Reliability of phenotypic early‐onset ataxia assessment: a pilot study

Abstract

AIM To investigate the interobserver agreement on phenotypic early-onset ataxia (EOA) assessment and to explore whether the Scale for Assessment and Rating of Ataxia (SARA) could provide a supportive marker.METHOD Seven movement disorder specialists provided independent phenotypic assessments of potentially ataxic motor behaviour in 40 patients (mean age 15y [range 5-34]; data derived from University Medical Center Groningen medical records 1998-2012). We determined interobserver agreement by Fleiss' kappa. Furthermore, we compared percentage SARA subscores ([subscore/total score]9100%) between 'indisputable' (primary ataxia recognition by at least six observers) and 'mixed' (ataxia recognition, unfulfilling 'indisputable' criteria) EOA phenotypes.RESULTS Agreement on phenotypic EOA assessment was statistically significant (p<0.001), but of moderate strength (Fleiss' kappa=0.45; 95% CI 0.38-0.51). During mild disease progression, percentage SARA gait subscores discriminated between 'indisputable' and 'mixed' EOA phenotypes. In patients with percentage SARA gait subscores >30%, primary ataxia was more frequently present than in those with subscores <30% (p=0.001).INTERPRETATION Among movement-disorder professionals from different disciplines, interobserver agreement on phenotypic EOA recognition is of limited strength. SARA gait subscores can provide a supportive discriminative marker between EOA phenotypes. Hopefully, future phenotypic insight will contribute to the inclusion of uniform, high-quality data in international EOA databases.Ataxia is described by an impairment of the smooth performance of goal-directed movements, 1 resulting in impaired 'unconscious' decision making about balance, speed, force, and direction of intended movements. [2][3][4] Intentional motor behaviour may thus be affected by ataxic limb movements (intention and action tremor, dysdiadochokinesis, rebound, hypermetria), trunk movements (with staggering, swaying, and titubation), eye movements (nystagmus, saccades, overand undershoot), and speech (dysarthria, dysrhythmia). The underlying neuropathology involves abnormal spinal afferent input and/or cerebellar dysfunction, hampering multisensory fine-tuning and timing of motor output. In the literature, the concept of 'early-onset ataxia' (EOA) is used to define the initiation of ataxia before the 25th year of life. 5,6 The estimated EOA prevalence is about 14.6 per 100 000.7 As implicated by the large range in the age at onset, there is an enormous variety in underlying (genetic and metabolic) disorders. In this perspective, international EOA databases aim to (1) provide insight in the longitudinal disease course, (2) identify new genes, (3) design new treatment strategies, and (4) characterize uniform and transparent markers for disease monitoring. In the absence of a criterion standard, EOA patient inclusion will depend on subjective phenotypic recognition of ataxia. This process is complex for several reasons. In young children, it is wellknown that the physiological maturation of th...

Paediatric motor phenotypes in early‐onset ataxia, developmental coordination disorder, and central hypotonia

“…When considering the incomplete phenotypic separation between EOA and DCD phenotypes, we explored the effect of previously proven, standardized phenotypic EOA features on phenotypic homogeneity. One validated standardized phenotypic EOA feature is that patients with EOA are likely to reveal assembled SARA motor (sub)scores from different SARA domains, reflecting global cerebellar involvement . In patients with EOA, this feature is understandable by the exclusion of acquired cerebellar lesions from the group.…”

“…3,4 In general, lack of muscle tone can be associated with kinetic inaccuracy (sloppiness) and balance problems, which may mimic cerebellar dysfunction. 16,17 In the absence of criterion standards 18 and in the context of ambiguous clinical descriptions, an insight into the reliability of phenotypic differentiation between EOA and other disorders with impaired coordination (DCD and central hypotonia) is important. In the present study, we aimed to: (1) investigate interobserver agreement on phenotypic assessment of EOA, DCD, and central hypotonia; (2) compare Scale for Assessment and Rating of Ataxia (SARA) 19 and Paediatric Balance Scale (PBS) 20 scores between phenotypic assignments; and (3) explore the effect of three scientifically validated, standardized EOA features on phenotypic consensus.…”

Reliability and discriminant validity of ataxia rating scales in early onset ataxia

“…According to Cicchetti, official cut‐offs for qualitative rating of ICC values are as follows: ICC <0.40, poor; 0.40 to 0.59, fair; 0.60 to 0.74, good; 0.75 to 1.00, excellent. For uniformity reasons with previously published data, we also interpreted outcomes by Landis & Koch criteria, which are originally described for categorical data. According to Landis & Koch, we characterized ICC outcomes by: ICC <0.20, slight; 0.21 to 0.40, fair; 0.41 to 0.60, moderate; 0.61 to 0.80, substantial; >0.81, almost perfect.…”

“…EOA with other movement disorder features that may prevail over ataxia) . Especially in children, EOA is often prevalent as a combined phenotype, with concurrent features of dystonia, myoclonus, chorea, and spasticity, which may prevail over ataxia . This heterogeneity makes uniform phenotypic EOA assessment a challenging task for paediatric movement disorder specialists.…”

“…This heterogeneity makes uniform phenotypic EOA assessment a challenging task for paediatric movement disorder specialists. Therefore, quantitative ataxia rating scales (ARS) are often used as additionally reproducible ‘surrogate’ biomarkers for ataxia …”