TY - JOUR
T1 - A quantitative assessment of the evolution of cerebellar syndrome in children with phosphomannomutase-deficiency (PMM2-CDG)
AU - Serrano, Natalia Lourdes
AU - De Diego, Victor
AU - Cuadras, Daniel
AU - Martinez Monseny, Antonio F.
AU - Velázquez-Fragua, Ramón
AU - López, Laura
AU - Felipe, Ana
AU - Gutiérrez-Solana, Luis G.
AU - Macaya, Alfons
AU - Serrano, Mercedes
AU - Miranda, Ma Concepción
AU - Carratala, Francisco
AU - Póo, M. Pilar
AU - Robles, Bernabé
AU - Couce, María L.
AU - Girós, Marisa
AU - Gort, Laura
AU - Montero, Raquel
AU - Artuch, Rafael
AU - Pérez-Cerdá, Celia
AU - Muchart, Jordi
PY - 2017/9/15
Y1 - 2017/9/15
N2 - © 2017 The Author(s). Background: We aim to delineate the progression of cerebellar syndrome in children with phosphomannomutase-deficiency (PMM2-CDG) using the International Cooperative Ataxia Rating Scale (ICARS). We sought correlation between cerebellar volumetry and clinical situation. We prospectively evaluated PMM2-CDG patients aged from 5 to 18 years through ICARS at two different time points set apart by at least 20 months. We reviewed available MRIs and performed volumetric analysis when it was possible. Results: From the eligible 24, four patients were excluded due to severe mental disability (n = 2) and supratentorial lesions (n = 2). Two different ICARS evaluations separated by more than 20 months were available for 14 patients showing an improvement in the cerebellar syndrome: ICARS1: 35.71 versus ICARS2: 30.07 (p < 0.001). When we considered time, we saw an improvement of 2.64 points in the ICARS per year with an SD of 1.97 points (p < 0.001). The ICARS subscales results improved with time, reaching statistical significance in "Posture and gait" (p < 0.001), "Kinetic functions" (p = 0.04) and "Speech abnormalities" (p = 0.045). We found a negative correlation between the ICARS results and total cerebellar volume (r = -0.9, p = 0.037) in a group of five patients with available volumetric study, meaning that the higher the ICARS score, the more severe was the cerebellar atrophy. Conclusions: Our study shows a stabilization or mild improvement in the cerebellar functions of paediatric PMM2-CDG patients despite cerebellar volume loss. ICARS is a valid scale to quantify the evolution of cerebellar syndrome in PMM2-CDG patients. The availability of ICARS and other reliable and sensitive follow-up tools may prove essential for the evaluation of potential therapies.
AB - © 2017 The Author(s). Background: We aim to delineate the progression of cerebellar syndrome in children with phosphomannomutase-deficiency (PMM2-CDG) using the International Cooperative Ataxia Rating Scale (ICARS). We sought correlation between cerebellar volumetry and clinical situation. We prospectively evaluated PMM2-CDG patients aged from 5 to 18 years through ICARS at two different time points set apart by at least 20 months. We reviewed available MRIs and performed volumetric analysis when it was possible. Results: From the eligible 24, four patients were excluded due to severe mental disability (n = 2) and supratentorial lesions (n = 2). Two different ICARS evaluations separated by more than 20 months were available for 14 patients showing an improvement in the cerebellar syndrome: ICARS1: 35.71 versus ICARS2: 30.07 (p < 0.001). When we considered time, we saw an improvement of 2.64 points in the ICARS per year with an SD of 1.97 points (p < 0.001). The ICARS subscales results improved with time, reaching statistical significance in "Posture and gait" (p < 0.001), "Kinetic functions" (p = 0.04) and "Speech abnormalities" (p = 0.045). We found a negative correlation between the ICARS results and total cerebellar volume (r = -0.9, p = 0.037) in a group of five patients with available volumetric study, meaning that the higher the ICARS score, the more severe was the cerebellar atrophy. Conclusions: Our study shows a stabilization or mild improvement in the cerebellar functions of paediatric PMM2-CDG patients despite cerebellar volume loss. ICARS is a valid scale to quantify the evolution of cerebellar syndrome in PMM2-CDG patients. The availability of ICARS and other reliable and sensitive follow-up tools may prove essential for the evaluation of potential therapies.
KW - Cerebellum
KW - Congenital disorders of glycosylation
KW - Developmental disorders
KW - Gait disorders/ataxia
KW - ICARS
KW - MRI
U2 - 10.1186/s13023-017-0707-0
DO - 10.1186/s13023-017-0707-0
M3 - Article
SN - 1750-1172
VL - 12
JO - Orphanet Journal of Rare Diseases
JF - Orphanet Journal of Rare Diseases
IS - 1
M1 - 155
ER -