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Walking for six minutes increases both simple reaction time and stepping reaction time in moderately disabled people with Multiple Sclerosis

Multiple Sclerosis and Related Disorders



Walking ability and fatigue are often reported as the most disabling symptoms in Multiple Sclerosis (MS). Motor fatigue may contribute to reduced mobility, and is likely caused by both central and peripheral deterioration in neuromuscular function. Simple and choice stepping reaction time (RT) measures have the potential to detect walking induced changes in motor impairment.


The aim of this study was to assess the effect of six minutes of walking on simple and choice stepping RT in people with MS.


31 people with moderate walking disability and a diagnosis of MS completed simple and choice stepping RT tasks, and rated their levels of fatigue on a 100 mm visual analogue scale before and after a modified six minute walk test.


Subjects walked an average of 368(±110)m in six minutes. Perceived fatigue increased following the six minute walk, as indicated by a 25(±19.7)mm increase on the 100 mm visual analogue scale (p<0.001). There was a significant increase in both hand (p=0.003) and foot (p=0.006) simple RT following the six minute walk. For choice stepping RT, response time was significantly slower (p=0.006) following the six minute walk, while movement time was unchanged (p=0.506).


Simple and choice stepping reaction times are slower following six minutes of walking in people with MS. These findings suggest that walking-induced fatigue might lead to central slowing and slowed stepping performance. Further studies are needed to investigate the clinical relevance of these RT measures in relation to fall risk and therapeutic interventions to improve mobility and manage fatigue in people with MS.



  • Six minutes of walking induces fatigue in MS.
  • Walking induced fatigue increases hand and foot RT, and stepping RT.
  • Increased hand RT may be indicative of a central mechanism of fatigue.

Abbreviations: MS - Multiple Sclerosis, RT - Reaction Time, EDSS - Expanded Disability Status Scale, FSS - Fatigue Severity Scale.

Keywords: Multiple Sclerosis, Reaction Time, Fatigue, Walking, Motor Skills, Visual Motor Co-ordination.

1. Introduction

Walking ability ( Johansson et al., 2007 ) and fatigue (Bakshi, 2003 and Schwid et al, 2002) are often reported as the most disabling impairments by people with Multiple Sclerosis (MS). A multidisciplinary consensus conference in 2007 by the Consortium of Multiple Sclerosis Centres recommended that a global outcome measure for fatigue be developed that would include an examination of fatigue throughout the MS disease course and be quick and easy to administer ( Hutchinson et al., 2009 ). There is a known difficulty in measuring motor fatigue, and a physiological approach is needed to detect motor impairments. Activity dependent motor fatigue has been measured in previous studies using maximum voluntary contraction ( Schwid et al., 1999 ). Neurophysiological studies suggest that motor fatigue is likely to be caused by both central and peripheral deterioration in neuromuscular function and is associated with reduced walking speed and cadence ( Ng et al., 2004 ). Kinetic gait parameters have also shown some associations with perceived fatigue levels ( Huisinga et al., 2011 ) however these laboratory measures are beyond the scope of normal clinical practice.

Reaction Time (RT) measures have the potential to detect important fatigue-related motor impairments in a clinical setting. RT is slower in people with MS compared with healthy controls ( Bailey et al., 2007 ), and has previously been shown to further deteriorate with mental fatigue ( Jennekens-Schinkel et al., 1988 ). Recently, Claros-Salinas et al. (2013) used a RT task as a measure of alertness in people with MS and healthy controls before and after both cognitive and physical exertion. They showed that hand RT was slower in people with MS compared with healthy controls, and worsened with cognitive fatigue and walking-induced fatigue. It is unclear how far or long participants walked to induce physical fatigue. Another study has shown that walking for an average duration of six minutes increases perceived fatigue in people with MS ( Crenshaw et al., 2006 ), but does not elicit an increase in kinematic or kinetic variability in people with minimal disability. In people with MS, more cognitively challenging walking tasks result in larger variations in spatiotemporal parameters of gait ( Hamilton et al., 2009 ). Even in people with MS with mild disability and no pyramidal signs, the double support phase of gait is prolonged compared with healthy controls ( Martin et al., 2006 ), which may indicate a delayed stepping time when walking.

Impaired choice stepping RT has been shown to be a significant predictor of falls in people with MS ( Hoang et al., in press ) and older people ( Lord and Fitzpatrick 2001 ). In a prospective study of falls in people with moderate MS (EDSS 3.5–6.0), Nilsagard et al. (2009) have also reported that an increased time taken to complete the Four Square Step Test was significantly associated with an increased risk of falls. Reicker et al. (2007) demonstrated that choice hand RT in people with MS is slower compared to both simple RT and choice RT in healthy controls, and suggest that a combination of motor dysfunction and changes in cognitive processing influences the performance of people with MS. The functional significance of these results and the influence of fatigue on RT in people with MS have not been reported.

Most existing literature has reported the effect of strenuous muscle activity on fatigability, as opposed to the fatigue that accompanies routine daily activities such as walking ( Dobkin, 2008 ). Measures of simple and choice RT have the potential to assess important fatigue related motor impairments that are important for walking and fall prevention. The aim of this study was to investigate the effects of walking on simple RT and choice stepping RT in people with MS. We hypothesised that walking for six minutes would induce fatigue and have a detrimental effect on simple and choice RT.

2. Methods

2.1. Participants

Thirty-one people (23 women and 8 men) with a diagnosis of MS were recruited from the MS Society of South Australia, the MS Rehabilitation Clinic at the Repatriation General Hospital and from private physiotherapy clinics in South Australia. Inclusion criteria were an Expanded Disability Status Scale (EDSS) ( Kurtzke, 1983 ) score of 3.0–6.0 and being able to walk for six minutes with or without the aid of a walking stick. Exclusion criteria included exacerbation or relapse of MS within the last 3 months, use of medication prescribed for fatigue or mobility, and having arthritis or other illness that severely limits walking. All participants provided written informed consent and ethical approval was granted by the Repatriation General Hospital Research and Ethics Committee (EC00191). This investigation was part of a larger study examining fatigue and walking ability in MS ( McLoughlin et al., 2012 ).

2.2. Fatigue protocol

To induce fatigue, participants repeatedly walked back and forth along a marked 10 m section of a 20 m hall, following the instructions “walk as far as you can in six minutes, bearing in mind that you need to last for six minutes”. The six minute walk, aimed at maximising effort, has previously been used to assess motor fatigue in people with MS ( Goldman et al., 2008 ).

2.3. Pre- and post-fatigue assessment

Participants rated their level of fatigue and underwent tests of simple and choice stepping RT before and after the six minute walk test. Participants rated their fatigue using a visual analogue scale – a 100 mm line with end descriptors of “not at all” and “very severe” ( Lee et al., 1991 ).

2.3.1. Simple Reaction Time

Simple RT was assessed in milliseconds using a hand-held electronic timer with a light as the stimulus and depression of a switch by the finger or the foot as the response ( Lord, et al., 2003 ). The hand RT task utilised a modified computer mouse, held in the dominant hand, and required an index finger press as the response. The foot RT test was conducted on the most affected side (the side with unilateral drop foot), using a foot pedal switch. Five practice trials were undertaken for both hand and foot RT tests, followed by 10 experimental trials, for which results were recorded and averaged.

2.3.2. Choice stepping Reaction Time

A custom made device incorporating a step mat interfaced with a standard PC was used to measure choice stepping RT ( Fig. 1 ). The mat was placed on the floor in front of the computer screen that displayed a graphical representation of the step mat (two centre pads, two side pads, and two front pads). Arrows representing the two side and front pads were illuminated on the screen (stimulus) as a cue to initiate stepping onto the corresponding pad (response). Participants stood on the two centre pads, and were instructed to step as quickly as possible onto the cued pad following stimulus presentation. After a practice trial of each directional pad, a total of 20 experimental trials (4 pads×5 trials) were presented in a random computer-generated order. Time taken from the stimulus presentation to foot lift from the centre pad (response time) and time from foot lift to step on the target pad (movement time) were computed and subsequently averaged for each participant.


Fig. 1 Choice stepping reaction time mat with an on-screen representation of the pads.

2.4. Statistical analysis

Data were initially checked for skewness and kurtosis. A repeated measure multiple analysis of variance was used to examine differences between the pre- and post-six minute walk measurements. Univariate analyses were then performed to assess which of the RT measures demonstrated significant differences. Data were analysed using SPSS version 19 (Chicago, IL, USA) with the level of statistical significance set atp<0.05. Despite the multiple comparisons made,Pvalues were not adjusted in this exploratory study as such adjustments may increase Type II errors, especially in studies with small sample sizes ( Perneger, 1998 ).

3. Results

Table 1 presents results for participant age, EDSS, fatigue severity, walking distance, and perceived fatigue measures. Participants had moderate severity MS, as indicated by their EDSS scores and reported a moderate level of fatigue. Fifteen of the 31 participants (48.4%) were classified as having fatiguing MS. All participants completed six minutes of walking with an average distance walked of 368 m (±110). Perceived fatigue increased following the 6 min walk, as indicated by a 25(±19.7)mm increase on the visual analogue scale (p<0.001).

Table 1 Participant age, disability, walking distance, self-reported fatigue and perceived fatigue measures.

  Mean (SD) Range
Age (years) 49 (10) 28–71
EDSS 3.7 (0.7) 3–6
FSS 4.7 (1.8) 1–7
6MWT distance (m) 368 (110) 160–612
VAS-F pre (mm) 18 (22.4) 0–76
VAS-F post (mm) 43 (31.6) 0–93

EDSS=Expanded Disability Status Scale; FSS=Fatigue Severity Scale; 6MWT=six-minute walk test; VAS-F=Visual Analogue Scale for Fatigue.

Simple and choice stepping RT test results are presented in Table 2 . The multiple analysis of variance revealed a significant time effect (F1,30=12.33,p=0.001) indicating an overall slowing of RT post six-minute walk. The univariate comparisons revealed significant increases in hand and foot simple RT and choice stepping RT response time following the six minute walk. In contrast, choice stepping RT movement time was unchanged.

Table 2 Simple and choice stepping reaction time measures before and after the six minute walk.

Measure Pre-walk mean (SD) Post-walk mean (SD) p
Simple hand RT (ms) 249 (43) 262 (43) 0.006
Simple foot RT (ms) 344 (47) 369 (50) 0.003
Choice stepping RT response (ms) 832 (100) 860 (104) 0.006
Choice stepping RT movement (ms) 331 (69) 323 (85) 0.506

RT=Reaction Time. All measures in milliseconds (ms).

4. Discussion

Our results show that six minutes of walking increases perceived fatigue and leads to slower RT for people with MS. The decline in simple hand and foot RT demonstrates that walking has a global effect on central aspects of motor control. Additionally, the reduction in choice stepping RT demonstrates the associated functional implications of this impairment on stepping ability.

Previous studies have shown a link between fatigue in MS and RT, indicating a fatigue-related motor impairment. Andreasen et al. (2010) demonstrated that cognitive processing speed is slower in people with MS than controls, and that people with MS who also report fatigue have slower processing speeds than people with MS who do not report fatigue. Similarly, Weinges-Evers et al. (2010) found that alertness, as measured by a simple RT test, was significantly slower in patients who reported fatigue. However, these cross-sectional studies did not measure RT before and after a fatiguing physical effort. These studies suggest a central role in fatigue-induced slowing of reaction time.

People with MS need to devote more cognitive reserve to walking than controls ( Hamilton et al., 2009 ), and cognitive fatigue leads to a reduction in simple RT ( Jennekens-Schinkel et al., 1988 ). Claros-Salinas et al. (2013) found that hand RT increased after a bout of treadmill walking and suggested that physical exertion leads to a measurable change in cognitive fatigue in people with MS. This study involved walking on a treadmill, at a comfortable pace, until the point of exhaustion or loss of balance. However the length of time or distance walked was not reported. Our study has shown that a deterioration in hand and foot RT can be induced by six minutes of walking, a common clinical measure used for people with MS ( Goldman et al., 2008 ). Furthermore we have highlighted the effect of this motor impairment in relation to a functional stepping task.

To date clinical research has had little success in finding an objective measure that accurately reflects the levels of perceived fatigue in people with MS. Morris et al. (2002) found no change in gait parameters between morning and afternoon in subjects with MS despite an increase in perceived fatigue. Frzovic et al. (2000) also showed that an increase in perceived fatigue from morning to the afternoon did not result in changes in clinical balance measures. A more recent study by Gervasoni et al. (2012) showed that a group of people with MS who walked on a treadmill to the point of maximum exertion also did not show changes to balance as indicated by the Berg Balance Scale and Dynamic Gait Index. These findings are indicative of the insensitivity of these clinical measures for identifying the effects of fatigue on physical function. Our study shows that walking not only induces perceived fatigue, in agreement with Crenshaw et al. (2006) , but also leads to a measurable decline in simple and choice RT performance. These RT measures show promise as more sensitive and objective clinical measures of fatigue-related motor impairments.

The slowing of simple hand RT induced by the physiologically unrelated task of walking is potentially indicative of an effect of walking-induced fatigue on central processing. Age-related slowing of RT has been suggested to be due to changes in the peripheral and central nervous system, which may include loss of myelin ( Sturnieks et al., 2008 ). Our finding that choice stepping RT movement time was unchanged yet response time was significantly slower following the six minute walk agrees with previous research into the neurophysiology of central fatigue in people with MS. Morgante et al. (2011) demonstrated that central motor conduction time and resultant RT is significantly prolonged in MS patients due to a functional impairment of the motor areas involved in planning and preparation. This lack of pre-movement facilitation was greater with higher degrees of fatigue. They concluded that frontal lobe impairment is associated with fatigue in MS related to functional impairment of the motor system at the cortical level, upstream from the corticospinal tracts ( Morgante et al., 2011 ). Similarly, studies utilising electroencephalography indicate a central origin of fatigue in MS during a simple motor task ( Leocani et al., 2001 ). Lyon and Day (1997) suggest that the central nervous system judges the trajectory of the movement of the lower limb when stepping before swing phase, thereafter the leg acts in a ballistic manner of control, removing the need for appreciable mid-step adjustment. This may explain why the movement time when stepping remained unaffected by walking-induced fatigue in our study.

The significant slowing of choice stepping RT has important functional relevance, as falls are a serious problem for people with MS and slower voluntary stepping is associated with falls in this ( Hoang et al., in press ) and other populations (Dite and Temple, 2002 and Lord and Fitzpatrick, 2001). Furthermore, slower RT has been shown to be correlated with poor performances in several clinical measures of gait and balance in older adults ( Cho et al., 2004 ). People with mild MS (EDSS 1–3.5) ( Sosnoff et al., 2012 ) display a significantly longer double support time when walking, and this is present even in those with no clinical impairments (EDSS 0-2) ( Benedetti et al., 1999 ), suggesting that a delayed stepping time when walking is present even before many other symptoms of MS are identifiable. The addition of the cognitive dual task of walking when talking increases double support time in MS ( Kalron et al., 2010 ). Our study also demonstrates that as little as six minutes of walking results in a slowing of stepping RT which has potentially important implications for mobility levels and fall risk. Further research into the effects of six minutes of walking on gait should therefore be undertaken. Newman et al. (2007) showed that the time spent in the stance phase of gait can be significantly reduced by aerobic treadmill training which gives promise to therapeutic approaches that aim to improve these aspects of motor impairment in people with MS.

We have attributed the slowing of hand RT potentially to an effect of walking-induced fatigue on central processing, but acknowledge that this link needs to be confirmed by utilising a direct measurement technique such as Transcranial Magnetic Stimulation. Our study implies fall risk is increased with walking-induced fatigue as it has been shown that increased choice stepping RT is a risk factor for falls in people with MS ( Hoang et al., in press ). However, we acknowledge these findings are indirect as we did not measure fall risk directly by retrospectively or prospectively recording falls. Future studies could build on these findings by examining whether fatigue-induced RT changes exacerbate fall risk in people with MS. We also acknowledge that the addition of measures of physiological conduction time, temperature, effort and mood in multivariate models may have added further insight into delineating the contribution of fatigue to the observed changes in reaction time. The study findings have implications for exercise participation and fall prevention interventions for people with MS. Further studies are needed to identify efficacious programs for maximising strength and balance while minimising changes of reaction times

5. Conclusion

Simple hand, foot and choice stepping RT deteriorate as a result of six minutes of walking in people with MS, which reveals an important underlying motor impairment. Further studies are needed to investigate the clinical relevance of walking related fatigue and the possible functional consequences this may have to walking, balance and fall risk. This has important implications for therapeutic interventions aimed at increasing mobility, managing fatigue and reducing risk of falls in this population.

Conflict of interest statement

The authors state that there is no conflict of interest arising from the materials presented in this article.


This project was funded by Multiple Sclerosis Research Australia (MSRA) incubator grant number 00045 and by Foundation Daw Park. The funding organisations had no influence in the project design, the collection and analysis of data, or in the preparation of the manuscript.


  • Andreasen et al., 2010 A.K. Andreasen, P.E. Spliid, H. Andersen, J. Jakobsen. Fatigue and processing speed are related in multiple sclerosis. Eur J Neurol. 2010;17:212-218 Crossref
  • Bailey et al., 2007 A. Bailey, S. Channon, J.G. Beaumont. The relationship between subjective fatigue and cognitive fatigue in advanced multiple sclerosis. Mult Scler. 2007;13:73-80 Crossref
  • Bakshi, 2003 R. Bakshi. Fatigue associated with multiple sclerosis: diagnosis, impact and management. Mult Scler. 2003;9:219-227 Crossref
  • Benedetti et al., 1999 M. Benedetti, R. Piperno, L. Simoncini, P. Bonato, A. Tonini, S. Giannini. Gait abnormalities in minimally impaired multiple sclerosis patients. Mult Scler. 1999;5:363-368
  • Cho et al., 2004 B. Cho, D. Scarpace, N.B. Alexander. Tests of stepping as indicators of mobility, balance, and fall risk in balance-impaired older adults. J Am Geriatrics Soc. 2004;52:1168-1173 Crossref
  • Claros-Salinas et al., 2013 D. Claros-Salinas, N. Dittmer, M. Neumann, A. Sehle, S. Spiteri, K. Willmes, et al. Induction of cognitive fatigue in MS patients through cognitive and physical load. Neuropsychol Rehabil. 2013;23(2):182-201 Crossref
  • Crenshaw et al., 2006 S.J. Crenshaw, T.D. Royer, J.G. Richards, D.J. Hudson. Gait variability in people with multiple sclerosis. Mult Scler. 2006;12:613-619 Crossref
  • Dite and Temple, 2002 W. Dite, V.A. Temple. A clinical test of stepping and change of direction to identify multiple falling older adults. Arch Phys Med Rehabil. 2002;83:1566-1571 Crossref
  • Dobkin, 2008 B.H. Dobkin. Fatigue versus activity-dependent fatigability in patients with central or peripheral motor impairments. Neurorehabil Neural Repair. 2008;22:105-110
  • Frzovic et al., 2000 D. Frzovic, M.E. Morris, L. Vowels. Clinical tests of standing balance: performance of persons with multiple sclerosis. Arch Phys Med Rehabil. 2000;81:215-221
  • Gervasoni et al., 2012 E. Gervasoni, D. Cattaneo, A. Montesano, J. Jonsdottir. Effects of fatigue on balance and mobility in subjects with multiple sclerosis: a brief report. ISRN Neurol. 2012;10.5402/2012/316097
  • Goldman et al., 2008 M.D. Goldman, R.A. Marrie, J.A. Cohen. Evaluation of the six-minute walk in multiple sclerosis subjects and healthy controls. Mult Scler. 2008;14:383-390 Crossref
  • Hamilton et al., 2009 F. Hamilton, L. Rochester, L. Paul, D. Rafferty, C.P. O׳Leary, J.J. Evans. Walking and talking: an investigation of cognitive-motor dual tasking in multiple sclerosis. Mult Scler. 2009;15:1215-1227 Crossref
  • Hoang et al., 2014 P.D. Hoang, M.H. Cameron, S.C. Gandevia, S.R. Lord. Neuropsychological, balance and mobility risk factors for falls in people with multiple sclerosis: a prospective cohort study. Arch Phys Med Rehabil. 2014; 10.1016/j.apmr.2013.09.017 (in press)
  • Huisinga et al., 2011 J.M. Huisinga, M.L. Filipi, K.K. Schmid, N. Stergiou. Is there a relationship between fatigue questionnaires and gait mechanics in persons with multiple sclerosis?. Arch Phys Med Rehabil. 2011;92:1594-1601 Crossref
  • Hutchinson et al., 2009 B. Hutchinson, S.J. Forwell, S. Bennett, T. Brown, H. Karpatkin, D. Miller. Toward a consensus on rehabilitation outcomes in MS: gait and fatigue. Int J MS Care. 2009;11:67-78 Crossref
  • Jennekens-Schinkel et al., 1988 A. Jennekens-Schinkel, E. Sanders, J. Lanser, E. Van der Velde. Reaction time in ambulant multiple sclerosis patients: Part I. Influence of prolonged cognitive effort. J Neurol Sci. 1988;85:173-186 Crossref
  • Johansson et al., 2007 S. Johansson, C. Ytterberg, I.M. Claesson, J. Lindberg, J. Hillert, M. Andersson, et al. High concurrent presence of disability in multiple sclerosis. Associations with perceived health. J Neurol. 2007;254:767-773 Crossref
  • Kalron et al., 2010 A. Kalron, Z. Dvir, A. Achiron. Walking while talking – difficulties incurred during the initial stages of multiple sclerosis disease process. Gait Posture. 2010;32:332-335 Crossref
  • Kurtzke, 1983 J.F. Kurtzke. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33:1444-1452
  • Lee et al., 1991 K.A. Lee, G. Hicks, G. Nino-Murcia. Validity and reliability of a scale to assess fatigue. Psychiatry Res. 1991;36:291-298 Crossref
  • Leocani et al., 2001 L. Leocani, B. Colombo, G. Magnani, F. Martinelli-Boneschi, M. Cursi, P. Rossi, et al. Fatigue in multiple sclerosis is associated with abnormal cortical activation to voluntary movement – EEG evidence. Neuroimage. 2001;13:1186-1192 Crossref
  • Lord and Fitzpatrick, 2001 S.R. Lord, R.C. Fitzpatrick. Choice stepping reaction time: a composite measure of falls risk in older people. J Gerontol Ser A: Biol Sci Med Sci. 2001;56:M627-M632 Crossref
  • Lord et al., 2003 SR Lord, HB Menz, A. Tiedemann. A physiological profile approach to falls risk assessment and prevention. Phys Ther. 2003;83:237-252
  • Lyon and Day, 1997 I. Lyon, B. Day. Control of frontal plane body motion in human stepping. Exp Brain Res. 1997;115:345-356 Crossref
  • Martin et al., 2006 C.L. Martin, B.A. Phillips, T.J. Kilpatrick, H. Butzkueven, N. Tubridy, E. McDonald, et al. Gait and balance impairment in early multiple sclerosis in the absence of clinical disability. Mult Scler. 2006;12:620-628 Crossref
  • McLoughlin et al., 2012 J.V. McLoughlin, C.J. Barr, D. Sturnieks, S.R. Lord, M. Crotty. Effect of wearing a dorsiflexion assist orthosis on mobility, perceived fatigue and exertion during the six-minute walk test in people with multiple sclerosis: a randomised cross-over protocol. BMC Neurol. 2012;12:27 Crossref
  • Morgante et al., 2011 F. Morgante, V. Dattola, D. Crupi, M. Russo, V. Rizzo, M.F. Ghilardi, et al. Is central fatigue in multiple sclerosis a disorder of movement preparation?. J Neurol. 2011;258:263-272 Crossref
  • Morris et al., 2002 M.E. Morris, C. Cantwell, L. Vowels, K. Dodd. Changes in gait and fatigue from morning to afternoon in people with multiple sclerosis. J Neurol Neurosurg Psychiatry. 2002;72:361-365 Crossref
  • Newman et al., 2007 M. Newman, H. Dawes, M. Van den Berg, D. Wade, J. Burridge, H. Izadi. Can aerobic treadmill training reduce the effort of walking and fatigue in people with multiple sclerosis: a pilot study. Mult Scler. 2007;13:113-119 Crossref
  • Ng et al., 2004 A.V. Ng, R.G. Miller, D. Gelinas, J.A. Kent-Braun. Functional relationships of central and peripheral muscle alterations in multiple sclerosis. Muscle Nerve. 2004;29:843-852 Crossref
  • Nilsagard et al., 2009 Y. Nilsagard, C. Lundholm, E. Denison, L.G. Gunnarsson. Predicting accidental falls in people with multiple sclerosis – a longitudinal study. Clin Rehabil. 2009;23:259-269 Crossref
  • Perneger, 1998 T.V. Perneger. What׳s wrong with Bonferroni adjustments. BMJ. 1998;316:1236-1238 Crossref
  • Reicker et al., 2007 L.I. Reicker, T.N. Tombaugh, L. Walker, M.S. Freedman. Reaction time: An alternative method for assessing the effects of multiple sclerosis on information processing speed. Arch Clin Neuropsychol. 2007;22:655-664 Crossref
  • Schwid et al., 2002 S.R. Schwid, M. Covington, B.M. Segal, A.D. Goodman. Fatigue in multiple sclerosis: current understanding and future directions. J Rehabil Res Dev. 2002;39:211-224
  • Schwid et al., 1999 S.R. Schwid, C.A. Thornton, S. Pandya, K.L. Manzur, M. Sanjak, M.D. Petrie, et al. Quantitative assessment of motor fatigue and strength in MS. Neurology. 1999;53:743-750
  • Sosnoff et al., 2012 J.J. Sosnoff, B.M. Sandroff, R.W. Motl. Quantifying gait abnormalities in persons with multiple sclerosis with minimal disability. Gait Posture. 2012;36:154-156 Crossref
  • Sturnieks et al., 2008 D.L. Sturnieks St., R. George, R.C. Fitzpatrick, S.R. Lord. Effects of spatial and nonspatial memory tasks on choice stepping reaction time in older people. J Gerontol Ser A: Biol Sci Med Sci. 2008;63:1063-1068 Crossref
  • Weinges-Evers et al., 2010 N. Weinges-Evers, A.U. Brandt, M. Bock, C.F. Pfueller, J. Dorr, J. Bellmann-Strobl, et al. Correlation of self-assessed fatigue and alertness in multiple sclerosis. Mult Scler. 2010;16:1134-1140 Crossref


a Flinders University, South Australia, Australia

b Falls and Balance Research Group, Neuroscience Research Australia, Sydney, Australia

c School of Public Health and Community Medicine, University of New South Wales, Sydney, Australia

lowast Correspondence to: Flinders University, Department of Rehabilitation, Aged and Extended Care, C Block, Repatriation General Hospital, Daws Road, Daw Park, South Australia, SA 5051, Australia. Tel.: +61 882 751 103; fax: +61 8 82 751 130.