Clinical trial NCT05278091: Evaluation of the Diagnostic Value of Video-oculography in CANVAS Neuronopathies
Official title: Evaluation of the Diagnostic Value of Video-oculography in CANVAS (Cerebellar Ataxia With Neuropathy and Vestibular Areflexia Syndrome) Neuronopathies
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cerebellar Ataxia
Lead sponsor: Centre Hospitalier Universitaire de Nīmes
Sponsor class: OTHER
First posted: 2022-03-14
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients followed at the CHU of Nîmes between 2018-2021, with a diagnosis of CANVAS with several control groups constituted by patients with a neuropathy of different etiology (a first control group with axonal neuropathies and thus no ataxia in the foreground, a second group with ataxiating neuropathies : (anti-MAG neuropathy, neuronopathies of autoimmune origin) and a healthy control group without neuropathy).

Brief summary: Cerebellar ataxia syndrome with neuropathy and vestibular areflexia (CANVAS) is a genetic pathology of recent discovery (bi-allelic expansion in intron 1 of the RFC1 gene with AAGG repetition). The clinical picture is protean, associating a neuronopathy, a bilateral vestibulopathy evidenced by an alteration of the oculovestibular reflex (VOR), an atrophy of the cerebellum and a chronic cough.

In the initial stage of the disease the clinical picture is heterogeneous and often incomplete. Ataxia at the beginning of the disease may be the consequence of peripheral nervous system involvement (neuronopathy) and the cerebellar syndrome may manifest itself clinically late.

Eye movement involvement in central nervous system pathologies is common (4). Oculomotor abnormalities are often subclinical and sometimes exclusively identifiable by an instrumental study, video-oculography (VOG) (5).

VOG is a non-invasive examination of eye movements, which is increasingly used in the differential diagnosis of neurodegenerative syndromes (6). This examination allows, among other things, to identify oculomotor anomalies, even discrete and asymptomatic, by studying the combined movements of the eyes and the oculocephalic movements.

The study of oculomotricity by VOG can therefore potentially contribute to the early differential diagnosis of ataxiating neuropathies, including CANVAS, by revealing infra-clinical oculomotor abnormalities correlated with a cerebellar expectation (knowing the role of the dorsal vermis in the precision of saccades and pursuits).


Eligibility criteria: Inclusion Criteria:

Patients followed at the University Hospital of Nîmes between 2018-2021

* Age \> 18 years
* Patients with CANVAS with genetic confirmation (RFC1 gene mutation)
* Patients with axonal neuropathy, autoimmune neuronopathy and anti-MAG neuropathy
* Healthy controls

Primary outcomes:
measure: jerky pursuits
timeFrame: Baseline, Day 0
measure: gaze evoked nystagmus
timeFrame: Baseline, Day 0
measure: down beat nystagmus
timeFrame: Baseline, Day 0
measure: rebound nystagmus
timeFrame: Baseline, Day 0
Secondary outcomes:
Other outcomes:
Locations:
city: Nîmes
country: France
facility: CHU de Nîmes
state: Choisir Une Région
Study officials:
affiliation: Centre Hospitalier Universitaire de Nīmes
name: Anissa MEGZARI
role: STUDY_DIRECTOR
References:
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citation: Weber KP, MacDougall HG, Halmagyi GM, Curthoys IS. Impulsive testing of semicircular-canal function using video-oculography. Ann N Y Acad Sci. 2009 May;1164:486-91. doi: 10.1111/j.1749-6632.2008.03730.x.
citation: Larrazabal AJ, Garcia Cena CE, Martinez CE. Video-oculography eye tracking towards clinical applications: A review. Comput Biol Med. 2019 May;108:57-66. doi: 10.1016/j.compbiomed.2019.03.025. Epub 2019 Mar 30.
citation: Gorges M, Pinkhardt EH, Kassubek J. Alterations of eye movement control in neurodegenerative movement disorders. J Ophthalmol. 2014;2014:658243. doi: 10.1155/2014/658243. Epub 2014 May 18.
citation: Szmulewicz DJ, Waterston JA, MacDougall HG, Mossman S, Chancellor AM, McLean CA, Merchant S, Patrikios P, Halmagyi GM, Storey E. Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS): a review of the clinical features and video-oculographic diagnosis. Ann N Y Acad Sci. 2011 Sep;1233:139-47. doi: 10.1111/j.1749-6632.2011.06158.x.
citation: Cortese A, Reilly MM, Houlden H. RFC1 CANVAS / Spectrum Disorder. 2020 Nov 25. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from http://www.ncbi.nlm.nih.gov/books/NBK564656/
citation: Szmulewicz DJ, Waterston JA, Halmagyi GM, Mossman S, Chancellor AM, McLean CA, Storey E. Sensory neuropathy as part of the cerebellar ataxia neuropathy vestibular areflexia syndrome. Neurology. 2011 May 31;76(22):1903-10. doi: 10.1212/WNL.0b013e31821d746e.