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Gait pattern in Duchenne muscular dystrophy
Gait & Posture 29 (2009) 36–41
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Gait & Posture journal homepage: www.elsevier.com/locate/gaitpost
Gait pattern in Duchenne muscular dystrophy Maria Grazia D’Angelo a,1,*, Matteo Berti a,1, Luigi Piccinini a, Marianna Romei a, Michela Guglieri a,b, Sara Bonato a, Alessandro Degrate a, Anna Carla Turconi a, Nereo Bresolin a,b a b
IRCCS E. Medea, NeuroRehabilitation Department, via don Luigi Monza 20, 23842 Bosisio Parini, Lecco, Italy Institute of Neuroscience, University of Milano, IRCCS Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, via F. Sforza 35, Milano, Italy
A R T I C L E I N F O
A B S T R A C T
Article history: Received 23 July 2007 Received in revised form 23 May 2008 Accepted 9 June 2008
We investigated the gait pattern of 21 patients with Duchenne muscular dystrophy (DMD), compared to 10 healthy controls through 3D Gait Analysis. An overall observation of gait pattern in our DMD patients when compared to controls confirmed the data previously reported for small dystrophic groups. An excessive anterior tilt of pelvis and abnormal knee pattern in loading response phase were found. Since during the swing phase the DMD foot is too plantarflexed, patients adopt a higher flexion and abduction of the hip in order to advance the swinging limb. Velocity and cadence of DMD patients resulted similar to those calculated for healthy subjects, whereas stride length was reduced and step width was increased. We then divided the DMD patients in to two subgroups (treated with steroids and untreated), and we observed that the only statistically significant differences between the two groups in Gait Analysis parameters were found for the maximum of ankle power. 3D Gait Analysis gives objective and quantitative information about the gait pattern and the deviations due to muscular situation of DMD subjects; being our study a single moment evaluation, it is otherwise unable to unravel changes only detectable through serial analysis during the time course of the disease and, if any, due to the treatment. ß 2008 Elsevier B.V. All rights reserved.
Keywords: Gait Analysis Duchenne muscular dystrophy Steroids treatment Ambulation Biomechanics
1. Introduction Duchenne muscular dystrophy (DMD) is the commonest childhood muscular dystrophy with a worldwide incidence of 1 in 3500 male live births. It is an X-linked recessive disorder, due to mutations in the dystrophin gene. Untreated, boys with DMD become progressively weak during their childhood and stop ambulation at a mean age of 9 years. Confinement to a wheelchair is followed by the development of scoliosis, respiratory failure and cardiomyopathy. Without intervention, the mean age at death is 19 years [1,2]; no curative treatment is known. Some studies have reported substantial long-term functional benefits from the steroid therapy: prolonged ambulation into the mid-teens, reduced severity of scoliosis, major preservation of respiratory and cardiac function [3–18] reflected by changes in weakness, which affects the proximal muscle groups first and the distal ones later, compromises the child’s posture and gait. A
* Corresponding author at: NeuroMuscular Unit, IRCCS E. Medea, NeuroRehabilitation Department, via don Luigi Monza 20, 23842 Bosisio Parini (Lecco) Italy, Tel.: +39 031 877870; fax: +39 031 877831. E-mail address: [email protected] (M.G. D’Angelo). 1 These authors equally contributed to the paper. 0966-6362/$ – see front matter ß 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.gaitpost.2008.06.002
dynamic quantitative assessment of gait in DMD patients would be important in evaluating the progression of the disease and the benefits of any therapy [19]. Few studies focused on gait of DMD children [20–23], sample sizes were small and/or not homogenous. The aim of the present study was the characterization of the gait pattern of a large group of DMD children at a single time point of their clinical history compared to healthy age and sex matched controls using three-dimensional Gait Analysis. 2. Materials and methods 2.1. Patients Twenty one DMD children were involved in this study; the diagnosis of DMD was established according to internationally accepted criteria [24]: progressive muscular weakness, increased muscle plasma enzymes, muscle biopsy identifying fiber degeneration and absence of the dystrophin protein, alterations in the dystrophin gene (deletions or other genetic alteration). Exclusion criteria included absence of additional conditions such as cerebral palsy, behavioural and/or psychiatric disturbances, acquired brain or spinal injuries, deafness, severe visual impairment, epilepsy and the ability to walk independently, without aids. Ten healthy children, age and sex matched, were recruited (all boys, mean age: 88.7 14.0 months). Patients and controls did not differ significantly in age, body weight and height (Table 1). Ten out of 21 DMD children began steroids treatment in other hospitals before coming to ours. Four children were under prednisone (0.75 mg/kg day) and six under deflazacort treatment (0.9 mg/kg day) [5,11,15]. Treatment was started at a
M.G. D’Angelo et al. / Gait & Posture 29 (2009) 36–41 Table 1 Means and standard deviations for demographic data Variables
Number of children Age (months) Height (cm) Body weight (kg)
NoT-DMD group
T-DMD group
Control group
11 79.4 33.2 117.5 13.6 22.6 7.8
10 88.0 23.2 120.7 11.6 25.6 9.1
10 88.7 14.0 127.3 7.0 25.0 4.3
Difference
– – –
p-value < .05, compared between NoT-DMD group (NoT: not Treated) and T-DMD group (T: treated).
mean age of 72 8.2 months. At the time of the evaluation the duration of treatment was ranging from 11 to 18 months. We divided the DMD patients in two subgroups: one—treated with steroids (T-DMD) and the other untreated (NoT-DMD) (see Table 1). A second analysis was performed in order to evaluate differences between treated and untreated patients. The mean chronological age of DMD children treated with steroids was 88.0 + 23.2 months and of the untreated ones was 79.4 + 33.2 months. 2.2. Methods The assessment included manual muscle test and three-dimensional Gait Analysis. Manual muscular testing was performed according to the Medical Research Council scale (MRC scale)[25]. Minimal differences in the clinical practice are indicated as ‘‘ ’’ or ‘‘+’’. For the purpose of mean and standard deviation calculations, a grade marked ‘‘ ’’ was considered to be the number of the grade minus 0.33, and a grade marked ‘‘+’’ was considered to be the number of the grade plus 0.33 (for example: 3 = 2.67) [22]. Parents of all children signed a written informed consent form, as approved by the Ethical Committee of our institution. The study was also approved by the Institute’s Human Ethics Committee according to the declaration of Helsinki. The Gait Analysis Laboratory is equipped with an 8-camera optoelectronic system (ELITE2002, BTS, Milan, Italy) working at a sampling rate of 100 Hz for kinematic movement evaluation [26], two force platforms (Kistler Instrument AG, Winterthur, Switzerland) for movement kinetics calculation, and a video recording system (BTS, Milan, Italy) synchronized with the optoelectronic system and force platforms. Markers (spherical retroflective markers: 15 mm in diameter) were positioned according to Davis’ protocol [27]. For data acquisition the subjects were asked to walk barefoot at their own natural pace (self-selected speed) along a walkway (8 m long, 1.5 m wide) where the two force platforms were placed. At least eight trials were collected for each subject in order to ensure the consistency of the data. In order to obtain kinetic data, subjects began their walking from a point, which allowed them to place one foot on the force plate without any modification of cadence or stride length. Only the trials in which the subjects correctly placed their feet on the platforms were considered for the analysis. For each subject, three trials were considered and the data related to left and right limbs were calculated; all kinematic and kinetic curves were normalised with respect to 100% of the gait cycle (GC) duration. In order to define the gait pattern of DMD subjects and to quantify their deviations from normality, some of the kinematic and kinetic indices proposed by Benedetti et al. [28] for both limbs were calculated. In particular, spatio-temporal parameters, joint angle values (for pelvis, hip, knee and ankle joints) at specific points of the GC and the maximum of hip and ankle power were analyzed. Stride length, step width and velocity were normalised with respect to the subjects’ height. Joint powers were normalised for body weight and are reported in W/kg. 2.3. Statistical analysis For each subject, each computed parameter was calculated as the mean of the values obtained in the three considered trials. Each trial was considered independent of the others. Mean values and standard deviations for the DMD and control group were computed thereafter. For some gait parameters (i.e. stance period, stride time, stride length, and all the kinematic parameters), an initial comparison between the right and left limb was made. No statistical difference was found between the two limbs, the data from both sides were pooled. Student’s t-test was used to estimate the effect of diagnosis (independent variable) on Gait Analysis parameters (dependent variables). Equality of variances was evaluated by Levene’s test [29]. Null hypotheses were rejected when nominal alpha 0.05. Results are expressed as mean standard deviation. The normality distribution was checked for all the variables using the Kolmogorov–Smirnov test.
37
Table 2 Means and standard deviations for manual muscular testing, graded according to the Medical Research Council’s scale Variables
NoT-DMD group
T-DMD group
Difference
Ileopsoas Rectus Femoris Gluteus Maximus Tibialis Anterior Gastrocnemius
3.65 .62 3.80 .34 3.86 .34 4.15 .35 4.68 .28
3.26 .71 3.90 .31 3.76 .39 3.91 .53 4.51 .40
– – – –
*
For the purpose of mean and standard deviation calculations, see the text, Section 2. * p-value < 0.05, calculated by comparison between NoT-DMD group and T-DMD group.
3. Results 3.1. Manual muscular testing An overall muscular weakness in DMD children (Table 2). The lowest MRC values were obtained for iliopsoas muscle, whereas the highest were obtained for gastrocnemius. The comparison between NoT-DMD group and T-DMD group showed iliopsoas muscles weaker (p < 0.05) in the untreated patients. 3.2. Gait Analysis Stride length values were significantly lower in DMD compared to healthy controls. Step width values were significantly higher compared to the control group (Table 3). No statistically significant differences in any spatio-temporal parameters were observed by the comparison of the treated DMD children and the untreated ones (Table 4). In Fig. 1 the mean kinematic and kinetic curves of the DMD group (in red) and of the control group (in blue) are shown. Only the most significant curves were presented. Anterior pelvic tilt in DMD was increased compared to the control group for the whole GC (p < 0.05 for mean pelvic tilt, Table 3) and a typical double bump pattern was evident. The hip was more flexed in terminal swing phase (85–100% of GC). Deviations at the knee were during loading response (0–10% of GC) and midstance (10–30% of GC). DMD patients did not achieve adequate knee flexion (p < 0.05 for max knee flexion in StP and p < 0.05 for min knee flexion in StP, Table 3); some of them had knee hyperextension (‘‘knee recurvatum’’, p < 0.05 for knee hyperextension, Table 3). The feet were in equinus position at initial contact (0– 5% of GC) (value at IC for ankle plantarflexion, Table 3) and the ankles remained excessively plantarflexed (p < 0.05 for maximal ankle plantarflexion in SwP, Table 3) during the swing phase (60–100% of GC). Excessive abduction in swing phase was observed at the hip level on frontal plane. The moment at knee was flexor in almost the whole stance phase of GC. The ankle moment demonstrated an abnormal pattern when compared with control group. Hip and ankle power were significantly reduced in DMD children in comparison to controls (p < 0.05 for max hip power and p < 0.05 for max ankle power, Table 3). No statistically significant differences in the kinematic pattern were observed between the two groups of DMD children (treated and untreated) (Table 4). However, the Not-T DMD-Group showed a statistically significant decrease of the ankle power (Table 4). 4. Discussion There were only previous studies assessing gait in muscular dystrophy. These involved small and not homogeneous groups [20–23].
M.G. D’Angelo et al. / Gait & Posture 29 (2009) 36–41
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Table 3 Means and standard deviations for spatio-temporal, kinematic and kinetic gait parameters in the whole group of DMD children (treated and untreated) and in healthy age/sex matched controls Variables
Parameter
Phase
DMD group
Control group
Difference
Stance time (% gait cycle) Cadence (steps/min) Velocity (m/(s H)) Stride length (m/H) Step width (m/H) Stride time (ms) Pelvic obliquity (8) Pelvic tilt (8) Pelvic rotation (8) Hip Ab-adduction (8) Hip rotation (8) Hip flex-extension (8) Hip flex-extension (8) Hip flex-extension (8) Knee flex-extension (8) Knee flex-extension (8) Knee flex-extension (8) Knee flex-extension (8) Knee flex-extension (8) Knee flex-extension (8) Knee Hyperextension (% gait cycle) Ankle plantar-flexion (8) Ankle plantar-flexion (8) Ankle plantar-flexion (8) Ankle plantar-flexion (8) Ankle plantar-flexion (8) Foot progression (8) H3 peak of hip power (W/kg) Maximum of ankle power (W/kg)
Value Value Value Value Value Value Mean Mean Mean Mean Mean Value Value Range Value Max Min Max Value Range Mean Value Max Max Value Range Mean Max Max
WCy WCy WCy WCy WCy WCy WCy WCy WCy WCy WCy IC TO WCy IC StP StP SwP TO WCy WCy IC StP SwP TO WCy WCy WCy WCy
57.4 2.0 132 20 0.81 0.14 0.737 0.053 0.093 0.021 935 169 5.0 2.3 14.6 5.0 7.9 3.2 2.9 3.3 2.1 8.6 33.7 5.5 3.5 6.9 48.1 5.6 7.7 5.9 9.3 6.7 0.9 5.8 60.6 8.1 37.2 9.4 62.2 6.0 15.7 14.5 4.6 6.6 10.6 6.6 5.0 7.7 16.1 8.7 26.8 6.9 14.5 7.9 0.449 0.471 1.899 0.745
57.2 2.0 131 11 0.90 0.13 0.818 0.067 0.062 0.010 922 71 3.6 1.3 10.0 3.8 5.9 1.8 1.6 2.9 3.9 6.3 33.4 3.8 2.0 4.2 47.0 3.8 8.9 4.8 16.1 5.0 2.9 4.9 59.6 5.4 40.3 6.7 58.2 3.4 4.9 6.5 .2 3.6 13.9 2.2 3.2 2.6 14.2 4.9 28.2 5.7 11.3 4.9 1.132 0.938 2.710 .779
– – – § §
– – §
– – – – – – – § §
– – § § § § §
– – – § §
Max: maximum; min: minimum; WCy: whole cycle; StP: stance phase; SwP: swing phase; IC: initial contact; TO: toe-off. Ab-adduction: abduction–adduction; Flexextension: flexion–extension. ‘–’: adimensional unit (stride length, step width normalised with respect to the subjects’ height). § p-value < 0.05, compared between DMD group (treated and untreated) and control group.
Table 4 Means and standard deviations for spatio-temporal, kinematic and kinetic gait parameters in the two different groups of DMD children (NoT-DMD and T-DMD group) Variables
Parameter
Phase
NoT-DMD group
T-DMD group
Difference
Stance time (% gait cycle) Cadence (steps/min) Velocity (m/(s H)) Stride length (m/H) Step width (m/H) Stride time (ms) Pelvic obliquity (8) Pelvic tilt (8) Pelvic rotation (8) Hip Ab-adduction (8) Hip rotation (8) Hip flex-extension (8) Hip flex-extension (8) Hip flex-extension (8) Knee flex-extension (8) Knee flex-extension (8) Knee flex-extension (8) Knee flex-extension (8) Knee flex-extension (8) Knee flex-extension (8) Knee Hyperextension (% gait cycle) Ankle plantar-flexion (8) Ankle plantar-flexion (8) Ankle plantar-flexion (8) Ankle plantar-flexion (8) Ankle plantar-flexion (8) Foot progression (8) H3 peak of hip power (W/kg) Maximum of ankle power (W/kg)
Value Value Value Value Value Value Mean Mean Mean Mean Mean Value Value Range Value Max Min Max Value Range Mean Value Max Max Value Range Mean Max Max
WCy WCy WCy WCy WCy WCy WCy WCy WCy WCy WCy IC TO AC IC StP StP SwP TO WCy WCy IC StP SwP TO WCy WCy WCy WCy
57.7 2.3 134 23 0.83 0.17 0.736 0.063 0.092 0.019 925 198 5.7 2.6 12.6 4.7 7.8 3.6 3.2 3.7 3.3 9.1 32.7 4.8 1.6 5.0 47.6 6.3 6.8 6.3 8.7 7.3 2.4 6.4 58.7 9.1 34.7 10.6 61.9 6.5 19.5 16.9 5.2 6.9 9.8 7.6 5.6 8.4 15.3 9.7 25.3 4.9 15.9 8.4 0.574 0.539 1.626 0.649
57.2 1.6 130 18 0.80 0.11 0.738 0.041 0.095 0.024 947 137 4.2 1.6 16.7 4.5 8.0 3.0 2.7 2.9 0.7 8.1 34.7 6.2 5.6 8.1 48.7 5.0 8.7 5.5 10.0 6.0 0.8 4.8 62.6 6.4 39.8 7.2 62.5 5.5 11.5 10.3 3.9 6.4 11.6 5.2 4.3 7.1 16.9 7.7 28.5 8.3 13.1 7.3 0.239 0.214 2.355 0.689
– – – – – – – – – – – – – – – – – – – – – – – – – – – – §
Max: maximum; min: minimum; WCy: whole cycle; StP: stance phase; SwP: swing phase; IC: initial contact; TO: toe-off; Ab-adduction: abduction–adduction; Flexextension: flexion–extension. ‘–’: adimensional unit (stride length, step width normalised with respect to the subjects’ height). § p-value < 0.05, compared between NoT-DMD group and T-DMD group.
M.G. D’Angelo et al. / Gait & Posture 29 (2009) 36–41
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Fig. 1. Mean kinematics and kinetics of DMD patients (red line) compared with control group (blue line) and with reference of literature (grey line with standard deviation). On the X-axis there is the percentage of gait cycle (0: heel strike, 100: the following ipsilateral heel strike) and on the Y-axis the unit from (A) to (E) is degrees, for (F) and (G) is N m/kg and for (H) and (I) is W/kg. Kinematic on sagittal plane: (A) pelvic tilt, (B) hip flexion–extension, (C) knee flexion–extension and (D) ankle dorsiflexion–plantarflexion. Kinematic on frontal plane: (E) hip abduction–adduction; kinetics on sagittal plane, (F) knee flexor–extensor moment, (G) ankle dorsiflexor–plantarflexor moment, (H) hip power and (I) ankle power. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of the article.)
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M.G. D’Angelo et al. / Gait & Posture 29 (2009) 36–41
In the present study a large, homogeneous group of children (with DMD), a similar age, muscle strength, weight and height was selected. We analyzed 21 DMD children; 10 of them were treated with steroids and 11 were not treated. The manual muscular test demonstrated that the weakest muscles were the most proximal ones as expected. An overall observation of gait patterns in DMD patients confirmed previously reported data [20–23]. The combination of gluteus maximus weakness and hip flexors’ tightness led to the presence of lumbar lordosis, an excessive anterior pelvic tilt and a ‘‘double bump’’ sagittal pelvic pattern. Quadriceps weakness affected the knee pattern in loading response, when patients avoided flexion of the knee. Knee hyperextension later in stance probably represented an attempt to maintain body stability while compensating for the weak quadriceps. This compensation was further demonstrated by the absence of extensor knee moment. Excessive foot plantarflexion during swing in DMD patients was compensated by increased flexion and abduction of the hip to aid clearance. Velocity and cadence in DMD patients was similar to those in healthy subjects. However stride length was reduced and step width was increased in order to improve balance. These gait characteristics were observed in DMD subjects aged around 7 years. Armand et al. [22] studied two DMD children, who were older (8 and 9.7 years) and more severely affected (mean MRC values were 3.1 + 0.7 and 2.5 + 0.7 in average) than those involved in the present study. The gait pattern of these two boys was more severely affected compared to the in respect to the present study: the ankle was plantarflexed in the whole gait cycle, knee hyperextension present in 0–40% of the gait cycle and the hip flexion in terminal swing was more evident. Considering the second analysis performed in the group of DMD patients, divided in to treated and untreated with steroids, the only statistically significant difference related to muscle strength evaluation between the two groups was found in the iliopsoas. On the other hand, the Gait Analysis parameters showed that only maximum ankle power was significantly higher in treated subjects compared to untreated ones. As demonstrated by several studies [5,8,10,11,15], steroids treatment does not alter significantly the natural history of the disease. Any positive effect of steroids on muscle strength is still a matter of discussion, despite their widely demonstrated effect on heart functioning and on scoliosis [8,11]. No previous studies analyzed the effects of steroids on gait pattern of Duchenne patients by using Gait Analysis. All previous therapeutic trials were limited in the methodology used to measure muscle strength, which was operator-dependent (e.g. the MRC) [5,10,15]. Manual muscle evaluation is operator dependent. External-temporal or spatial conditions can further influence the evaluation. In the present study both an operator dependent measure scale (i.e. MRC) and an instrumented and objective tool (i.e. Gait Analysis) were used. Comparison between treated and untreated Duchenne patients showed small differences for both the evaluations. Gait Analysis gives objective and quantitative information about the gait pattern of DMD subjects and the deviations due to muscular impairment. Since our study was a single time point evaluation, it presented the differences in the gait pattern of DMD children compared to sex and age matched controls. However, it was not possible in this context to unravel changes due to the progression of the disease or the treatment. Serial analysis during the time course of the disease as well as before and after the treatment should be performed.
Acknowledgments We would like to thank Maria Teresa Bassi for helpful suggestions; all the children and the families who participated to the work and the Fondazione Cariplo for supporting this project (HINT@LECCO).
Conflict of interest None.
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Gait & Posture journal homepage: www.elsevier.com/locate/gaitpost
Gait pattern in Duchenne muscular dystrophy Maria Grazia D’Angelo a,1,*, Matteo Berti a,1, Luigi Piccinini a, Marianna Romei a, Michela Guglieri a,b, Sara Bonato a, Alessandro Degrate a, Anna Carla Turconi a, Nereo Bresolin a,b a b
IRCCS E. Medea, NeuroRehabilitation Department, via don Luigi Monza 20, 23842 Bosisio Parini, Lecco, Italy Institute of Neuroscience, University of Milano, IRCCS Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, via F. Sforza 35, Milano, Italy
A R T I C L E I N F O
A B S T R A C T
Article history: Received 23 July 2007 Received in revised form 23 May 2008 Accepted 9 June 2008
We investigated the gait pattern of 21 patients with Duchenne muscular dystrophy (DMD), compared to 10 healthy controls through 3D Gait Analysis. An overall observation of gait pattern in our DMD patients when compared to controls confirmed the data previously reported for small dystrophic groups. An excessive anterior tilt of pelvis and abnormal knee pattern in loading response phase were found. Since during the swing phase the DMD foot is too plantarflexed, patients adopt a higher flexion and abduction of the hip in order to advance the swinging limb. Velocity and cadence of DMD patients resulted similar to those calculated for healthy subjects, whereas stride length was reduced and step width was increased. We then divided the DMD patients in to two subgroups (treated with steroids and untreated), and we observed that the only statistically significant differences between the two groups in Gait Analysis parameters were found for the maximum of ankle power. 3D Gait Analysis gives objective and quantitative information about the gait pattern and the deviations due to muscular situation of DMD subjects; being our study a single moment evaluation, it is otherwise unable to unravel changes only detectable through serial analysis during the time course of the disease and, if any, due to the treatment. ß 2008 Elsevier B.V. All rights reserved.
Keywords: Gait Analysis Duchenne muscular dystrophy Steroids treatment Ambulation Biomechanics
1. Introduction Duchenne muscular dystrophy (DMD) is the commonest childhood muscular dystrophy with a worldwide incidence of 1 in 3500 male live births. It is an X-linked recessive disorder, due to mutations in the dystrophin gene. Untreated, boys with DMD become progressively weak during their childhood and stop ambulation at a mean age of 9 years. Confinement to a wheelchair is followed by the development of scoliosis, respiratory failure and cardiomyopathy. Without intervention, the mean age at death is 19 years [1,2]; no curative treatment is known. Some studies have reported substantial long-term functional benefits from the steroid therapy: prolonged ambulation into the mid-teens, reduced severity of scoliosis, major preservation of respiratory and cardiac function [3–18] reflected by changes in weakness, which affects the proximal muscle groups first and the distal ones later, compromises the child’s posture and gait. A
* Corresponding author at: NeuroMuscular Unit, IRCCS E. Medea, NeuroRehabilitation Department, via don Luigi Monza 20, 23842 Bosisio Parini (Lecco) Italy, Tel.: +39 031 877870; fax: +39 031 877831. E-mail address: [email protected] (M.G. D’Angelo). 1 These authors equally contributed to the paper. 0966-6362/$ – see front matter ß 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.gaitpost.2008.06.002
dynamic quantitative assessment of gait in DMD patients would be important in evaluating the progression of the disease and the benefits of any therapy [19]. Few studies focused on gait of DMD children [20–23], sample sizes were small and/or not homogenous. The aim of the present study was the characterization of the gait pattern of a large group of DMD children at a single time point of their clinical history compared to healthy age and sex matched controls using three-dimensional Gait Analysis. 2. Materials and methods 2.1. Patients Twenty one DMD children were involved in this study; the diagnosis of DMD was established according to internationally accepted criteria [24]: progressive muscular weakness, increased muscle plasma enzymes, muscle biopsy identifying fiber degeneration and absence of the dystrophin protein, alterations in the dystrophin gene (deletions or other genetic alteration). Exclusion criteria included absence of additional conditions such as cerebral palsy, behavioural and/or psychiatric disturbances, acquired brain or spinal injuries, deafness, severe visual impairment, epilepsy and the ability to walk independently, without aids. Ten healthy children, age and sex matched, were recruited (all boys, mean age: 88.7 14.0 months). Patients and controls did not differ significantly in age, body weight and height (Table 1). Ten out of 21 DMD children began steroids treatment in other hospitals before coming to ours. Four children were under prednisone (0.75 mg/kg day) and six under deflazacort treatment (0.9 mg/kg day) [5,11,15]. Treatment was started at a
M.G. D’Angelo et al. / Gait & Posture 29 (2009) 36–41 Table 1 Means and standard deviations for demographic data Variables
Number of children Age (months) Height (cm) Body weight (kg)
NoT-DMD group
T-DMD group
Control group
11 79.4 33.2 117.5 13.6 22.6 7.8
10 88.0 23.2 120.7 11.6 25.6 9.1
10 88.7 14.0 127.3 7.0 25.0 4.3
Difference
– – –
p-value < .05, compared between NoT-DMD group (NoT: not Treated) and T-DMD group (T: treated).
mean age of 72 8.2 months. At the time of the evaluation the duration of treatment was ranging from 11 to 18 months. We divided the DMD patients in two subgroups: one—treated with steroids (T-DMD) and the other untreated (NoT-DMD) (see Table 1). A second analysis was performed in order to evaluate differences between treated and untreated patients. The mean chronological age of DMD children treated with steroids was 88.0 + 23.2 months and of the untreated ones was 79.4 + 33.2 months. 2.2. Methods The assessment included manual muscle test and three-dimensional Gait Analysis. Manual muscular testing was performed according to the Medical Research Council scale (MRC scale)[25]. Minimal differences in the clinical practice are indicated as ‘‘ ’’ or ‘‘+’’. For the purpose of mean and standard deviation calculations, a grade marked ‘‘ ’’ was considered to be the number of the grade minus 0.33, and a grade marked ‘‘+’’ was considered to be the number of the grade plus 0.33 (for example: 3 = 2.67) [22]. Parents of all children signed a written informed consent form, as approved by the Ethical Committee of our institution. The study was also approved by the Institute’s Human Ethics Committee according to the declaration of Helsinki. The Gait Analysis Laboratory is equipped with an 8-camera optoelectronic system (ELITE2002, BTS, Milan, Italy) working at a sampling rate of 100 Hz for kinematic movement evaluation [26], two force platforms (Kistler Instrument AG, Winterthur, Switzerland) for movement kinetics calculation, and a video recording system (BTS, Milan, Italy) synchronized with the optoelectronic system and force platforms. Markers (spherical retroflective markers: 15 mm in diameter) were positioned according to Davis’ protocol [27]. For data acquisition the subjects were asked to walk barefoot at their own natural pace (self-selected speed) along a walkway (8 m long, 1.5 m wide) where the two force platforms were placed. At least eight trials were collected for each subject in order to ensure the consistency of the data. In order to obtain kinetic data, subjects began their walking from a point, which allowed them to place one foot on the force plate without any modification of cadence or stride length. Only the trials in which the subjects correctly placed their feet on the platforms were considered for the analysis. For each subject, three trials were considered and the data related to left and right limbs were calculated; all kinematic and kinetic curves were normalised with respect to 100% of the gait cycle (GC) duration. In order to define the gait pattern of DMD subjects and to quantify their deviations from normality, some of the kinematic and kinetic indices proposed by Benedetti et al. [28] for both limbs were calculated. In particular, spatio-temporal parameters, joint angle values (for pelvis, hip, knee and ankle joints) at specific points of the GC and the maximum of hip and ankle power were analyzed. Stride length, step width and velocity were normalised with respect to the subjects’ height. Joint powers were normalised for body weight and are reported in W/kg. 2.3. Statistical analysis For each subject, each computed parameter was calculated as the mean of the values obtained in the three considered trials. Each trial was considered independent of the others. Mean values and standard deviations for the DMD and control group were computed thereafter. For some gait parameters (i.e. stance period, stride time, stride length, and all the kinematic parameters), an initial comparison between the right and left limb was made. No statistical difference was found between the two limbs, the data from both sides were pooled. Student’s t-test was used to estimate the effect of diagnosis (independent variable) on Gait Analysis parameters (dependent variables). Equality of variances was evaluated by Levene’s test [29]. Null hypotheses were rejected when nominal alpha 0.05. Results are expressed as mean standard deviation. The normality distribution was checked for all the variables using the Kolmogorov–Smirnov test.
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Table 2 Means and standard deviations for manual muscular testing, graded according to the Medical Research Council’s scale Variables
NoT-DMD group
T-DMD group
Difference
Ileopsoas Rectus Femoris Gluteus Maximus Tibialis Anterior Gastrocnemius
3.65 .62 3.80 .34 3.86 .34 4.15 .35 4.68 .28
3.26 .71 3.90 .31 3.76 .39 3.91 .53 4.51 .40
– – – –
*
For the purpose of mean and standard deviation calculations, see the text, Section 2. * p-value < 0.05, calculated by comparison between NoT-DMD group and T-DMD group.
3. Results 3.1. Manual muscular testing An overall muscular weakness in DMD children (Table 2). The lowest MRC values were obtained for iliopsoas muscle, whereas the highest were obtained for gastrocnemius. The comparison between NoT-DMD group and T-DMD group showed iliopsoas muscles weaker (p < 0.05) in the untreated patients. 3.2. Gait Analysis Stride length values were significantly lower in DMD compared to healthy controls. Step width values were significantly higher compared to the control group (Table 3). No statistically significant differences in any spatio-temporal parameters were observed by the comparison of the treated DMD children and the untreated ones (Table 4). In Fig. 1 the mean kinematic and kinetic curves of the DMD group (in red) and of the control group (in blue) are shown. Only the most significant curves were presented. Anterior pelvic tilt in DMD was increased compared to the control group for the whole GC (p < 0.05 for mean pelvic tilt, Table 3) and a typical double bump pattern was evident. The hip was more flexed in terminal swing phase (85–100% of GC). Deviations at the knee were during loading response (0–10% of GC) and midstance (10–30% of GC). DMD patients did not achieve adequate knee flexion (p < 0.05 for max knee flexion in StP and p < 0.05 for min knee flexion in StP, Table 3); some of them had knee hyperextension (‘‘knee recurvatum’’, p < 0.05 for knee hyperextension, Table 3). The feet were in equinus position at initial contact (0– 5% of GC) (value at IC for ankle plantarflexion, Table 3) and the ankles remained excessively plantarflexed (p < 0.05 for maximal ankle plantarflexion in SwP, Table 3) during the swing phase (60–100% of GC). Excessive abduction in swing phase was observed at the hip level on frontal plane. The moment at knee was flexor in almost the whole stance phase of GC. The ankle moment demonstrated an abnormal pattern when compared with control group. Hip and ankle power were significantly reduced in DMD children in comparison to controls (p < 0.05 for max hip power and p < 0.05 for max ankle power, Table 3). No statistically significant differences in the kinematic pattern were observed between the two groups of DMD children (treated and untreated) (Table 4). However, the Not-T DMD-Group showed a statistically significant decrease of the ankle power (Table 4). 4. Discussion There were only previous studies assessing gait in muscular dystrophy. These involved small and not homogeneous groups [20–23].
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Table 3 Means and standard deviations for spatio-temporal, kinematic and kinetic gait parameters in the whole group of DMD children (treated and untreated) and in healthy age/sex matched controls Variables
Parameter
Phase
DMD group
Control group
Difference
Stance time (% gait cycle) Cadence (steps/min) Velocity (m/(s H)) Stride length (m/H) Step width (m/H) Stride time (ms) Pelvic obliquity (8) Pelvic tilt (8) Pelvic rotation (8) Hip Ab-adduction (8) Hip rotation (8) Hip flex-extension (8) Hip flex-extension (8) Hip flex-extension (8) Knee flex-extension (8) Knee flex-extension (8) Knee flex-extension (8) Knee flex-extension (8) Knee flex-extension (8) Knee flex-extension (8) Knee Hyperextension (% gait cycle) Ankle plantar-flexion (8) Ankle plantar-flexion (8) Ankle plantar-flexion (8) Ankle plantar-flexion (8) Ankle plantar-flexion (8) Foot progression (8) H3 peak of hip power (W/kg) Maximum of ankle power (W/kg)
Value Value Value Value Value Value Mean Mean Mean Mean Mean Value Value Range Value Max Min Max Value Range Mean Value Max Max Value Range Mean Max Max
WCy WCy WCy WCy WCy WCy WCy WCy WCy WCy WCy IC TO WCy IC StP StP SwP TO WCy WCy IC StP SwP TO WCy WCy WCy WCy
57.4 2.0 132 20 0.81 0.14 0.737 0.053 0.093 0.021 935 169 5.0 2.3 14.6 5.0 7.9 3.2 2.9 3.3 2.1 8.6 33.7 5.5 3.5 6.9 48.1 5.6 7.7 5.9 9.3 6.7 0.9 5.8 60.6 8.1 37.2 9.4 62.2 6.0 15.7 14.5 4.6 6.6 10.6 6.6 5.0 7.7 16.1 8.7 26.8 6.9 14.5 7.9 0.449 0.471 1.899 0.745
57.2 2.0 131 11 0.90 0.13 0.818 0.067 0.062 0.010 922 71 3.6 1.3 10.0 3.8 5.9 1.8 1.6 2.9 3.9 6.3 33.4 3.8 2.0 4.2 47.0 3.8 8.9 4.8 16.1 5.0 2.9 4.9 59.6 5.4 40.3 6.7 58.2 3.4 4.9 6.5 .2 3.6 13.9 2.2 3.2 2.6 14.2 4.9 28.2 5.7 11.3 4.9 1.132 0.938 2.710 .779
– – – § §
– – §
– – – – – – – § §
– – § § § § §
– – – § §
Max: maximum; min: minimum; WCy: whole cycle; StP: stance phase; SwP: swing phase; IC: initial contact; TO: toe-off. Ab-adduction: abduction–adduction; Flexextension: flexion–extension. ‘–’: adimensional unit (stride length, step width normalised with respect to the subjects’ height). § p-value < 0.05, compared between DMD group (treated and untreated) and control group.
Table 4 Means and standard deviations for spatio-temporal, kinematic and kinetic gait parameters in the two different groups of DMD children (NoT-DMD and T-DMD group) Variables
Parameter
Phase
NoT-DMD group
T-DMD group
Difference
Stance time (% gait cycle) Cadence (steps/min) Velocity (m/(s H)) Stride length (m/H) Step width (m/H) Stride time (ms) Pelvic obliquity (8) Pelvic tilt (8) Pelvic rotation (8) Hip Ab-adduction (8) Hip rotation (8) Hip flex-extension (8) Hip flex-extension (8) Hip flex-extension (8) Knee flex-extension (8) Knee flex-extension (8) Knee flex-extension (8) Knee flex-extension (8) Knee flex-extension (8) Knee flex-extension (8) Knee Hyperextension (% gait cycle) Ankle plantar-flexion (8) Ankle plantar-flexion (8) Ankle plantar-flexion (8) Ankle plantar-flexion (8) Ankle plantar-flexion (8) Foot progression (8) H3 peak of hip power (W/kg) Maximum of ankle power (W/kg)
Value Value Value Value Value Value Mean Mean Mean Mean Mean Value Value Range Value Max Min Max Value Range Mean Value Max Max Value Range Mean Max Max
WCy WCy WCy WCy WCy WCy WCy WCy WCy WCy WCy IC TO AC IC StP StP SwP TO WCy WCy IC StP SwP TO WCy WCy WCy WCy
57.7 2.3 134 23 0.83 0.17 0.736 0.063 0.092 0.019 925 198 5.7 2.6 12.6 4.7 7.8 3.6 3.2 3.7 3.3 9.1 32.7 4.8 1.6 5.0 47.6 6.3 6.8 6.3 8.7 7.3 2.4 6.4 58.7 9.1 34.7 10.6 61.9 6.5 19.5 16.9 5.2 6.9 9.8 7.6 5.6 8.4 15.3 9.7 25.3 4.9 15.9 8.4 0.574 0.539 1.626 0.649
57.2 1.6 130 18 0.80 0.11 0.738 0.041 0.095 0.024 947 137 4.2 1.6 16.7 4.5 8.0 3.0 2.7 2.9 0.7 8.1 34.7 6.2 5.6 8.1 48.7 5.0 8.7 5.5 10.0 6.0 0.8 4.8 62.6 6.4 39.8 7.2 62.5 5.5 11.5 10.3 3.9 6.4 11.6 5.2 4.3 7.1 16.9 7.7 28.5 8.3 13.1 7.3 0.239 0.214 2.355 0.689
– – – – – – – – – – – – – – – – – – – – – – – – – – – – §
Max: maximum; min: minimum; WCy: whole cycle; StP: stance phase; SwP: swing phase; IC: initial contact; TO: toe-off; Ab-adduction: abduction–adduction; Flexextension: flexion–extension. ‘–’: adimensional unit (stride length, step width normalised with respect to the subjects’ height). § p-value < 0.05, compared between NoT-DMD group and T-DMD group.
M.G. D’Angelo et al. / Gait & Posture 29 (2009) 36–41
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Fig. 1. Mean kinematics and kinetics of DMD patients (red line) compared with control group (blue line) and with reference of literature (grey line with standard deviation). On the X-axis there is the percentage of gait cycle (0: heel strike, 100: the following ipsilateral heel strike) and on the Y-axis the unit from (A) to (E) is degrees, for (F) and (G) is N m/kg and for (H) and (I) is W/kg. Kinematic on sagittal plane: (A) pelvic tilt, (B) hip flexion–extension, (C) knee flexion–extension and (D) ankle dorsiflexion–plantarflexion. Kinematic on frontal plane: (E) hip abduction–adduction; kinetics on sagittal plane, (F) knee flexor–extensor moment, (G) ankle dorsiflexor–plantarflexor moment, (H) hip power and (I) ankle power. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of the article.)
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M.G. D’Angelo et al. / Gait & Posture 29 (2009) 36–41
In the present study a large, homogeneous group of children (with DMD), a similar age, muscle strength, weight and height was selected. We analyzed 21 DMD children; 10 of them were treated with steroids and 11 were not treated. The manual muscular test demonstrated that the weakest muscles were the most proximal ones as expected. An overall observation of gait patterns in DMD patients confirmed previously reported data [20–23]. The combination of gluteus maximus weakness and hip flexors’ tightness led to the presence of lumbar lordosis, an excessive anterior pelvic tilt and a ‘‘double bump’’ sagittal pelvic pattern. Quadriceps weakness affected the knee pattern in loading response, when patients avoided flexion of the knee. Knee hyperextension later in stance probably represented an attempt to maintain body stability while compensating for the weak quadriceps. This compensation was further demonstrated by the absence of extensor knee moment. Excessive foot plantarflexion during swing in DMD patients was compensated by increased flexion and abduction of the hip to aid clearance. Velocity and cadence in DMD patients was similar to those in healthy subjects. However stride length was reduced and step width was increased in order to improve balance. These gait characteristics were observed in DMD subjects aged around 7 years. Armand et al. [22] studied two DMD children, who were older (8 and 9.7 years) and more severely affected (mean MRC values were 3.1 + 0.7 and 2.5 + 0.7 in average) than those involved in the present study. The gait pattern of these two boys was more severely affected compared to the in respect to the present study: the ankle was plantarflexed in the whole gait cycle, knee hyperextension present in 0–40% of the gait cycle and the hip flexion in terminal swing was more evident. Considering the second analysis performed in the group of DMD patients, divided in to treated and untreated with steroids, the only statistically significant difference related to muscle strength evaluation between the two groups was found in the iliopsoas. On the other hand, the Gait Analysis parameters showed that only maximum ankle power was significantly higher in treated subjects compared to untreated ones. As demonstrated by several studies [5,8,10,11,15], steroids treatment does not alter significantly the natural history of the disease. Any positive effect of steroids on muscle strength is still a matter of discussion, despite their widely demonstrated effect on heart functioning and on scoliosis [8,11]. No previous studies analyzed the effects of steroids on gait pattern of Duchenne patients by using Gait Analysis. All previous therapeutic trials were limited in the methodology used to measure muscle strength, which was operator-dependent (e.g. the MRC) [5,10,15]. Manual muscle evaluation is operator dependent. External-temporal or spatial conditions can further influence the evaluation. In the present study both an operator dependent measure scale (i.e. MRC) and an instrumented and objective tool (i.e. Gait Analysis) were used. Comparison between treated and untreated Duchenne patients showed small differences for both the evaluations. Gait Analysis gives objective and quantitative information about the gait pattern of DMD subjects and the deviations due to muscular impairment. Since our study was a single time point evaluation, it presented the differences in the gait pattern of DMD children compared to sex and age matched controls. However, it was not possible in this context to unravel changes due to the progression of the disease or the treatment. Serial analysis during the time course of the disease as well as before and after the treatment should be performed.
Acknowledgments We would like to thank Maria Teresa Bassi for helpful suggestions; all the children and the families who participated to the work and the Fondazione Cariplo for supporting this project (HINT@LECCO).
Conflict of interest None.
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