Functional and Gait Assessment in Children and Adolescents Affected by Friedreich’s Ataxia: A One-Year Longitudinal Study


Friedreich’s ataxia is the most common autosomal recessive form of neurodegenerative ataxia. We present a longitudinal study on the gait pattern of children and adolescents affected by Friedreich’s ataxia using Gait Analysis and the Scale for the Assessment and Rating of Ataxia (SARA). We assessed the spectrum of changes over 12 months of the gait characteristics and the relationship between clinical and instrumental evaluations. We enrolled 11 genetically confirmed patients affected by Friedreich’s ataxia in this study together with 13 normally developing age-matched subjects. Eight patients completed a 12-month follow-up under the same protocol. By comparing the gait parameters of Friedreich’s ataxia with the control group, we found significant differences for some relevant indexes. In particular, the increased knee and ankle extension in stance revealed a peculiar biomechanical pattern, which correlated reliably with SARA Total, Gait and Sitting scores. The knee pattern showed its consistency also at the follow-up: Knee extension increased from 6.8±3.5° to -0.5±3.7° and was significantly correlated with the SARA total score. This feature anticipated the loss of the locomotor function in two patients. In conclusion, our findings demonstrate that the selective and segmental analysis of kinetic/kinematic features of ataxic gait, in particular the behavior of the knee, provides sensitive measures to detect specific longitudinal and functional alterations, more than the SARA scale, which however has proved to be a reliable and practical assessment tool. Functional outcomes measures integrated by instrumental evaluation increase their sensitivity, reliability and suitability for the follow-up of the disease progression and for the application in clinical trials and in rehabilitative programs.


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Citation: Vasco G, Gazzellini S, Petrarca M, Lispi ML, Pisano A, Zazza M, et al. (2016) Functional and Gait Assessment in Children and Adolescents Affected by Friedreich’s Ataxia: A One-Year Longitudinal Study. PLoS ONE 11(9): e0162463. doi:10.1371/journal.pone.0162463
Editor: Francesc Palau, Sant Joan de Déu Children’s Hospital, SPAIN
Received: March 17, 2016; Accepted: August 23, 2016; Published: September 6, 2016
Copyright: © 2016 Vasco et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting Information files.
Funding: MP reports research funding from the Italian Ministry of Health (Grant number 201501X003626). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.

Friedreich’s ataxia (FRDA) is the most common autosomal recessive form of ataxia that affects approximately 1 in 50,000 Caucasians[1]. FRDA is caused by autosomal recessive GAA trinucleotide expansion in the first intron of the FXN gene on the proximal long arm of chromosome 9, which interferes with frataxin transcription. Moreover 1–3% of the patients are heterozygosus for the GAA expansions on one allele and a point mutation or deletion on the other allele of FXN[2]. Typical age at onset occurs around or even before puberty, although showing a very large variability even between siblings[3]. Progressive gait ataxia, dysmetria, dysdiadocokinesia, muscular weakness, sensory loss, areflexia are typical clinical features of the disease. In addition to neurodegenerative symptoms, there is a multiple systemic involvement that includes cardiomyopathy, scoliosis, diabetes mellitus, foot deformities, abnormalities of eye movements. FRDA patients are wheelchair bound by a disease duration of 15.5 years (range 3–44) with a shortened life expectancy [4,5].

One of the challenges for therapeutic clinical trials in FRDA is the development of outcome measures, which should have good reliability, validity, reproducibility and sensitivity to change. Nowadays, more than in the past, the longitudinal studies of FRDA disease are important to analyze disease progression and to improve the accuracy of prognosis but mostly to prove the adequacy and the sensitivity to change of the outcome measures[6]. An accurate knowledge of the disease natural history is in fact a critical assumption upon which a clinical trial has to be designed.

The Scale for the Assessment and Rating of Ataxia (SARA)[7] for functional assessments has been recognized as the most sensitive scale in a longitudinal analysis of FRDA patients in comparison with ICARS and FARS[6]. SARA has been considered the best choice for its high construct validity, its good effect size and for its compact structure. Sensitivity to longitudinal change of SARA was evaluated in adult FRDA subjects by Marelli and coll.[8] Furthermore, although there are no validated scales for childhood, SARA is reliably applicable to children beyond the age of 10 years and proved to be more suitable for long-term quantitative ataxia assessment from child- to adulthood in comparison to ICARS and BARS[9]. However, the complexity of the neurological phenotype of FRDA due to the intricate interplay between cerebellar degeneration, somatosensory loss and muscle atrophy leads to explore the specific functional and gait changes over time more deeply and with the use of sensitive and objective measures.

Moreover, as well-known in the literature[10–13], the high intra-subject variability of all gait measures is the peculiar and distinctive aspect of ataxic gait that needs an accurate and exhaustive evaluation. However, in FRDA only a few studies have investigated the walking pattern by means of an objective gait analysis. These studies reported a good relationship between gait parameters and the clinical status of disease [12–16].

Unfortunately, these studies have focused only on spatiotemporal parameters (e.g. velocity, step length, single-double support %, etc.) of the gait[13] or in the adult population of FRDA[15]. Other studies compared gait parameters among ataxic patients with the heterogeneous etiology of ataxia[12,17]. Furthermore, only few prospective natural history studies are reported in the literature and all the studies have used simply functional rating scales to describe the progression rate of impairment and disability in FRDA[18–20].

To the best of our knowledge, no longitudinal study on FRDA patients employing gait analysis has been described so far, although this methodology of functional evaluation of gait progression proved to be a useful tool in longitudinal studies both on normal children during growth[21] and on affected children with Cerebral Palsy[22].

In the present longitudinal study, we report changes in a one-year time frame of the gait analysis and SARA in a cohort of children and adolescents affected by FRDA. The goal of this study was threefold: First, to investigate analytically the FRDA gait pattern, through an accurate measurement of kinematic and kinetic data in comparison with healthy controls. Second, to assess the spectrum of changes over 12 months in the individual measures and the correlation between clinical and objective assessment. Third, to identify among the redundant indices of gait analysis which parameters better reflect the core gait pattern of FRDA in terms of sensitivity to change in a longitudinal evaluation and in relation to the functional disease status. Our hypothesis is that functional outcomes measures integrated by instrumental evaluation may increase their sensitivity, reliability and suitability for the follow-up of the disease progression and for the application in clinical trials and in rehabilitative programs.

Materials and Methods

Study Design see