials of neuroprotective
interventions.
© 2025. Springer Nature Limited.
DOI: 10.1038/s41582-025-01136-0
PMID: 40983776
Conflict of interest statement: Competing interests: T.W. declares that he has
received honoraria from Abbvie, Edimark and Ipsen; research grants from APTES,
Fondation Planiol, the France Parkinson organizations and Revue Neurologique;
prize money from the Société Française de Neurologie; and travel funding from
Homeperf, Lübeck, LVL Medical and the Movement Disorder Society. C.T. declares
that she has received honoraria from Abbvie, Biogen, Ipsen and Lynde. M.A.
declares that he has received honoraria from Abbvie, Aguettant, Asdia Biogen,
Ever Pharma, Ipsen, Merz, Orkyn, Reata Pharmaceuticals and Teva. The other
authors declare no competing interests.