Abstract
Introduction
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that irreversibly affects the motor neurons (Mitchell & Borasio, 2007). The progressive loss of muscle force (MF) reduces the capacity to walk as the disease advances (Slavin, Jette, Andres, & Munsat, 1998). The gait and functional activitiesof the lower limbs (LLII) may be evaluated by the mobility domain of the Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40). Mobility depends on both muscle force and amplitude of active movement (AAM). These two measurements are progressively affected as the disease evolves. The influence each of these has on mobility is still not clear, but there is evidence that the force of the LLII interfere in the temporal characteristics of gait (Goldfarb & Simon, 1984).
The AAM in the mobility of subjects with ALS is an underused measurement, due to the lack of evidence about the relevance of this datum. In spite of this, there are indications pointing out that individuals with neuromuscle disorders produce less force as the knee angle increases (Gerrits, Gommans, van Engelen, & de Haan, 2003). The difficulty of performing complete AAM in ALS is due to muscle weakness. An indirect manner of evaluating weakness is by means of the AAM of the LLII. This evaluation format appears to be more compatible with the ability to walk, because it identifies the submaximal forces in a functional activity. During gait, the different muscle groups exert submaximal forces that do not generate physical effort in the healthy population (Ogawa et al., 2015). In ALS, however, the rates of fatigue in gait may be found at an early stage (Mohammed Sanjak, Bravver, Bockenek, Norton, & Brooks, 2010). This fact is correlated with postural instability (Sugavaneswaran, Umapathy, & Krishnan, 2012) and with slowdown in protective postural reactions (Wu & Shi, 2011). To minimize this effort and increase the functionality of gait, subjects with ALS tend to diminish the step length (Goldfarb & Simon, 1984) and make movements with low amplitude. Gait becomes slow and the level of attention demanded during gait increases (Inam, Vucic, Brodaty, Zoing, & Kiernan, 2010). This is a common strategy in individuals with muscle weakness and does not depend on the base disease. In view of the foregoing, the aim of this study was to analyze the influence of MF and AAM of the lower limbs on the mobility of subjects with ALS.
Subjects and methods
Subjects
Twenty-three (23) individuals with definitive or probable diagnosis of ALS, in accordance with the criteria of the Revised El Escorial (Brooks, Miller, Swash, & Munsat, 2000). The subjects included were those in stages I to III of the scale of ALS/HSS disease severity (Riviere, Meininger, Zeisser, & Munsat, 1998). Excluded from the study were individuals who presented bulbar compromise, sensory neuropathies, orthopedic surgery of the lower limbs, central neurological diseases or psychiatric disturbances described on the medical record chart. Data were collected at the outpatient clinic of Motor Neuron Diseases (MND) of the University Hospital of the Federal University of Bahia (HUPES) during the months of June and August 2012. The research complied with the ethical principles of Resolution 196/12 of the National Health Council of Brazil, and all the participants signed the Term of Free and Informed Consent. The project was approved by the hospital’s Ethics Committee, Protocol No. 025/11.
Collection protocol
Data collection occurred during a consultation scheduled with the multidisciplinary team. The procedures were performed by a single experienced examiner who was familiar with the collection instruments. The collection protocol consisted of application of the questionnaire and physical examination. This procedure was performed in a restricted, acclimatized room.
Initially, the questionnaires were applied in a face-to-face interview in a structured format. For this purpose, the subjects were comfortably seated on chairs, and the interview began after familiarization with the environment and explanation about the procedures. The instruments used were the sample characterization form and ALSAQ-40 (Pavan et al., 2010). This instrument is composed of five domains: mobility (MOB), daily life activities (DLA), eating (EAT), communication (COM) and emotional status (EMO) that have independent scores. In this study, only the mobility domain was used. This domain has 10 questions directed towards the individual’s condition in the previous two weeks. The responses are graded by a Likert scale, in which: 0 “Presents no difficulty”; 1 “Rarely presents difficulty”; 2 “Sometimes presents difficulty”; 3 “Frequently presents difficulty” and 4 “Always presents difficulty”. The MOB domain indicates the degree of compromise with a score of 0 (mobility completely preserved) to 100 (worst possible mobility – restricted to bed).
Afterwards the maximum force and amplitude of movement of the most affected lower limb were evaluated. The most affected limb was identified by means of the manual muscle test of the quadriceps and Tibialis anterior muscle, bilaterally. The lower limb with the lowest score was selected. The knee flexors and extensors, and plantar and dorsal flexors of the ankle were selected. This group of muscles was recommended in the Accurate Test of Limb Isometric Strength (ATLIS) (Andres et al., 2012). Force was obtained by one maximum voluntary isometric contraction (MVIC).
MVIC was collected with the aid of a metal dispositive developed for this purpose. The equipment was based on a model proposed by the authors who developed ATLIS (Andres et al., 2012). The load cell was coupled to the equipment and sent the signal to the signal-conditioning module with four channels (EMG System, Brasil). To evaluate the knee flexors and extensors, the subject was seated with trunk erect, knee flexed at 90° and feet hanging down. All used the backrest belt to stabilize the trunk. The load cell was placed on an adjustable bar at the base of the structure and fixed to the ankle by means of velcro®. To evaluate the dorsal and plantar flexors, the subjects remained in the same position with their feet supported. The load cell was placed in the superior region of the forefoot for evaluating the dorsal flexors, and in the inferior region for the plantar flexors.
Before collection, a MVIC was performed for the purposes of training and final adjustments. All the subjects performed one MVIC for each muscle group. The mean value obtained in Kgf was considered to analysis. Each contraction was sustained for six seconds, with an interval of two minutes between them. To minimize the possible variations in muscle temperature, the ambient temperature was kept constant at 22°C and the subjects were kept in the room for at least 30 minutes. Each MVIC consisted of a maximum contraction against nonelastic resistance with visual feedback and verbal stimulation from the researcher. The data generated were analyzed by using EMGLab FULL V.2 software (EMG System, Brazil) and treated by discarding the first and the last seconds values.
The amplitudes of movement selected were hip and knee flexion. To collect these data, the electrogoniometer (EMG System, Brazil) was used, coupled to the signal conditioner module from the same manufacturer. The individuals were placed in the position of orthostasis and asked to perform active flexion of the hip up to maximum amplitude, and afterwards knee flexion. The angles obtained were recorded and filed.
Data analysis
The sample characterization variables were presented by means of frequencies, central tendency and dispersion measurements. Muscle force and amplitude of movement were considered continuous variables. The Shapiro-Wilk test was applied to verify adhesion of the mobility, muscle force and amplitude of movement data to the normality curve. To analyze the influence of force and amplitude of movement on mobility the multiple linear regression test was applied. These procedures were performed in the statistical package SPSS 22.0, considering the value of α≤0.05.
Results
The clinical characteristics of the 23 subjects with ALS are described in Table 1. A total of 19 (82.6%) men and four (17.4%) women were evaluated, with a mean diagnostic time of 15.64 (±15.22) months. The larger portion of the participants were in the moderate stage of the disease [13(56.5%)] and 20 individuals (87%) were helped by their caregivers. The mean muscle force and AAM values are also described in this table. The influence of the measurements of force and AAM on mobility was initially verified by means of bivariate correlation. Possible covariables that could interfere in the mobility of subjects with ALS were also analyzed (Table 2).
Among the measures of the physical exam, the force of the dorsiflexors was the only measure that did not demonstrate significance (r = –0.336, p = 0.059). Among the covariables, the only one that exhibited significant association with mobility was the stage of disease (r = –0.508, p = 0.130). This finding allowed the multiple linear regression model to be adjusted according to the stage of the disease.
The model was statistically significant [F (9,13) =5.274, p = 0.004] with adjusted R2 of 0.636, indicating that the variables of the physical exam were responsible for 63.6% of the variation in mobility. In addition the residual standard error (RSE) of this model was found to be 16.565. This information revealed that the values observed in mobility varied, on an average, 26.18′ around the values predicted. The model satisfactorily represented the influence of the physical exam variables on the mobility due to the adjusted R2 being considered high and theRSE low.
In spite of the strong correlation between the variables of the physical exam and mobility, the only variable that significantly explained this was the AAM of hip flexion (t = –3.332, p = 0.005). All the muscle forces and AAM of knee flexion demonstrated no significant levels of t (Table 3).
This result revealed that the AAM of hip flexion was a safe predictor of mobility of subjects with ALS. The maximum force of the knee flexors and extensors presented low predictive power of mobility with levels of t, respectively. The plantar and dorsiflexors also presented low predictive power of mobility with levels of t [(t = –0.206, p = 0.804) / (t = –0.548, p = 0.596)], respectively.
Discussion
Maximum force and Amplitude of Active Movement of the lower limbs are correlated with mobility in subjects with ALS. However, the variation in mobility was basically due to the AAM of hip flexion. This finding demonstrated statistical consistency and was in agreement with the expectations of the authors who expected to find significant influence of muscle force on mobility. Rehabilitation Centers use it as a marker of disease evolution (Qureshi, Schoenfeld, Paliwal, Shui, & Cudkowicz, 2009), as in the study of Slavin et al. (1998), who collected the maximum force of the dorsiflexors, and knee and hip flexors and extensors in 240 subjects with ALS (Slavin et al., 1998).
The force of the knee flexors had an influence on walking in community, and on the force of hip extensors on walking at home. When applying a regression equation to predict the maximum force based on age, gender and weight, a strong association was verified between the force of the lower limbs and walking that was not shown in the present study. In a subsample of 118 subjects, it was pointed out that the levels of force demanded differed between subjects who walked in the community and at home (Jette, Slavin, Andres, & Munsat, 1999). In this same study, composed of 532 subjects with ALS, it was concluded that the force of proximal muscles interfered more in walking than in the force of distal muscles (Andres, Slavin, & Jette, 1997). The present study corroborates these findings on demonstrating low correlation between the force of dorsiflexors and mobility. The differences in methodology and sample size made comparability of the study difficult and may justify the divergence in the findings related to force.
The importance of muscle force in clinical practice may be verified the protocols of evaluation of the disease. The TUFS quantitative neuromuscular exam (TQNE) is a global protocol for the evaluation of force in the ALS (P L Andres et al., 1986). Later, this exam was denominated ATLIS using fewer muscles and providing greater accuracy (Patricia L Andres et al., 2012). Based on this resource, the authors validated the equation for the prediction of force according to sex, age and weight (Patricia L Andres et al., 2013). The severity of muscle weakness depends on the difference between the collected and predicted value.
The present study used the ATLIS protocol for evaluating the force of LLII. This exam uses the MVIC for capturing the maximum force that could be generated by the muscle. The low predictive power of force in the present study was basically due to the way in which it was captured. The questions in the mobility domain of ALSAQ-40 are related to the submaximal forces in functional activities. There are no questions directed to maximum force. The values captured in the MVICs indicated the degree of evolution of the disease, and the effect of an intervention on the force (Cudkowicz, Zhang, Qureshi, & Schoenfeld, 2004), but in the present study, they were incapable of predicting the effects on the mobility of subjects.
Mobility may be understood as the capacity to move in different environments. Gait and functional activities such as climbing up and down stairs, sitting, getting up, squatting comprise mobility. The level of force necessary to perform these functions is considered submaximum and cause low physical force in the healthy population (Ogawa et al., 2015). However, in subjects with ALS, these activities cause greater overload and may lead to early fatigue (M Sanjak et al., 2001). A protective mechanism for minimizing wear during gait is to reduce the step length (Goldfarb & Simon, 1984). Greater amplitudes mean greater muscle recruitment. Therefore, subjects with ALS tend to diminish articular amplitudes with the purpose of remaining functional for a longer time. Hence, reduction in articular amplitudes reduces the capacity of movement of these subjects. This evidence may be found in different neurological diseases, such as Parkinson and Huntington disease (Hausdorff et al., 2000).
The reduction in AAM in functional activities is a common biomechanical adaptation in muscle weakness, irrespective of the disease. For example, the quadriceps of subjects with Nemaline Myopathy (NM) produce force similar to that of healthyindividuals when the MVIC was captured at low amplitudes of the knee (Gerrits et al., 2003). As the angle increased, the capacity to generate force diminished in individuals with NM. This means that the disease imposes a mechanical disadvantage on activities with greater articular amplitude of the lower limbs. This finding is compatible with the functional loss in motor neuron diseases. Gait and orthostasis are generally affected after significant compromise, in activities with greater AAM, such as sitting down, getting up and climbing stairs. The activities with greater articular amplitude demand more muscle recruitment. This reason justifies the progressive reduction of articular amplitudes during gait through to functional inability in ALS (Radovanović et al., 2014).
Only hip flexion demonstrated important influence on the mobility of subjects with ALS. The action of the hip during gait appears to explain this finding. To begin gait it is necessary to have active flexion of the hip. Higher amplitudes demand muscle control the subject with ALS is incapable of offering. In other neurological diseases the neuromuscular and skeletal systems promote compensations that guarantee the starting of gait. In subjects with sequelae of stroke there is recruitment of the Quadratus Lumborum and anterior rotation of the ipsilateral pelve, generating scissor gait (Chen, Patten, Kothari, & Zajac, 2005). In ALS, the strategies are limited by the generalized muscle weakness. What occurs in ALS is an increase in instability of the center of gravity (Sugavaneswaran et al., 2012) and slowdown of protective postural reactions (Wu & Shi, 2011), making it difficult to begin walking.
In view of the foregoing, the authors were able to conclude that the AAM of hip flexion was a safe predictor of mobility of subjects with ALS. The more severe the compromise, the greater would be the loss of mobility. Weakness of the hip flexors reduces the articular amplitude during functional activities that affect the capacity of movement in ALS. Retarding the functional compromise of hip flexors may keep these subjects functional for a longer time. The maximum force of dorsiflexors, knee flexors and extensors were not shown to be a predictor of mobility in these individuals. Therefore it is not possible to use the values obtained in MVICs to predict the degree of mobility in ALS. The submaximum force appears to be a more objective measurement of the mobility of these subjects. The future perspective is the validation of normative values of AAM of the hip that may rapidly and objectively indicate the degree of compromise of mobility in ALS.
Conflict of interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.