Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Feb 21;11(2):e200253.
doi: 10.1212/NXG.0000000000200253. eCollection 2025 Apr.

Involvement of the Superior Cerebellar Peduncles in GAA- FGF14 Ataxia

Shihan Chen  1 , Catherine Ashton  1   2 , Rawan Sakalla  1 , Guillemette Clement  3 , Sophie Planel  3 , Céline Bonnet  3 , Phillipa J Lamont  2 , Karthik Kulanthaivelu  4 , Atchayaram Nalini  5 , Henry Houlden  6 , Antoine Duquette  7 , Marie-Josée Dicaire  1 , Pablo Iruzubieta Agudo  8 , Javier Ruiz-Martinez  8 , Enrique Marco De Lucas  9 , Rodrigo Sutil Berjon  9 , Jon Infante Ceberio  10 , Elisabetta Indelicato  11 , Sylvia M Boesch  11 , Matthis Synofzik  12   13 , Benjamin Bender  14 , Matt C Danzi  15 , Stephan Zuchner  15 , David Pellerin  1   6 , Bernard Brais  1   16 , Mathilde Renaud  3 , Roberta La Piana  1   16   17
Affiliations

Involvement of the Superior Cerebellar Peduncles in GAA- FGF14 Ataxia

Shihan Chen et al. Neurol Genet. .

Abstract

Objectives: GAA-FGF14 ataxia (SCA27B) is a recently reported late-onset ataxia caused by a GAA repeat expansion in intron 1 of the FGF14 gene. After the clinical observation of superior cerebellar peduncle (SCP) involvement in some affected patients, we sought to verify the prevalence of this finding in our cohort and 4 additional independent cohorts of patients with SCA27B.

Methods: We performed a retrospective review of the brain MRI scans of a total of 87 patients (median age at MRI 69 years; range 28-88 years) from different independent cohorts to assess the presence of SCP involvement, defined as abnormally high T2 signal along the SCP tract.

Results: We observed SCP involvement in 52 patients (52/87; 59.8%) from all the cohorts combined. The finding was replicated at rates ranging from 50% to 62.8% in the cohorts taken separately.

Discussion: SCP involvement in SCA27B is frequent. Its detection may facilitate the diagnostic process of patients with SCA27B.

PubMed Disclaimer

Conflict of interest statement

A. Duquette has received consultancy honoraria from AavantiBio, Novartis, Pfizer Canada, PTC Therapeutics, and Reata Pharmaceuticals, all unrelated to the present manuscript. M. Synofzik has received consultancy honoraria from Ionis, UCB, Prevail, Orphazyme, Servier, Reata, GenOrph, AviadoBio, Biohaven, Zevra, Lilly, and Solaxa, all unrelated to the present manuscript. B. Bender is the cofounder, shareholder and CTO of AIRAmed GmbH. R. La Piana has received speaking honoraria from Novartis unrelated to the present manuscript. Go to Neurology.org/NG for full disclosures.

Figures

Figure 1
Figure 1. Involvement of the Superior Cerebellar Peduncles (SCPs)
Multiplanar FLAIR T2-weighted images of 3 patients showing bilateral and symmetric involvement of the SCP and its decussation within the midbrain. T2 hyperintense signal is visible in the central region of the midbrain in both the axial (A, E, I) and sagittal views (D, H, L), as well as in the coronal plane (C, G, K). The SCPs are involved for their entire length, as shown in the axial views (B, F, J) and in the coronal image (C). The images are from a patient in their 70s with 5 years of disease duration (GAA-TCC expansion size >300) acquired on a 3T MR scanner (A–D), a patient in their 80s with 10 years of disease duration (GAA-TCC expansion size <300) acquired on a 1.5T MR scanner, and a patient in their 70s with 21 years of disease duration (GAA-TCC expansion size >300) acquired on a 1.5T MR scanner (I–L).
Figure 2
Figure 2. SCP Involvement, Longitudinal Study
Axial T2-weighted images in a patient in their 70s with 2 (A) and 4 (B) years of disease duration (GAA-TCC expansion size >300), acquired on a 1.5 (A) and 3T (B) scanner. The SCP involvement is stable over time and can be seen at both a lower and higher magnetic field strength (black arrow).
See this image and copyright information in PMC

References

    1. Pellerin D, Danzi MC, Wilke C, et al. . Deep intronic FGF14 GAA repeat expansion in late-onset cerebellar ataxia. N Engl J Med. 2023;388(2):128-141. doi:10.1056/NEJMoa2207406 - DOI - PMC - PubMed
    1. Rafehi H, Read J, Szmulewicz DJ, et al. . An intronic GAA repeat expansion in FGF14 causes the autosomal-dominant adult-onset ataxia SCA50/ATX-FGF14. Am J Hum Genet. 2023;110(1):105-119. doi:10.1016/j.ajhg.2022.11.015 - DOI - PMC - PubMed
    1. Hengel H, Pellerin D, Wilke C, et al. . As frequent as polyglutamine spinocerebellar ataxias: SCA27B in a large German autosomal dominant ataxia cohort. Mov Disord. 2023;38(8):1557-1558. doi:10.1002/mds.29559 - DOI - PubMed
    1. Wilke C, Pellerin D, Mengel D, et al. . GAA-FGF14 ataxia (SCA27B): phenotypic profile, natural history progression and 4-aminopyridine treatment response. Brain. 2023;146(10):4144-4157. doi:10.1093/brain/awad157 - DOI - PubMed
    1. Bonnet C, Pellerin D, Roth V, et al. . Optimized testing strategy for the diagnosis of GAA-FGF14 ataxia/spinocerebellar ataxia 27B. Sci Rep. 2023;13(1):9737. doi:10.1038/s41598-023-36654-8 - DOI - PMC - PubMed

LinkOut - more resources