Clinical Assessment of Dysarthria in Children with Cerebellar Syndrome Associated with PMM2-CDG

Abstract

Phosphomannomutase deficiency (PMM2-CDG) causes a cerebellar syndrome that has been evaluated using the International Cooperative Ataxia Rating Scale (ICARS). However, no particular dysarthria tests have been used. Speech ICARS subscore subjectively assesses fluency and clarity of speech with two items. Repetition of syllables, traditionally used for characterization of ataxic speech, was validated in early-onset ataxia conditions. We assess the validity of the PATA test (SCA Functional Index [SCAFI]) in PMM2-CDG patients.

PATA rates from 20 patients were compared with a control population were and correlated with ICARS and neuroimaging.

There was a difference between the PATA rate in patients and controls. PATA rate increased with age in controls. In patients, the improvement of PATA rate with age was not significant. In patients, the PATA rate was negatively correlated with the total ICARS score and the Speech ICARS subscore. Regarding neuroimaging, midsaggital vermis relative diameter was positively correlated with PATA results. These last differences were also significant when the results are corrected by age.

PATA rate provides an easy measure for a quantitative assessment of dysarthria that may help clinicians to monitor patients' evolution in a regular consultation. It could also be used in PMM2-CDG clinical trials implementing ICARS speech subscore information.

Keywords

cerebellar syndrome - congenital disorders of glycosylation - dysarthria - magnetic resonance imaging - PMM2-CDG

• References

• 1 Freeze HH, Eklund EA, Ng BG, Patterson MC. Neurology of inherited glycosylation disorders. Lancet Neurol 2012; 11 (05) 453-466
• 2 Pérez-Dueñas B, García-Cazorla A, Pineda M. , et al. Long-term evolution of eight Spanish patients with CDG type Ia: typical and atypical manifestations. Eur J Paediatr Neurol 2009; 13 (05) 444-451
• 3 Barone R, Carrozzi M, Parini R. , et al. A nationwide survey of PMM2-CDG in Italy: high frequency of a mild neurological variant associated with the L32R mutation. J Neurol 2015; 262 (01) 154-164
• 4 Trouillas P, Takayanagi T, Hallett M. , et al; The Ataxia Neuropharmacology Committee of the World Federation of Neurology. International Cooperative Ataxia Rating Scale for pharmacological assessment of the cerebellar syndrome. J Neurol Sci 1997; 145 (02) 205-211
• 5 Serrano M, de Diego V, Muchart J. , et al. Phosphomannomutase deficiency (PMM2-CDG): ataxia and cerebellar assessment. Orphanet J Rare Dis 2015; 10: 138
• 6 Serrano NL, De Diego V, Cuadras D. , et al; CDG Spanish-Consortium. A quantitative assessment of the evolution of cerebellar syndrome in children with phosphomannomutase-deficiency (PMM2-CDG). Orphanet J Rare Dis 2017; 12 (01) 155
• 7 Schmitz-Hübsch T, du Montcel ST, Baliko L. , et al. Scale for the assessment and rating of ataxia: development of a new clinical scale. Neurology 2006; 66 (11) 1717-1720
• 8 Schmahmann JD, Gardner R, MacMore J, Vangel MG. Development of a brief ataxia rating scale (BARS) based on a modified form of the ICARS. Mov Disord 2009; 24 (12) 1820-1828
• 9 Schmitz-Hübsch T, Giunti P, Stephenson DA. , et al. SCA Functional Index: a useful compound performance measure for spinocerebellar ataxia. Neurology 2008; 71 (07) 486-492
• 10 Kuiper MJ, Brandsma R, Lawerman TF. , et al. Assessment of speech in early-onset ataxia: a pilot study. Dev Med Child Neurol 2014; 56 (12) 1202-1206
• 11 Achouitar S, Mohamed M, Gardeitchik T. , et al. Nijmegen paediatric CDG rating scale: a novel tool to assess disease progression. J Inherit Metab Dis 2011; 34 (04) 923-927
• 12 de Diego V, Martínez-Monseny AF, Muchart J. , et al; Collaborators of the CDG Spanish-Consortium. Longitudinal volumetric and 2D assessment of cerebellar atrophy in a large cohort of children with phosphomannomutase deficiency (PMM2-CDG). J Inherit Metab Dis 2017; 40 (05) 709-713
• 13 Pérez-Cerdá C, Girós ML, Serrano M. , et al. A population-based study on congenital disorders of protein N- and combined with O-glycosylation experience in clinical and genetic diagnosis. J Pediatr 2017; 183: 170-177.e1
• 14 Knuijt S, Kalf JG, van Engelen BGM, de Swart BJM, Geurts ACH. The Radboud dysarthria assessment: development and clinimetric evaluation. Folia Phoniatr Logop 2017; 69 (04) 143-153
• 15 Al-Maawali A, Blaser S, Yoon G. Diagnostic approach to childhood-onset cerebellar atrophy: a 10-year retrospective study of 300 patients. J Child Neurol 2012; 27 (09) 1121-1132