Charcot-Marie-Tooth 1A patients with low level of impairment have a higher energy cost of walking than healthy individuals

Abstract

The study aimed at quantifying the walking energy cost of a group of Charcot-Marie-Tooth 1A patients (CMT1A), with low severity of walking impairment, in comparison with healthy individuals. Oxygen uptake was measured in 8 patients (age-range 20–48 years; Barthel >90; Tinetti >20) and 8 healthy individuals, matched for age and gender, when walking on a circuit for 5-min at their self-selected speeds (“slow”, “comfortable” and “fast”). Both comfortable and fast speeds were lower in patients than in the control group (0.92 ± 0.16 vs 1.16 ± 0.22 and 1.27 ± 0.27 vs 1.61 ± 0.22 m s⁻¹, respectively; P < 0.05), whereas walking energy cost per unit of distance was higher in patients than in the control group (P < 0.05) at both “comfortable” (2.27 ± 0.35 vs 1.92 ± 0.21 J kg⁻¹ m⁻¹) and “fast” speed (3.05 ± 0.35 vs 2.37 ± 0.42 J kg⁻¹ m⁻¹). CMT1A patients, therefore, choose to walk slower but with higher metabolic cost compared to healthy individuals, despite no clinically evident walking impairment, which is likely due to altered walking patterns.

Introduction

Charcot Marie Tooth disease (CMT), also referred to as hereditary motor and sensory neuropathy (HMSN), is a genetic and progressive neuropathy affecting from 10 to 30 per 100,000 people in the world [1], [2]. CMT1A, which is the most frequent form of CMT1 (60–80% of total cases, [3]), is characterised by segmental demyelination, reduction of the nerve conduction velocity of peripheral nerves and consequent axonal degeneration that impair functions of the distal part of legs and arms [4], [5]. CMT1A patients show a decline in motor performances due to loss of muscle strength [6], [7], [8], [9], fatigue or experienced fatigue [10], [11], [12], [13], foot and ankle deformities and alteration of balance [1], [2], [5], [14], [15], [16], pain [17], [18], [19], [20] reduction of functional aerobic capacity [6], [21] and, as a consequence, low levels of daily activity [22], [23], [24].

It has been recently demonstrated by Padua and colleagues [20] that in CMT1A patients the ability to ambulate independently is the motor skill most positively affecting the perceived quality of life, as assessed by means of questionnaires. Patterns of walking in CMT patients have been extensively described by means of motion analysis especially on severely impaired patients. These studies highlighted that the principal limits of CMT walking are instability of the ankle on a sagittal plane [25], increase in plantar flexion during the initial contact [26], [27], higher dorsi flexion during the stand phase [26], [28] and loss of active push off [25], [26], [27], higher knee and hip flexion [26] and the asymmetric hip movement in medio-lateral plane, hip elevation [26], [29], [30] and decrease in hip adduction [26], [27], [30].

Don and colleagues [26] have attempted to estimate the energy expenditure based on mechanical behaviour of the body in terms of energy recovery and energy consumption in relation to the whole body centre of mass. They have shown that CMT patients with foot drop have a higher walking energy cost, which is related to the mechanical effort to perform a marked knee and hip flexion. On the other hand, despite a gait with hip abduction and pelvic elevation, the walking energy cost is lower in patients with plantar flexor failure. To the best of the authors’ knowledge there are no studies on the metabolic cost of walking in this population. The measurement of walking energy cost per unit of distance (WECd), also referred to as walking economy, is a valid indicator of walking performance. Individuals with good walking economy, from a practical perspective, walk faster and for longer with a lower level of physical effort [31], [32]. Moreover, WECd is a quantitative and reliable method able to detect even minor walking impairment [33], [34] and it has been used to determine walking economy on a number of patients with various pathological conditions [35], [36], [37], [38], [39]. Similarly, the heart rate per unit of distance (HRd), also referred to as cardiac cost, correlates with WECd and, although less accurate, has been used as an indicator of the cost of walking [31], [32].

In CMT1A patients who are only moderately impaired, quantifying the level of walking impairment by means of WECd and HRd might be highly relevant for assessing the effect of specific interventions designed to improve their walking ability. The purpose of this study is therefore to quantify the walking energy and cardiac costs of patients with CMT1A, with low severity of walking impairment, in comparison with healthy individuals. It is hypothesised that patients with CMT1A have a higher metabolic and cardiac cost of walking with respect to healthy individuals despite the lack of clinically evident walking impairment.