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A quantitative assessment of the evolution of cerebellar syndrome in children with phosphomannomutase-deficiency
Natalia Lourdes Serrano1,2,3, Victor De Diego1,2, Daniel Cuadras4
1Neuropediatric, Radiology and Clinical Biochemistry Departments, Hospital Sant Joan de Déu, Barcelona, Spain.
Insights
Pediatric patients with phosphomannomutase-deficiency (PMM2-CDG) show improved cerebellar function over time, despite cerebellar volume loss. The International Cooperative Ataxia Rating Scale (ICARS) effectively tracks this progression, aiding in the evaluation of future therapies.
Area of Science:
- Neurology
- Genetics
- Pediatrics
Background:
- Phosphomannomutase-deficiency (PMM2-CDG) is a rare genetic disorder.
- Cerebellar syndrome is a key clinical manifestation in PMM2-CDG.
Purpose of the Study:
- To assess the progression of cerebellar syndrome in pediatric PMM2-CDG patients.
- To correlate cerebellar volumetry with clinical status.
- To evaluate the utility of the International Cooperative Ataxia Rating Scale (ICARS) in tracking disease evolution.
Main Methods:
- Prospective evaluation of PMM2-CDG patients aged 5-18 years using ICARS at two time points (≥20 months apart).
- Review of available MRIs and volumetric analysis of the cerebellum.
- Statistical analysis to determine changes in ICARS scores and correlation with cerebellar volume.
Main Results:
- A statistically significant improvement in the overall cerebellar syndrome was observed (ICARS: 35.71 to 30.07, p < 0.001).
- Annual improvement in ICARS scores was 2.64 points (p < 0.001), with significant gains in posture/gait, kinetic functions, and speech.
- A negative correlation was found between ICARS scores and cerebellar volume (r = -0.9, p = 0.037), indicating greater atrophy with higher scores.
Conclusions:
- Pediatric PMM2-CDG patients exhibit stabilization or mild improvement in cerebellar function despite ongoing cerebellar volume loss.
- ICARS is a validated tool for quantifying cerebellar syndrome evolution in PMM2-CDG.
- Sensitive follow-up tools like ICARS are crucial for evaluating potential therapeutic interventions.
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.
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