multiple sclerosis ( ms ) is a neurologic disease affecting an estimated 2.5 million adults worldwide and is the most common disabling neurological disease in young adults .
ms is diagnosed between ages 20 and 50 , is 2 to 3 times more common in women than in men , and results in demyelination and axonal loss in the central nervous system ( cns ) .
such cns damage may result in ambulatory limitations which are key components of disability in patients with ms .
approximately 75% of these patients experience clinically significant walking and balance disturbances   which may present even in the early stages of the disease and in individuals diagnosed with clinically isolated syndrome .  
gait impairments are associated with the severity of deficiency in various functional neurological systems , that is , muscle power loss , level of spasticity , degree of instability due to impaired coordination , and degree of sensory impairment . impairment in one functional system alone or in combination contributes to the patient 's gait impairment , resulting in a specific gait pattern .
therefore , increasing awareness of walking and balance limitations in this patient group requires continuous evaluation .
assessment is essential in order to monitor disease dynamics and assess the efficacy of symptomatic and rehabilitation therapies .   
assessment of gait performance in people with ms consists of clinician - assessed rating scales , performance tests , and self - reporting questionnaires . with the advent of modern instrumented walkway systems ,
basic spatiotemporal gait parameters have been increasingly used by clinicians to define the characteristics of pathological gait due to ms and to assess interventions aimed at improving gait .
it is widely accepted that people with ms walk at a slower speed , extend the period of time when both legs contact the ground , and have a wider base of support compared to healthy subjects [ 9 , 10 ] . moreover , givon et al .
( 2009 ) demonstrated significant correlations between various spatiotemporal gait parameters with the level of neurological impairment due to ms .    on the other hand , length restrictions of commercial instrumented walkways
moreover , since the standard electronic walkways analyze only a small number of steps , it may not reflect the impact of fatigue on gait performance .  
recently , treadmill gait analysis has been proposed as an attractive alternative for overground walking measuring systems .
the instrumented treadmill enables collection of gait performance over long distances and/or long periods of time using standardized conditions , namely , distance , belt speed , and inclination .
treadmills require less space and in specific models , can be safely operated due to the overhanging harness which is equipped with an emergency belt stop option if the subject / patient trips or collapses .   
although instrumented treadmills have generated outcome measures relating to acquired brain injury , no study to date has evaluated gait with instrumented treadmills in people with ms .
therefore , the purpose of this study was twofold : first to determine spatiotemporal parameters of treadmill gait in patients with ms and second to examine whether these parameters are associated with specific functional impairments in this cohort .
eighty - seven relapsing - remitting patients diagnosed with ms , 50 women and 37 men , aged 40.9  11.9  , were recruited from the multiple sclerosis center , the sheba medical center , tel - hashomer , israel , and participated in this investigation .
inclusion criteria included ( 1 ) a neurologist - confirmed diagnosis of definite relapsing - remitting ms according to the revised mcdonald criteria ; ( 2 ) less than 6 on the expanded disability status scale ( edss ) , equivalent to walking without an assistive device ( e.g. , a cane or walker ) ; and ( 3 ) relapse - free for at least 30 days prior to testing . exclusion criteria included ( 1 ) orthopedic disorders that could negatively affect mobility ; ( 2 ) major depression or cognitive decline ; ( 3 ) pregnancy ; ( 4 ) blurred vision ; and ( 5 ) cardiovascular disorders .
twenty - five apparently healthy subjects , 14 women and 11 men , aged 38.5  9.4 , served as controls .
gait spatiotemporal parameters were obtained using the zebris fdm - t treadmill ( zebris medical gmbh , germany ) .
the zebris fdm - t is fitted with an electronic mat of 10,240 miniature force sensors , each approximately 0.85  0.85  cm embedded underneath the belt .
the treadmill 's contact surface measures 150  50  cm and its speed can be adjusted from 0.2 to 22  km / h , at intervals of 0.1  km / h .
when the subject stands / walks on the treadmill , the force exerted by his feet ( the so - called reactive - normal force ) is recorded by the sensors at a sampling rate of 120  hz . due to the high density of the sensors ,
the foot is mapped at a high resolution to facilitate even subtle changes in force distribution .
dedicated software integrates the force signals and provides 2d/3d graphic representation of major spatiotemporal parameters including center of pressure ( cop ) trajectories during static stance and gait .  
( 2012 ) reported high levels of between- and within - day reliability in healthy seniors for the majority of spatiotemporal gait parameters recorded by the zebris treadmill system during walking , with coefficients of variation typically below 5% and 7% , respectively .
the dedicated software also generates a graphic pattern termed the  butterfly  , representing a continuous trace of the cop trajectory during walking ( figure 1 ) .   
the following set of parameters was derived from the butterfly.anterior/posterior variability ( mm ) : defined as the standard deviation of the intersection point in the anterior / posterior direction.lateral symmetry ( mm ) : left / right shift of the intersection point ;  zero position 
is equivalent to perfect symmetry.lateral variability ( mm ) : defined as the standard deviation of the lateral symmetry .  
anterior / posterior variability ( mm ) : defined as the standard deviation of the intersection point in the anterior / posterior direction . lateral symmetry ( mm ) : left / right shift of the intersection point ;  zero position 
lateral variability ( mm ) : defined as the standard deviation of the lateral symmetry .   
prior to the measurement phase , all participants actively participated in an adaptation - familiarization trial in order to establish each individual 's speed level .
starting at a fixed speed of 0.5  km / h , the belt speed was increased by 0.3  km / h every 15 seconds in a stepwise manner . once the participant informed the tester that speed that best characterized his / her normal walking pace
was determined as his / her comfort speed , following this adaptation phase , each participant was instructed to walk without shoes on the treadmill for one consecutive minute at the comfort speed .  
group differences in age and gender distribution were determined using an independent sample t - test and chi - square test , respectively .
differences in average and variability of gait parameters between individuals with ms and controls were determined using an independent sample t - test .
the magnitudes of group differences were indexed by a 95% confidence interval ( 95% ci ) .
spearman 's rank correlation coefficient was used to examine the association between spatiotemporal gait parameters and level of neurological impairment defined by the edss .
the patient group had a mean duration of 6.0  6.2 years since diagnosis and an edss score of 2.7  1.6 , representing moderate neurological disability .
the mean pyramidal , cerebellar , and sensory scores were 1.6  1.2 , 1.0  1.1 , and 0.8  1.0 , respectively .
significant differences were observed between patients and healthy subjects with respect to all 14 parameters .
people with ms demonstrated shorter steps , extended stride time , and a wider base of support compared to the healthy controls .
patients walked with a longer step time , reduced single support phase , and a longer period of time with both legs on the treadmill 's belt ( double support ) .
it is worth noting that although both groups were instructed to increase the treadmill speed to comfort level , the patients ' self - selected velocity was 59% slower than their healthy counterparts ( 2.2 versus 3.5  km / h , p < 0.001 ) .    with respect to the butterfly diagram , significant differences between groups were observed in the lateral symmetry , anterior - posterior variability , and lateral variability parameters .
patients scored on average 2.5 times higher in all three parameters compared to the healthy participants .   
the strongest correlation was with the double support parameter ( spearman 's rho = 0.65 ) .
moderate associations were found during the single support period and stance phase : rho 0.61 , 0.61 ( spearman 's rho ) , respectively .
the least correlated were step , stride time and width of support : 0.28 , 0.31 , 0.35   ( rho ) , respectively .  
positive correlations were observed between the edss score and parameters derived from the butterfly diagram .
of the three parameters , the anterior - posterior and lateral variability parameters revealed the strongest correlations : spearman 's rho = 0.55 , 0.56  ( rho ) , respectively .
the correlation scores between spatiotemporal gait parameters and the neurological variables are outlined in table 3 .
our primary aim was to examine if spatiotemporal parameters derived from an instrumented treadmill ( zebris medical gmbh ) could distinguish between people with ms and age , gender , height and weight matched controls .
main spatiotemporal gait features demonstrated by people with ms were a slower self - selected speed , shorter step and stride length , wider base of support and a prolonged double support phase , compared to the healthy participants .
our findings are consistent with those previously presented in relatively large groups of ms patients , however , performed on an electronic walkway [ 9 , 10 ] . since treadmill gait analysis is a relatively new measurement device for gait analysis in people with ms , it is worth discussing the difference between the current study gait instrument to conventional over ground gait measurement tools .    walking on an instrumented treadmill , used in this study ,
specifically , compared to the gaitrite electronic walkway , treadmill gait analysis is not limited to the number of steps per trial .
we assume that this ability is essential in the ms population due to fatigue concerns .
recently , energy cost of walking was significantly and inversely associated with gait speed ( r = .25 ) and stride length ( r = .32 ) and positively associated with double limb support ( r = .27 ) in people with mild ms .
secondly , with an instrumented treadmill the individual is able to control the speed , allowing for more standardized testing of gait characteristics including the high end of gait jogging .
thirdly , this innovative device enables gait measurement while walking on an inclined surface , a condition that may correspond to several active daily situations ( e.g. , walking up hill or on sloped roads ) .
furthermore , we believe that the instrumented treadmill is better fitted for measuring gait performance in studies involving an intervention program based on treadmill training , body weight treadmill training and robot - assisted treadmill training .    on the other hand , treadmill gait analysis poses other problems as it may impede natural walking patterns .
energy costs have been reported to be higher during treadmill walking than ground walking   while kinematic parameters during both tasks are inconsistent [ 15 , 16 ] .
moreover , evidence suggests that due to the automatic and regular drive to the lower limbs , kinesthetic and external afferent impulses may differ between ( both ) tasks which may affect the generation of locomotor patterns .
these aspects should be taken into consideration when interpreting treadmill gait findings and implementation of observed gait deviations in intervention strategies .    according to these statements
, we believe that the relatively slow - selected speed , decreased step length , and prolonged double support demonstrated by the current patient group were associated with the afferent impulse derived by the treadmill .
normal performance of walking on a treadmill is characterized by a positive correlation between belt speed to step length and pace of steps .
that is to say , that if the walking subject fails to increase at least one of these two spatiotemporal variables , as a response to an increase in speed , he is at risk of falling .
we assume that , despite the adaptation - familiarization trial , people with ms still felt a lack of confidence while walking on the treadmill .
high concerns about falls have been shown to be primarily associated with decreased step lengths in elderly females .
we assumed that in order to avoid extended step lengths , people with ms preferred to reduce the treadmill 's speed . as a result of the slow speed ,
short step lengths were maintained and consequently the double support phase increased , which added to balance control .
puh and baer 's study performed on independently ambulatory stroke patients , supports our assumption .
stroke patients demonstrated a significantly slower velocity and longer double support phase in treadmill walking compared to over ground walking . despite our speculation ,
future studies focusing on spatiotemporal adaptations in accordance with different speed levels in people with ms are required .   
this diagram , which in a healthy subject resembles a papillion tie , provides us with information as to the level of symmetry between steps , width of base of support , single and double support phases , and the regularity with which gait is conducted .    in the current study
, people with ms demonstrated a greater variability in both the sagittal and coronal planes and asymmetrical cop movement pattern .
interestingly , with the exception of width between steps , these parameters were correlated with the level of neurological disability , for example , the edss and the pyramidal and cerebellar functional domains indicated by spearman 's rho ranging 0.550.65 .
our results are in line with other reports documenting increased variability of spatiotemporal gait parameters in individuals with ms compared to healthy controls [ 10 , 19 , 20 ] .
gait variability has been shown to have clinical import in other special populations , that is , parkinson , alzheimers , and so forth and is also associated with falls in the elderly .
one investigation   demonstrated that recurrent fallers with ms ( i.e. , 1 falls / year ) exhibit greater variability of spatial footfall placement than nonfallers with ms . nevertheless , following our analysis , indicating a correlation between variability of cop movement with the edss score , we tend to consider gait variability as a relevant marker of mobility deficits in ms .   
although persons with ms are clearly characterized with gait impairments , the mechanisms underlying this condition remain unclear . in this regard treadmill
gait analysis as performed in the present study had no known added value compared to over ground gait analysis . based on the belief that gait control involves numerous neural processes and coordination of the trunk and limbs , it is most likely not a single mechanism , but rather a combination of deficits that contribute to a general abnormal gait pattern .
possible factors such as decreased muscle strength , spasticity , fatigue , ataxic movement disorders , proprioception , and balance impairments   are often cited as contributing mechanisms .
there is also some evidence that attention resources are related to gait deficits in persons with ms .  
future studies should take advantage of the instrumented treadmill 's specific capabilities , that is , examining gait and balance performance over long distances , information that can potentially improve today 's knowledge regarding the impact of fatigue over mobility .
additionally , measurement of walking determinants , while walking on sloped surfaces , can be relevant for minimally impaired ms patients
. moreover , spatiotemporal analysis of high - demanding activities such as jogging or running can be monitored by this device . finally , a comparison of kinematic and kinetic parameters between treadmills to over ground walking in the ms population is warranted .
our results indicate that the instrumented treadmill is an appropriate tool for assessing ambulation capabilities of people with ms .
furthermore , spatiotemporal gait parameters collected by this device seem to be valid markers of neurological impairment in the ms population .
further study is indicated especially regarding the comparative sensitivity of the treadmill outcome parameters in capturing changes in gait function .
 
 background and objective . treadmill gait analysis has been proposed as an attractive alternative for overground walking measuring systems . 
 the purpose of this study was twofold : first to determine spatiotemporal parameters of treadmill gait in patients with multiple sclerosis ( ms ) and second to examine whether these parameters are associated with specific functional impairments in this cohort . 
 method . 
 eighty - seven relapsing - remitting patients diagnosed with ms , 50 women and 37 men , aged 40.9  11.9 with an expanded disability status scale ( edss ) score of 2.7  1.6 , participated in this study . 
 twenty - five apparently healthy subjects , 14 women and 11 men , aged 38.5  9.4 , served as controls . 
 spatiotemporal gait parameters were obtained using the zebris fdm - t treadmill ( zebris medical gmbh , germany ) . 
 people with ms demonstrated significantly shorter steps , extended stride time , wider base of support , longer step time , reduced single support phase , and a prolonged double support phase compared to the healthy controls . the edss score was significantly correlated with all spatiotemporal gait parameters . 
 conclusion . 
 the instrumented treadmill may be an effective tool in assessing ambulation capabilities of people with ms . 
1. Introduction
2. Methods 
3. Results
4. Discussion
5. Conclusion