Energetic cost of walking and spasticity in persons with multiple sclerosis with moderate disability

Abstract

BACKGROUND:

The energetic cost of walking (C_w) is elevated in persons with multiple sclerosis (MS). This may be explained by spasticity and spatiotemporal parameters of gait.

OBJECTIVE:

To examine the associations among C_w, spasticity of ankle plantarflexors, and spatiotemporal gait parameters in persons with MS who had moderate disability.

METHODS:

The sample included 44 persons with MS who had moderate disability. C_w was measured over-ground during the 6-Minute Walk using indirect calorimetry and was calculated based on net oxygen consumption and walking speed (i.e., expressed ml·kg^–¹·m^–¹). Participants underwent the Modified Ashworth Scale as a measurement of spasticity and performed 4 trials of walking on a GAITRite electronic walkway for measurement of spatiotemporal gait parameters.

RESULTS:

Spasticity was positively correlated with C_w (r = 0.52, p < 0.05) and inversely correlated with cadence (r = –.45, p < 0.05) and step length (r = –0.40, p < 0.05). Cadence (r = –0.59, p < 0.05) and step length (r = –0.56, p < 0.05) were inversely correlated with C_w. The regression analysis indicated that spasticity explained significant variance in C_w, and cadence and step length accounted for the association.

CONCLUSIONS:

These results suggest that worse spasticity of the ankle plantarflexors and slower cadence and shorter step length, in turn, are responsible for elevated C_w among persons with MS with moderate disability. This supports the development of therapeutic, rehabilitation interventions delivered by clinicians for managing spasticity and the resulting C_w that may interfere with activities of daily living.

Keywords

Multiple sclerosis energy expenditure spasticity walking rehabilitation

1 Introduction

Multiple sclerosis (MS) is a chronic neurological disease characterized by immune-mediated demyelination and neurodegenerative processes (i.e., axonal transection and neuronal loss) in the central nervous system (CNS) (Trapp & Nave, 2008). The disease process manifests as white and gray matter damage in the CNS and results in mobility disability (Motl, 2010). Walking impairment is one of the most ubiquitous and life-altering consequences of MS and worsens as a function of increasing mobility disability (Larocca, 2011; Motl et al., 2017). Walking impairment may become particularly problematic when it co-occurs with an increase in energetic cost of walking (C_w). C_w (i.e., the amount of oxygen consumed per kilogram of body weight per unit distance walked) is a physiological marker of walking impairment that reflects the contributions of pathological gait abnormalities and other manifestations caused by disability (Waters & Mulroy, 1999). There is evidence that persons with MS have higher C_w than persons without MS (Chung, Angelo, van Emmerik, & Kent, 2016; Motl et al., 2011), and that among persons with MS, those with worse walking impairment demonstrated higher C_w measured during both treadmill and over-ground walking (Motl et al., 2011). One subgroup of persons with MS that has been identified to have particularly elevated C_w involves those who have reached the onset of moderate mobility disability (i.e., Expanded Disability Status Scale [EDSS] scores ≥ 4.0). Elevated C_w associated with moderate MS-related mobility disability might lead to reduced participation in daily activities and possibly increased perceptions of fatigue (Motl, Sandroff, Suh, & Sosnoff, 2012). Such observations support the importance of research that identifies factors associated with C_w for informing the design of future rehabilitation interventions that target a reduction in walking impairment and its consequences among persons with MS.

Spasticity (i.e., velocity-dependent increase in muscle resistance in response to a passive stretch) is a common symptom of MS and may influence C_w (Johnson, 2002). Spasticity is linearly associated with mobility disability and is most prevalent in the ankle plantarflexors (Hoang, Gandevia, & Herbert, 2014; Rizzo, Hadjimichael, Preiningerova, & Vollmer, 2004). For example, persons with MS who have spasticity of ankle plantarflexors have demonstrated reduced walking performance based on the 6-Minute Walk (6 MW), Timed 25-Foot Walk (T25FW), and Timed Up and Go (TUG) compared with those who do not have spasticity (Olgiati, Burgunder, & Mumenthaler, 1988; Sosnoff, Sandroff, & Motl, 2012). Spasticity of the ankle plantarflexors further has been associated with higher C_w while walking on a treadmill in a small sample of 33 persons with MS who had mild disability (Olgiati et al., 1988). Of note, C_w measured on a treadmill may not be comparable to that of over-ground walking in persons with MS (Motl et al., 2011). There is minimal research examining spatiotemporal gait parameters (i.e., cadence and step length) as possible factors accounting for the relationship between plantarflexor spasticity and C_w in persons with MS who have moderate mobility disability.

The association between spasticity of the ankle plantarflexors and C_w may be explained by alterations in spatiotemporal gait parameters (Haselkorn & Loomis, 2005; Thompson, Jarrett, Lockley, Marsden, & Stevenson, 2005). One study indicated that persons with MS who have spasticity demonstrate reduced walking velocity, cadence, and step length compared with those who do not have spasticity (Pau, Coghe, Corona, Marrosu, & Cocco, 2015). There further is evidence of an inverse relationship between spatiotemporal gait parameters and C_w (Motl et al., 2012). Cadence, in particular, has explained the association between disability status and C_w (Sandroff, Klaren, Pilutti, & Motl, 2014). Collectively, such a pattern of results suggests that spasticity may influence C_w and ultimately mobility disability through alterations in gait parameters. However, we are unaware of direct examinations of C_w and its associations with spasticity and spatiotemporal gait parameters in persons with moderate MS mobility disability.

The current study examined the associations among C_w, spasticity of the ankle plantarflexors, and spatiotemporal gait parameters in persons with MS who had moderate mobility disability based on scores between 4.0 and 6.0 from the EDSS (i.e., a benchmark of moderate mobility disability indicative of the 2nd stage of MS), as this group has a level of disability wherein disease-modifying medications have limited influence on manifestations such as walking impairments and C_w (Confavreux, Vukusic, & Adeleine, 2003). We hypothesized that higher levels of spasticity of the ankle plantarflexors would be associated with higher C_w measured during over-ground walking. We further hypothesized that higher levels of spasticity would be associated with worse alterations in spatiotemporal gait parameters, particularly cadence and step length, and that the alterations in spatiotemporal gait parameters would account for the association between spasticity of the ankle plantarflexors and C_w. If our hypotheses are correct, such preliminary evidence would highlight the importance of developing therapeutic, rehabilitation interventions for eventual inclusion in clinical practice for managing spasticity as an approach for reducing C_w and ultimately walking impairment by improving gait. Such interventions may result in secondary benefits including management of fatigue and improvement in quality of life in persons with moderate MS.

2 Methods

2.1 Participants

The participants were recruited through direct contact with support groups of a Midwestern chapter of the National Multiple Sclerosis Society that were located with an approximately 90-minute drive of the testing facility. The inclusion criteria involved (a) medical diagnosis of MS; (b) EDSS score between 4.0 and 6.0 confirmed based on the participants’ neurologist; (c) relapse-free during the past 30 days before testing; (d) ambulation without an assistive device including cane, crutch or walker; (e) willingness to complete the walking assessments; and (f) low risk for contraindications of physical activity based on no more than a single “yes” response on the Physical Activity Readiness Questionnaire (PAR-Q) (Thomas, Reading, & Shephard, 1992).

The sample had a mean (standard deviation, SD) age of 48 (8.6) years and was predominantly female (86%). The mean height and weight were 168 (8.8) centimeters and 84 (25.2) kilograms, respectively. The median (interquartile range, IQR) PDDS score was 5.5 (2.5) indicating that the sample had moderate mobility disability (Learmonth, Motl, Sandroff, Pula, & Cadavid, 2013).

2.2 Outcome measures

2.2.1 Spasticity

Spasticity of the ankle plantarflexors of both legs were measured by a physical therapist using the modified Ashworth scale (MAS). The MAS provides a measure of muscle hypertonia on a five-point scale, ranging from 0 (no increase in muscle tone) through 4 (fixed muscle contracture) (Bohannon & Smith, 1987). We averaged the MAS scores for plantarflexors of both legs for the data analysis. This was based on providing a global measure of spasticity of the plantarflexors, and the observation that the MAS score of the most affected leg correlated with the average MAS score (r = 0.97). The intraclass correlation for MAS scores from the right and left legs was.90 and further supported the formation of an average MAS score.

2.2.2 Energetic cost of walking

C_w was measured during the 6 MW using a portable, indirect calorimetry system (K4b2 Cosmed, Italy). The O₂ and CO₂ analyzers and flowmeter of the portable metabolic unit were calibrated, as per manufacturer’s recommendations. We measured oxygen consumption for an estimate of resting metabolic function, expressed as the average of two, 30-second values over the last minute of an initial five-minute period of seated rest (i.e., resting-state VO₂). Participants then underwent the 6 MW with standardized instructions of walking as far and as fast as possible for six minutes while wearing the portable calorimetry system for VO₂ measurement. Total distance traveled (m) was measured using a calibrated measuring wheel (Stanley MW50, New Briton, CT). We measured net steady-state VO₂ as the difference between average VO₂ during the last three minutes of the 6 MW (i.e., steady-state VO₂) and average resting-state VO₂ values. C_w was then expressed as ml·kg^–¹·m^–¹ by dividing net steady-state VO2 in ml·kg^–¹·min^–¹ by actual 6 MW speed in m·min^–¹ (C_w = (steady-state VO₂ – resting VO₂) / speed); we operationalized steady-state VO₂ as the last three minutes of the 6 MW based on previous research regarding the pattern of oxygen kinetics during the 6 MW in MS and our current data wherein steady-state was clearly obtained by 180 seconds of the 6 MW.

Fig. 1.

Oxygen consumption over a six-minute walk test in the sample of persons with MS (n = 44). The dashed line indicates the achievement of steady-state VO₂.

2.2.3 Gait parameters

Participants completed 4 trials of walking on a 16-foot GAITRite (CIR systems, Inc, Havertown, Pennsylvania) electronic walkway at a comfortable pace as done in previous research involving persons with MS (Sosnoff, Gappmaier, Frame, & Motl, 2011; Sosnoff et al., 2012). The GAITRite system is a computerized instrumented mat with sensors arranged in a grid-like pattern for identifying footfall contacts. We recorded cadence (steps/min) and step length (cm) per trial based on previous research involving gait and C_w in MS (Sosnoff et al., 2012), and the average of the 4 trials was used in the data analysis.

2.2.4 Disability status

Participants completed the Patient Determined Disease Steps (PDDS) as an adjuvant for confirming the EDSS inclusion criterion (Marrie & Goldman, 2007). PDDS scores range between 0 (normal) and 8 (bedridden), and the scores have been validated as a measure of disability status in persons with MS (Learmonth et al., 2013).

2.3 Procedure

The procedure was approved by a University Institutional Review Board, and all participants provided written informed consent. Participants completed a demographic scale, underwent a measurement of spasticity of the ankle plantarflexors using the Modified Ashworth Scale (MAS) by a physical therapist, and performed 4 trials of walking on the GAITRite electronic walkway for measuring spatial and temporal parameters of gait followed by 10 minutes of seated rest. We measured height and weight using a scale stadiometer. Participants were then fitted with the portable metabolic system during the seated rest. Once wearing the system and ensuring normal, resting metabolic function, participants were given standardized instructions for undertaking the 6 MW test. All participants were remunerated $50 for completing the session.

2.4 Statistical analysis

All data analyses were performed using Statistical Package for the Social Science 24.0. We provided descriptive statistics of the measures as mean (standard deviation, SD) unless stated otherwise. The associations among C_w, ankle plantarflexor spasticity, and gait parameters were examined using Pearson product-moment correlation coefficients (r). Values for correlation coefficients were interpreted as small, moderate, and large based on 0.1, 0.3, and 0.5, respectively (Cohen, 1988). To identify if gait parameters (i.e., cadence and step length) accounted for the association between ankle plantarflexor spasticity and C_w in our sample, we performed a hierarchical linear regression analysis wherein we regressed C_w on ankle plantarflexor spasticity in Step 1, followed by stepwise entry of cadence and step length as predictors in Steps 2 and 3, respectively.

3 Results

3.1 Descriptive characteristics

The mean values for ankle plantarflexor spasticity, cadence, step length, and C_w are presented in Table 1. The median (IQR) MAS value of the sample was 1.50 (1.88); this corresponds with a MAS anchor of “slight increase in muscle tone, manifest as a catch and release or resistance at the end of range of motion during passive movement” (Bohannon & Smith, 1987). The mean cadence value was 95.25 (20.26) steps per minute, and the mean step length value was 53.80 (14.75) centimeters. Overall, this sample demonstrated reduced cadence and step length compared with other MS samples (Sandroff, Sosnoff, & Motl, 2013); this was expected as the current sample had moderate mobility disability based on EDSS and PDDS scores. Of note, the mean net C_w value was 0.17 (0.07) ml·kg^–¹·m^–¹; this value is comparable with C_w reported in another sample of persons with a broad range of MS-related mobility disability (Sandroff et al., 2014).

Table 1
Descriptive statistics of spasticity, cadence, step length, and C_w of the sample of persons with MS (n = 44)

Measurement Mean (SD)

MAS 1.59 (1.04)

Cadence (steps/min) 95.25 (20.26)

Step length (cm) 53.80 (14.75)

C_w (ml·kg^–¹·m^–¹) 0.17 (0.07)

Measurement	Mean (SD)
MAS	1.59 (1.04)
Cadence (steps/min)	95.25 (20.26)
Step length (cm)	53.80 (14.75)
C_w (ml·kg^–¹·m^–¹)	0.17 (0.07)

Note: Mean (SD); MAS, Modified Ashworth Scale.

3.2 Bivariate correlation analysis

The bivariate associations among spasticity, cadence, step length, and C_w are provided in Table 2. Spasticity was positively correlated with C_w (r = 0.52, p < 0.05) and inversely correlated with cadence (r = –0.45, p < 0.05) and step length (r = –0.40, p < 0.05). Cadence (r = –0.59, p < 0.05) and step length (r = –0.56, p < 0.05) were inversely correlated with C_w. Collectively, this indicates that those with greater spasticity demonstrated moderately higher C_w, slower cadence, and shorter step length.

Table 2
Summary of correlations among spasticity, cadence, step length, C_w, in the sample of persons with MS (n = 44)

1 2 3 4

1. MAS – – – –

2. Cadence (steps/min) –0.45* – – –

3. Step length (cm) –0.40* –0.40* – –

4. C_w (ml·kg^–¹·m^–¹) 0.52* –0.59* –0.56* –

	1	2	3	4
1. MAS	–	–	–	–
2. Cadence (steps/min)	–0.45*	–	–	–
3. Step length (cm)	–0.40*	–0.40*	–	–
4. C_w (ml·kg^–¹·m^–¹)	0.52*	–0.59*	–0.56*	–

Note: MAS, Modified Ashworth Scale; *p<0.05, two-tailed test.

3.3 Regression analysis

The results of the regression analyses are provided in Table 3. The first model indicated that ankle plantarflexor spasticity had a significant association with C_w and explained 27.2% of variance in C_w (R² = 0.272, p < 0.01; F_{1, 43} = 15.73, p < 0.01) (Step 1). Cadence entered into the equation in Step 2 (ΔR² = 0.162, p < 0.01), and the model explained 43.5% of variance in C_w (R² = 0.435, p < 0.01; F_{2, 42} = 15.77, p < 0.01). Both cadence and step length entered into the equation in Step 3 (ΔR² = 0.066, p < 0.03), and the model explained 50.1% of variance in C_w (R² = 0.501, p < 0.05; F_{3, 40} = 13.40, p < 0.00). The standardized beta-coefficient between C_w and ankle plantarflexor spasticity in Step 1 was attenuated and non-significant when controlling for cadence and step length in the model in Steps 2 and 3.

Table 3
Summary of regression analysis for spasticity, cadence, and step length predicting C_w in the sample of persons with MS (n = 44)

C_w

B SE B β

Step 1

MAS 0.039 0.010 0.522*

Note: R² = 0.272 for model (p < 0.01)

Step 2

MAS 0.024 0.010 0.320*

Cadence –0.002 0.000 –0.451*

Note: R² = 0.435 for model (p < 0.01)

Step 3

MAS 0.018 0.010 0.248

Cadence –0.001 0.001 –0.339*

Step length –0.002 0.001 –0.302*

Note: R² = 0.501 for model (p < 0.05).

	C_w
Step 1
MAS	0.039	0.010	0.522*
Note: R² = 0.272 for model (p < 0.01)
Step 2
MAS	0.024	0.010	0.320*
Cadence	–0.002	0.000	–0.451*
Note: R² = 0.435 for model (p < 0.01)
Step 3
MAS	0.018	0.010	0.248
Cadence	–0.001	0.001	–0.339*
Step length	–0.002	0.001	–0.302*
Note: R² = 0.501 for model (p < 0.05).

Note: MAS, Modified Ashworth Scale; *p<0.05; B Unstandardized Beta, SE B Standard Error of Beta, β Standardized Beta.

4 Discussion

This study examined the association between ankle plantarflexor spasticity and C_w in persons with MS who had moderate mobility disability, and further examined spatiotemporal gait parameters as possible factors that accounted for the association between spasticity and C_w. The bivariate correlation analysis indicated that persons who had higher levels of spasticity in the ankle plantarflexors demonstrated higher C_w during a 6-minute period of walking, as well as slower cadence, and shorter step length under normal walking conditions. The regression analysis indicated that ankle plantarflexor spasticity explained significant variance in C_w in persons with MS who had moderate mobility disability, and cadence and step length accounted for this association. Such results suggest that worse spasticity is associated with higher C_w possibly through altered spatiotemporal gait parameters and identify spasticity of the ankle plantarflexors as a target for subsequent therapeutic rehabilitation interventions for reducing C_w and improving gait among those with the onset of moderate MS-related mobility disability.

Spasticity of the ankle plantarflexors was significantly associated with C_w measured during over-ground walking in the present sample of persons with moderate MS. To our knowledge, this study is the first to examine spasticity and C_w during over-ground walking in those who have moderate mobility disability based on EDSS scores between 4.0 and 6.0 and then confirmed with PDDS scores. One previous study identified an association between spasticity and C_w on a treadmill in thirty-three persons with mild MS (Olgiati et al., 1988), but did not include a standard, clinical measure of spasticity. We extended that research by including persons with moderate MS who undertook over-ground walking, and our results confirm this association between a clinically-relevant measure of ankle plantarflexor spasticity and C_w. MS-related spasticity that occurs during walking may increase C_w based on varying displacement of center of gravity during walking, resulting in a less efficient walking pattern. As such, the current results suggest that management of ankle plantarflexor spasticity may be a target for possibly reducing C_w in MS.

Spasticity of the ankle plantarflexors was associated with alterations in cadence and step length in the present sample of persons with moderate MS-related mobility disability. This is consistent with results from a previous study in MS that reported that nineteen persons with MS who had moderate-to-severe spasticity in the plantarflexors demonstrated reduced cadence and stride length measured by a 3D motion analysis system (Pau et al., 2015). Indeed, the present results extend this relationship by demonstrating associations among spasticity, cadence/stride length, and C_w among persons with moderate MS-related mobility disability. This further supports the observation of altered gait parameters in persons with MS who have EDSS scores between 4.0 and 6.0 (Pilutti et al., 2013). We speculate that persons with MS within this range who demonstrate slower cadence and shorter stride length may do so, in part, because of higher levels of spasticity. As previous studies have reported, the presence and severity of spasticity is significantly associated with disability status (Rizzo et al., 2004), which suggests that alterations in gait parameters may be more distinctive and detrimental as disability worsens. This underscores the importance of designing interventions for the management of spasticity for maintaining or improving gait parameters.

Cadence and step length were associated with C_w in this sample of persons with MS who had moderate mobility disability, and this is consistent with previous research. For example, a previous study reported an association between cadence and C_w measured on a treadmill in forty-four persons with mild MS (Motl et al., 2012). We have extended the results of previous research by demonstrating that cadence and stride length were associated with C_w measured during over-ground walking in persons with MS who have moderate mobility disability. We do note that our protocol involved walking over-ground, as opposed to on a treadmill, as this better reflects free-living walking in persons with MS. Nevertheless, the current pattern of results is consistent with the notion that C_w reflects the overarching contribution of disability on walking impairments in neurological diseases (Waters & Mulroy, 1999).

The primary novel findings were that ankle plantarflexor spasticity was associated with C_w, and that cadence and step length explained the association between spasticity and C_w. The identification of cadence and step length as intervening variables of the association between spasticity and C_w may be attributed to inefficient walking patterns resultant from spasticity of the plantarflexors, which may, in turn, reduce cadence and step length. This indicates that altered spatiotemporal gait parameters might result in the energetic penalty of walking brought upon by spasticity in those with MS who have moderate mobility disability. The current results support the development of interventions for managing spasticity and, in turn, improving cadence and step length to minimize the C_w in MS, particularly those with moderate mobility disability that is characteristic of the 2nd stage of the disease.

There are limitations that should be considered when interpreting the results of this study. One limitation includes the cross-sectional study design, which does not provide longitudinal data on the management of spasticity and alterations of gait parameters on C_w. Another limitation of the study is that we did not include other variables that may have affected gait in MS aside from spasticity of the ankle plantarflexors as potential covariates; this was based on the hypothesis that gait and spasticity are major contributors of C_w and the lack of exploratory research for identifying the possible variables explaining C_w in MS. We note that future research efforts might consider identifying and controlling for such potential covariates when examining the effects of gait on C_w in persons with MS. However, spasticity is commonly observed in persons with MS and has been reported to result in negative consequences on mobility and balance (Rizzo et al., 2004; Sosnoff et al., 2011). The study further does not indicate causality among ankle plantarflexor spasticity, spatiotemporal gait parameters, and C_w, but does provide preliminary data that is precursory for designing an intervention that targets the management of spasticity and gait rehabilitation for reducing C_w. One final limitation involves a relatively small sample size that was specifically recruited based on having the onset of moderate MS-related mobility disability, which limits the generalizability among those with mild or severe MS.

The present study reported that spasticity of the plantarflexors was associated with higher C_w and that spatiotemporal gait parameters account for this association in persons with MS who have moderate mobility disability. Both spasticity and gait parameters were associated with C_w, and cadence and step length explained the association between spasticity and C_w. Collectively, these results suggest that worse spasticity of the plantarflexors and slower cadence and shorter step length, in turn, are responsible for elevated C_w among persons with moderate MS. This supports the application of an intervention for managing spasticity to possibly reduce C_w that may interfere with activities of daily living in persons with MS.

Conflict of interest

None to report.

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	C_w
	B	SE B	β
Step 1
MAS	0.039	0.010	0.522*
Note: R² = 0.272 for model (p < 0.01)
Step 2
MAS	0.024	0.010	0.320*
Cadence	–0.002	0.000	–0.451*
Note: R² = 0.435 for model (p < 0.01)
Step 3
MAS	0.018	0.010	0.248
Cadence	–0.001	0.001	–0.339*
Step length	–0.002	0.001	–0.302*
Note: R² = 0.501 for model (p < 0.05).