TY - JOUR
T1 - Clinical and radiological correlates of activities of daily living in cerebellar atrophy caused by PMM2 mutations (PMM2-CDG)
AU - Pettinato, Fabio
AU - Mostile, Giovanni
AU - Battini, Roberta
AU - Martinelli, Diego
AU - Madeo, Annalisa
AU - Biamino, Elisa
AU - Frattini, Daniele
AU - Garozzo, Domenico
AU - Gasperini, Serena
AU - Parini, Rossella
AU - Sirchia, Fabio
AU - Sortino, Giuseppe
AU - Sturiale, Luisa
AU - Matthijs, Gert
AU - Morrone, Amelia
AU - Di Rocco, Maja
AU - Rizzo, Renata
AU - Jaeken, Jaak
AU - Fiumara, Agata
AU - Barone, Rita
N1 - Funding Information:
Open access funding provided by Università degli Studi di Catania within the CRUI-CARE Agreement. The study was partially funded by a grant from CDG-Italy and CDG-Swiss family associations. Funding organizations had no role in the design or conduct of this research.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/8
Y1 - 2021/8
N2 - We aimed to identify clinical, molecular and radiological correlates of activities of daily living (ADL) in patients with cerebellar atrophy caused by PMM2 mutations (PMM2-CDG), the most frequent congenital disorder of glycosylation. Twenty-six PMM2-CDG patients (12 males; mean age 13 ± 11.1 years) underwent a standardized assessment to measure ADL, ataxia (brief ataxia rating scale, BARS) and phenotype severity (Nijmegen CDG rating scale, NCRS). MRI biometry of the cerebellum and the brainstem were performed in 23 patients (11 males; aged 5 months–18 years) and 19 control subjects with equal gender and age distributions. The average total ADL score was 15.3 ± 8.5 (range 3–32 out of 36 indicating severe functional disability), representing variable functional outcome in PMM2-CDG patients. Total ADL scores were significantly correlated with NCRS (r2 = 0.55, p < 0.001) and BARS scores (r2 = 0.764; p < 0.001). Severe intellectual disability, peripheral neuropathy, and severe PMM2 variants were all significantly associated with worse functional outcome. Higher ADL scores were significantly associated with decreased diameters of cerebellar vermis (r2 = 0.347; p = 0.004), hemispheres (r2 = 0.436; p = 0.005), and brainstem, particularly the mid-pons (r2 = 0.64; p < 0.001) representing the major radiological predictor of functional disability score in multivariate regression analysis. We show that cerebellar syndrome severity, cognitive level, peripheral neuropathy, and genotype correlate with ADL used to quantify disease-related deficits in PMM2-CDG. Brainstem involvement should be regarded among functional outcome predictors in patients with cerebellar atrophy caused by PMM2-CDG.
AB - We aimed to identify clinical, molecular and radiological correlates of activities of daily living (ADL) in patients with cerebellar atrophy caused by PMM2 mutations (PMM2-CDG), the most frequent congenital disorder of glycosylation. Twenty-six PMM2-CDG patients (12 males; mean age 13 ± 11.1 years) underwent a standardized assessment to measure ADL, ataxia (brief ataxia rating scale, BARS) and phenotype severity (Nijmegen CDG rating scale, NCRS). MRI biometry of the cerebellum and the brainstem were performed in 23 patients (11 males; aged 5 months–18 years) and 19 control subjects with equal gender and age distributions. The average total ADL score was 15.3 ± 8.5 (range 3–32 out of 36 indicating severe functional disability), representing variable functional outcome in PMM2-CDG patients. Total ADL scores were significantly correlated with NCRS (r2 = 0.55, p < 0.001) and BARS scores (r2 = 0.764; p < 0.001). Severe intellectual disability, peripheral neuropathy, and severe PMM2 variants were all significantly associated with worse functional outcome. Higher ADL scores were significantly associated with decreased diameters of cerebellar vermis (r2 = 0.347; p = 0.004), hemispheres (r2 = 0.436; p = 0.005), and brainstem, particularly the mid-pons (r2 = 0.64; p < 0.001) representing the major radiological predictor of functional disability score in multivariate regression analysis. We show that cerebellar syndrome severity, cognitive level, peripheral neuropathy, and genotype correlate with ADL used to quantify disease-related deficits in PMM2-CDG. Brainstem involvement should be regarded among functional outcome predictors in patients with cerebellar atrophy caused by PMM2-CDG.
KW - Activities of daily living
KW - Ataxia
KW - Cerebellar atrophy
KW - Congenital disorder(s) of glycosylation
KW - PMM2 variants
KW - Pons atrophy
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U2 - 10.1007/s12311-021-01242-x
DO - 10.1007/s12311-021-01242-x
M3 - Article
C2 - 33619652
AN - SCOPUS:85101683015
VL - 20
SP - 596
EP - 605
JO - Cerebellum
JF - Cerebellum
SN - 1473-4222
IS - 4
ER -