The International Cooperative Ataxia Rating Scale shows strong age‐dependency in children

SIR–Many metabolic and neurodegenerative disorders in children are associated with relentlessly progressive ataxia. In order to attenuate disease progression, treatment strategies can involve the prescription of orphan drugs. When such innovative treatment strategies are applied in small, non-placebo-controlled pediatric patient groups, standardized, longitudinal, patient-based evaluations are frequently involved. Both in children and adults, the International Cooperative Ataxia Rating Scale (ICARS) is a commonly used evaluation, initially designed for longitudinal assessment of pharmacological therapies in patients with cerebellar ataxia.1-3 The ICARS is composed of four clinical sub-scores involving the following specific aspects: posture and gait, limb coordination, speech, and oculomotor function.4 The total sum of these sub-scores, the ICARS score, ranges from the optimal outcome ‘0’ to the most severely affected outcome ‘100’. In children, the ICARS score has been applied for the evaluation of medication, such as in patients with Friedreich’s ataxia or vitamin E deficiency5-8 and for the investigation of the relationship between cerebellar structure and function.9-11 Until now, however, most of these trials compare their ICARS scores in children with adults instead of paediatric reference values.5-8, 10 In young children, this may induce the risk that age-dependent achievement of fine motor skills, coordination, concentration, and muscle force influences the interpretation of ICARS outcome without interference of disease state, course, or therapy. Interestingly, the potential age-dependency of the ICARS score has not been addressed thus far. To investigate the presence of age-dependency, we scored ICARS in 20 healthy children in a cross-sectional way. All the children (four males, 16 females; aged 4–14y) were born after an uneventful pregnancy at term and had developed without adverse events or cognitive deficits. All children were of Caucasian origin, and from families of middle-class socio-economic status. The study was approved by the local medical ethics committee of the University Medical Center, Groningen, the Netherlands. Informed consent was obtained from the parents. Cross-sectional assessment in the included children showed that the ICARS score decreased from 13 at 4 years of age to the ‘adult’ optimum of ‘0’ at about 13 years of age (Fig. 1; r=0.85; polynominal regression). Cross-sectional International Cooperative Ataxia Rating Scale (ICARS) scores versus age in 20 healthy control children. ICARS scores decreased with age until the optimum (‘0’) was reached at about 13 years of age. r=−0.85 (polynomial regression). Present data in healthy children show that ICARS scores improve with age, in a non-linear fashion. These age-dependent findings are in accordance with other neurodevelopmental studies (using the Zürich Neuromotor Assessment), indicating that parameters for complex neuromotor behavior continue to improve during childhood until puberty.12, 13 Timed performances of alternating and sequential movements were shown to reach their optimum late (i.e. at 18y).12 Regarding associated movements coinciding with complex movements (involving diadochokinesis, alternating and sequential movements), females were shown to mature earlier than males.13 From the present findings in healthy, predominantly female children, we conclude that ICARS scores improve during normal development, at least until 13 years of age. Our findings may have direct implications for the application of ICARS scores in young children. Comparison with adult rather than with paediatric ICARS reference values could lead to misinterpretation of longitudinal outcomes. In particular, ‘improved’ paediatric ICARS scores could be mistakenly held for a therapeutic effect, rather than for an age-dependent (maturation-related) effect. To allow accurate interpretation of longitudinal ICARS scores in children with ataxia, detailed age-specific paediatric reference values and/or carefully designed control studies are needed.