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@ARTICLE{Petit:280789,
author = {Petit, Emilien and López Domínguez, Daniel and Marelli,
Cecilia and Sayah, Sabrina and Pulst, Stefan M and Faber,
Jennifer and Oz, Gulin and Paulson, Henry L and Ashizawa,
Tetsuo and Tezenas du Montcel, Sophie and Durr, Alexandra
and Coarelli, Giulia},
collaboration = {Consortium, READISCA},
title = {{P}revalence, {S}everity, and {P}rogression of {C}erebellar
{C}ognitive-{A}ffective {S}yndrome in {P}atients {W}ith
{S}pinocerebellar {A}taxias.},
journal = {Neurology},
volume = {105},
number = {5},
issn = {0028-3878},
address = {Philadelphia, Pa.},
publisher = {Wolters Kluwer},
reportid = {DZNE-2025-00973},
pages = {e213980},
year = {2025},
abstract = {Cerebellar cognitive-affective syndrome (CCAS) results from
cerebellar degeneration, but its prevalence in
spinocerebellar ataxias (SCAs) remains underexplored. This
study assessed CCAS prevalence, severity, and progression
across different SCAs.We included polyglutamine (PolyQ) SCA
expansion carriers (ATXN1/SCA1, ATXN2/SCA2, ATXN3/SCA3, and
ATXN7/SCA7), patients with FGF14/SCA27B and SPG7, and
controls. Cognitive function was assessed with the CCAS
scale and ataxia severity with the Scale for the Assessment
and Rating of Ataxia (SARA) and Composite Cerebellar
Functional Severity (CCFS) score. We correlated CCAS score
with ataxia severity, brain MRI, and plasma neurofilament
light chain (NfL) levels. Subtest comparisons among
genotypes were adjusted for age, education, and SARA score.
In PolyQ SCA carriers, we explored CCAS progression.We
included 371 participants: 66 with SCA1, 28 with SCA2, 158
with SCA3, 24 with SCA7, 35 with SPG7, 17 with SCA27B, and
43 controls. Those with SCA27B and SPG7 were older (69.5 ±
9.5 and 57.8 ± 10.6 years) with lower education (11.4 ±
4.2 and 12.7 ± 3.6 years) than those with PolyQ SCAs (from
40.3 ± 14.0 for SCA7 group to 45.9 ± 11.2 years in SCA3
group, p < 0.0001; education ranging from 14.4 ± 3.1 for
SCA2 group to 15.4 ± 2.8 years for SCA7 group, p < 0.0001).
Among ataxic patients, definite CCAS was detected in $88\%$
of patients with SCA27B and $71\%$ of SPG7 carriers,
followed by SCA2 $(67\%),$ SCA7 $(67\%),$ SCA1 $(50\%),$ and
SCA3 $(41\%)$ groups. Among preataxic PolyQ SCA carriers,
CCAS was present in $11\%$ (10/89), similar to controls
$(11.6\%,$ p = 1). However, phonemic fluency showed an early
impairment in preataxic SCA1 carriers (11.8 ± 4.5 vs 14.6
± 3.8, p = 0.04). In PolyQ SCA carriers, the CCAS total raw
score correlated with SARA score (r = -0.54, p < 0.0001),
CCFS score (r = -0.45; p < 0.0001), and plasma NfL levels (r
= -0.26, p = 0.002). CCAS scores correlated with cerebellar
volume in those with SCA2 (r = 0.64, p < 0.001). Patients
with SPG7 showed significantly poorer performance in
executive function, short-term memory, and abstract
reasoning compared with those with SCA3 and SCA7. In PolyQ
SCA carriers, improvements were observed during the first 3
years after inclusion (+2.0 ± 0.7 points, p = 0.002; +2.6
± 0.8 points, p = 0.0007; +2.7 ± 0.8, p = 0.001,
respectively). By year 4, the increase was not significant
(+0.73 ± 1.16 points, p = 0.52).We observed early cognitive
impairment in PolyQ SCA carriers, correlating with clinical
measures, NfL levels, and cerebellum volume. Improvement
over 3 years likely reflects a practice effect, potentially
limiting the scale's longitudinal utility.},
keywords = {Humans / Spinocerebellar Ataxias: genetics /
Spinocerebellar Ataxias: epidemiology / Spinocerebellar
Ataxias: complications / Spinocerebellar Ataxias: diagnostic
imaging / Male / Female / Middle Aged / Disease Progression
/ Adult / Prevalence / Severity of Illness Index / Aged /
Magnetic Resonance Imaging / Neurofilament Proteins: blood /
Peptides: genetics / Cerebellar Diseases: epidemiology /
neurofilament protein L (NLM Chemicals) / Neurofilament
Proteins (NLM Chemicals) / Peptides (NLM Chemicals)},
cin = {Clinical Research (Bonn)},
ddc = {610},
cid = {I:(DE-2719)1011001},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40834346},
pmc = {pmc:PMC12367419},
doi = {10.1212/WNL.0000000000213980},
url = {https://pub.dzne.de/record/280789},
}