Evidence map›Paper›PMID 32040566›Full record

ArticleBrain : a journal of neurology2020

Cerebellar ataxia, neuropathy, vestibular areflexia syndrome due to RFC1 repeat expansion.

Andrea Cortese, Stefano Tozza, Wai Yan Yau, Salvatore Rossi, Sarah J Beecroft, Zane Jaunmuktane, Zoe Dyer, Gianina Ravenscroft, Phillipa J Lamont, Stuart Mossman and 32 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain : a journal of neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
124citing papers in PubMed, 3 pooled it
14.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

124 citing papers in PubMed, 3 syntheses or guidelines pooled it, 217 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Observational
  10. Article
  11. Review
  12. Corticospinal conduction in RFC1-related disease: a transcranial magnetic stimulation study.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
    Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article

64 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

42 authors at 17 institutions in 8 countries.

Andrea CorteseDepartment of Neuromuscular Disease, UCL Queen Square Institute of Neurology and The National Hospital for Neurology, London, UK.
Stefano TozzaDepartment of Neuromuscular Disease, UCL Queen Square Institute of Neurology and The National Hospital for Neurology, London, UK.
Wai Yan YauDepartment of Neuromuscular Disease, UCL Queen Square Institute of Neurology and The National Hospital for Neurology, London, UK.
Salvatore RossiDepartment of Neuromuscular Disease, UCL Queen Square Institute of Neurology and The National Hospital for Neurology, London, UK.
Sarah J BeecroftCentre for Medical Research University of Western Australia, Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, Western Australia 6009, Australia.
Zane JaunmuktaneDepartment of Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology and The National Hospital for Neurology, London, UK.
Zoe DyerAuckland District Health Board (ADHB), Auckland, New Zealand; Centre of Brain Research Neurogenetics Research Clinic, University of Auckland, New Zealand.
Gianina RavenscroftCentre for Medical Research University of Western Australia, Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, Western Australia 6009, Australia.
Phillipa J LamontNeurogenetic Unit, Royal Perth Hospital, Perth, West Australia, Australia.
Stuart MossmanDepartment of Neurology, Wellington Hospital, Wellington 6021, New Zealand.
Andrew ChancellorDepartment of Neurology, Tauranga Hospital, Private Bag, Cameron Road, Tauranga 3171, New Zealand.
Thierry MaisonobeSorbonne Université, AP-HP, Hôpital Pitié-Salpêtrière, Department of Neurophysiology, Paris France.
Yann PereonCHU Nantes, Reference Centre for Neuromuscular Diseases, Hôtel-Dieu, Nantes, France.
Cecile CauquilDepartment of Neurology, CHU Bicêtre, AP-HP, Le Kremlin-Bicêtre, France.
Silvia ColnaghiIRCCS Mondino Foundation, Pavia, Italy.
Giulia MallucciIRCCS Mondino Foundation, Pavia, Italy.
Riccardo CurroDepartment of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
Pedro J TomaselliDepartment of Neurology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
Gilbert Thomas-BlackDepartment of Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology and The National Hospital for Neurology, London, UK.
Roisin SullivanDepartment of Neuromuscular Disease, UCL Queen Square Institute of Neurology and The National Hospital for Neurology, London, UK.
Stephanie EfthymiouDepartment of Neuromuscular Disease, UCL Queen Square Institute of Neurology and The National Hospital for Neurology, London, UK.
Alexander M RossorDepartment of Neuromuscular Disease, UCL Queen Square Institute of Neurology and The National Hospital for Neurology, London, UK.
Matilde LauráDepartment of Neuromuscular Disease, UCL Queen Square Institute of Neurology and The National Hospital for Neurology, London, UK.
Menelaos PipisDepartment of Neuromuscular Disease, UCL Queen Square Institute of Neurology and The National Hospital for Neurology, London, UK.
Alejandro HorgaDepartment of Neuromuscular Disease, UCL Queen Square Institute of Neurology and The National Hospital for Neurology, London, UK.
James PolkeDepartment of Neuromuscular Disease, UCL Queen Square Institute of Neurology and The National Hospital for Neurology, London, UK.
Diego KaskiDepartment of Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology and The National Hospital for Neurology, London, UK.
Rita HorvathDepartment of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
Patrick F ChinneryDepartment of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
Wilson MarquesDepartment of Neurology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
Cristina TassorelliDepartment of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
Grazia DevigiliUO Neurologia I, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milano, Italy.
Lea LeonardisDivision of Neurology, Institute of Clinical Neurophysiology, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Nick W WoodDepartment of Neuromuscular Disease, UCL Queen Square Institute of Neurology and The National Hospital for Neurology, London, UK.
Adolfo BronsteinDepartment of Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology and The National Hospital for Neurology, London, UK.
Paola GiuntiDepartment of Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology and The National Hospital for Neurology, London, UK.
Stephan ZüchnerDr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Tanya StojkovicSorbonne Université, AP-HP, Hôpital Pitié-Salpêtrière, Centre de Référence des Maladies Neuromusculaires, Nord/Est/Ile-de-France, Inserm UMR_S 974, Paris, France.
Nigel LaingCentre for Medical Research University of Western Australia, Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, Western Australia 6009, Australia.
Richard H RoxburghAuckland District Health Board (ADHB), Auckland, New Zealand; Centre of Brain Research Neurogenetics Research Clinic, University of Auckland, New Zealand.
Henry HouldenDepartment of Neuromuscular Disease, UCL Queen Square Institute of Neurology and The National Hospital for Neurology, London, UK.
Mary M ReillyDepartment of Neuromuscular Disease, UCL Queen Square Institute of Neurology and The National Hospital for Neurology, London, UK.
National Hospital for Neurology and Neurosurgery · GBThe University of Western Australia · AUUniversity of Pavia · ITUniversidade de São Paulo · BRUniversity of Auckland · NZUniversity of Cambridge · GBAssistance Publique – Hôpitaux de Paris · FRCentre d'Investigation Clinique de Nantes · FRFondazione IRCCS Istituto Neurologico Carlo Besta · ITInserm · FRLjubljana University Medical Centre · SIRoyal Perth Hospital · AUSorbonne Université · FRTauranga Hospital · NZUniversità Cattolica del Sacro Cuore · ITUniversity of Miami · USWellington Hospital · NZ

Funding

trainingU54NS065712 · NINDS · WAYNE STATE UNIVERSITY · PI SHY, MICHAEL E. · 2009 to 2023
$19.6M
European Research Council 309548Medical Research Council G0601943Medical Research Council G1000848Medical Research Council MC_UU_00015/7Medical Research Council MC_UU_00015/9Medical Research Council MR/N010035/1Medical Research Council MR/N025431/1Medical Research Council MR/N025431/2Medical Research Council MR/S01165X/1Medical Research Council MR/T001712/1NINDS NIH HHS U54 NS065712Wellcome Trust 203148/Z/16/ZWellcome Trust 206675/Z/17/ZWellcome Trust 212219/Z/18/Z
6 · The paper itself

Abstract

Ataxia, causing imbalance, dizziness and falls, is a leading cause of neurological disability. We have recently identified a biallelic intronic AAGGG repeat expansion in replication factor complex subunit 1 (RFC1) as the cause of cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) and a major cause of late onset ataxia. Here we describe the full spectrum of the disease phenotype in our first 100 genetically confirmed carriers of biallelic repeat expansions in RFC1 and identify the sensory neuropathy as a common feature in all cases to date. All patients were Caucasian and half were sporadic. Patients typically reported progressive unsteadiness starting in the sixth decade. A dry spasmodic cough was also frequently associated and often preceded by decades the onset of walking difficulty. Sensory symptoms, oscillopsia, dysautonomia and dysarthria were also variably associated. The disease seems to follow a pattern of spatial progression from the early involvement of sensory neurons, to the later appearance of vestibular and cerebellar dysfunction. Half of the patients needed walking aids after 10 years of disease duration and a quarter were wheelchair dependent after 15 years. Overall, two-thirds of cases had full CANVAS. Sensory neuropathy was the only manifestation in 15 patients. Sixteen patients additionally showed cerebellar involvement, and six showed vestibular involvement. The disease is very likely to be underdiagnosed. Repeat expansion in RFC1 should be considered in all cases of sensory ataxic neuropathy, particularly, but not only, if cerebellar dysfunction, vestibular involvement and cough coexist.

Indexed as

AgedAged, 80 and overAtaxiaCerebellar AtaxiaCerebellumFemaleHumansMaleMiddle AgedNeurologic ExaminationPeripheral Nervous System DiseasesReflex, AbnormalSensation DisordersSyndromeVestibular Neuronitiscerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS)chronic coughrepeat expansionRFC1sensory neuropathy

Identifiers

PMID32040566
PMCPMC7009469
OpenAlexW3005188864

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.