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. 2024 Nov 1;10(6):e200208.
doi: 10.1212/NXG.0000000000200208. eCollection 2024 Dec.

Bilateral Dentate Nuclei Hyperintensities and Response to 4-Aminopyridine in a Patient With Childhood-Onset GAA- FGF14-Related Ataxia

Pierfrancesco Mitrotti  1 , Elisa Vegezzi  1 , Roberta Zangaglia  1 , Ilaria Palmieri  1 , Marie-Josée Dicaire  1 , Simone Gana  1 , Sayna Rahimi Aghdas  1 , Silvia Nicolosi  1 , Anna Pichiecchio  1 , Cristina Tassorelli  1 , Enza Maria Valente  1 , Micol Avenali  1
Affiliations

Bilateral Dentate Nuclei Hyperintensities and Response to 4-Aminopyridine in a Patient With Childhood-Onset GAA- FGF14-Related Ataxia

Pierfrancesco Mitrotti et al. Neurol Genet. .

Abstract

Objectives: To report a novel imaging finding of bilateral dentate nuclei hyperintensities in a case of childhood-onset GAA-FGF14-related ataxia (spinocerebellar ataxia 27B, SCA27B) and response to 4-aminopyridine (4-AP).

Methods: A 53-year-old woman with unsolved progressive cerebellar ataxia of childhood onset underwent clinical and imaging assessment and extensive genetic investigation.

Results: After excluding Friedreich ataxia, most common spinocerebellar ataxia-related expansions, and pathogenic variants in ataxia-related genes through exome sequencing, targeted long-range PCR and repeat-primed PCR analysis revealed a heterozygous pathogenic (GAA)302 expansion in FGF14. Brain MRI showed bilateral dentate nuclei hyperintensities and peridentate white matter degeneration, a feature never reported before in SCA27B. Gait ataxia and frequency of falls improved after starting 4-AP.

Discussion: We confirm that SCA27B, initially considered a late-onset condition, can present with very early onset in childhood and describe a novel imaging feature of this common hereditary ataxia. Previous imaging studies had described a spectrum of findings, variably including cerebellar vermian and hemispheric atrophy, hyperintensities of the superior cerebellar peduncles, cerebral and brainstem atrophy, ventricular enlargement, and corpus callosum thinning. In this case, T2/FLAIR bilateral dentate nuclei hyperintensities and peridentate white matter degeneration expand the neuroradiologic spectrum associated with GAA-FGF14-related ataxia of long duration.

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Conflict of interest statement

M. Avenali is supported by Ministry of University and Research (MUR), National Recovery 231 and Resilience Plan (NRRP), project MNESYS (PE0000006). E.M. Valente is the Associate Editor of Journal of Medical Genetics, Genetics Section Editor of Pediatric Research, Genetics Section Editor of The Cerebellum, Genetics Section Editor of Neurological Sciences, a member of the Editorial Board of Movement Disorders Clinical Practice, and a member of the Steering Committee of ASAP GP2 (Global Parkinson Genetic Program) and has received research support from the Italian Ministry of Health, CARIPLO Foundation, Telethon, Foundation Italy, Pierfranco and Luisa Mariani Foun-dation, and European Community (Eranet Neuron). Go to Neurology.org/NG for full disclosures.

Figures

Figure
Figure. Brain MRI of the Patient
Axial T2 FLAIR-weighted MR image demonstrates bilateral abnormal high signal intensity in the hilum of dentate nuclei and peridentate white matter (A, white arrow indicating dentate nuclei hyperintensity). The section also shows an enlargement of the fourth ventricle and a mild downsizing of the middle cerebellar peduncles. Coronal sections (B and C) show atrophy of both cerebellar hemispheres and superior cerebellar peduncles. Parasagittal (D) and mid-sagittal (E) 3D GRE T1-weighted MR sections demonstrate marked atrophy of the vermis, particularly its superior portion and cerebellar hemispheres. Parasagittal 3D T1-weighted MR image (D) shows also mild bilateral enlargement of parietal sulci.
See this image and copyright information in PMC

References

    1. Shakkottai VG, Xiao M, Xu L, et al. . FGF14 regulates the intrinsic excitability of cerebellar Purkinje neurons. Neurobiol Dis. 2009;33(1):81-88. doi:10.1016/j.nbd.2008.09.019 - DOI - PMC - PubMed
    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(21):128-141. doi:10.1056/NEJMoa2207406 - DOI - PMC - PubMed
    1. Sakalla R, Chen S, Pellerin D, et al. . Neuroradiological findings in GAA-FGF14 ataxia: qualitative retrospective review and volumetric analysis in a series of 26 subjects. J Neurol Sci. 2023;455:121187. doi:10.1016/j.jns.2023.121187 - DOI
    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. Méreaux JL, Davoine CS, Pellerin D, et al. . Clinical and genetic keys to cerebellar ataxia due to FGF14 GAA expansions. EBioMedicine. 2024;99:104931. doi:10.1016/j.ebiom.2023.104931 - DOI - PMC - PubMed

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