Dataset Information

Neuroradiological findings in GAA-FGF14 ataxia (SCA27B): more than cerebellar atrophy.

ABSTRACT:

Background and objectives

GAA-FGF14 ataxia (SCA27B) is a recently reported late-onset cerebellar ataxia (LOCA) caused by a GAA repeat expansion in intron 1 of the FGF14 gene. Initial studies reviewing MR images of GAA-FGF14 ataxia patients revealed variable degree of cerebellar atrophy in 74-97% of them. A more detailed brain imaging characterization of GAA-FGF14 ataxia is now needed to provide 1) supportive diagnostic features and earlier disease recognition and 2) further information about the pathophysiology of the disease.

Methods

We reviewed the brain MRIs of 35 patients (median age at MRI 63 years; range 28-88 years; 16 females) from Quebec (n=27), Nancy (n=3), Perth (n=3) and Bengaluru (n=2) including longitudinal studies for 7 subjects. We performed qualitative analyses to assess the presence and degree of atrophy in vermis, cerebellar hemispheres, brainstem, cerebral hemispheres, and corpus callosum, as well as white matter involvement. Following the identification of the superior cerebellar peduncles involvement, we verified its presence in 54 GAA-FGF14 ataxia patients from four independent cohorts (Tübingen n=29; Donostia n=12; Innsbruck n=7; Cantabria n=6). To assess lobular atrophy, we also performed quantitative cerebellar segmentation in 5 subjects and 5 age-matched controls.

Results

Cerebellar atrophy of variable degree was documented in 33 subjects (94.3%); limited to the vermis in 11 subjects, extended to the hemispheres in 22. We observed bilateral involvement of the superior cerebellar peduncles (SCPs) in 22 subjects (62.8%). We confirmed this finding in 30/54 (55.6%) GAA-FGF14 positive subjects from the validation cohorts. Additional findings were: cerebral atrophy in 15 subjects (42.9%), ventricular enlargement in 13 (37.1%), corpus callosum thinning in 7 (20%), and brainstem atrophy in 1 (2.8%). Cerebellar segmentation showed reduced volumes of lobules X and IV in affected individuals.

Discussion

Our study confirms that cerebellar atrophy is a key feature of GAA-FGF14 ataxia. The frequent SCP involvement observed in different cohorts may be specific to GAA-FGF14 ataxia, and its detection can support and accelerate the diagnosis. The predominant involvement of vestibulocerebellar lobule X correlates with the finding of downbeat nystagmus frequently observed in GAA-FGF14 ataxia patients.

SUBMITTER: Chen S

PROVIDER: S-EPMC10889027 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Neuroradiological findings in GAA-<i>FGF14</i> ataxia (SCA27B): more than cerebellar atrophy.

Chen Shihan S Ashton Catherine C Sakalla Rawan R Clement Guillemette G Planel Sophie S Bonnet Céline C Lamont Phillipa P Kulanthaivelu Karthik K Nalini Atchayaram A Houlden Henry H Duquette Antoine A Dicaire Marie-Josée MJ Agudo Pablo Iruzubieta PI Martinez Javier Ruiz JR de Lucas Enrique Marco EM Berjon Rodrigo Sutil RS Ceberio Jon Infante JI Indelicato Elisabetta E Boesch Sylvia S Synofzik Matthis M Bender Benjamin B Danzi Matt C MC Zuchner Stephan S Pellerin David D Brais Bernard B Renaud Mathilde M La Piana Roberta R

medRxiv : the preprint server for health sciences 20240516

<h4>Background</h4>GAA-<i>FGF14</i> ataxia (SCA27B) is a recently reported late-onset ataxia caused by a GAA repeat expansion in intron 1 of the <i>FGF14</i> gene. Initial studies revealed cerebellar atrophy in 74-97% of patients. A more detailed brain imaging characterization of GAA-<i>FGF14</i> ataxia is now needed to provide supportive diagnostic features and earlier disease recognition.<h4>Methods</h4>We performed a retrospective review of the brain MRIs of 35 patients (median age at MRI 63 ...[more]

PMID: 38405699

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