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Muscular and Gait Abnormalities in Persons With Early Onset Multiple Sclerosis

Kalron, Alon PT, MSc; Achiron, Anat MD, PhD; Dvir, Zeevi PhD

Journal of Neurologic Physical Therapy: December 2011 - Volume 35 - Issue 4 - p 164–169
doi: 10.1097/NPT.0b013e31823801f4
Research Articles

Background and Purpose: Muscular and gait abnormalities are common complaints among persons with multiple sclerosis, even in the early stages of the disease. Our aim was to evaluate peak isometric strength, major lower limb muscle fatigue, and spatiotemporal gait parameters in persons with a first neurological event suggestive of multiple sclerosis, defined as a clinically isolated syndrome (CIS).

Methods: Fifty-two individuals (36 women, 16 men) with CIS, aged 35.2 (SD = 7.2) with an Expanded Disability Status Scale score of 1.7 (SD = 1.3), participated in the study. Peak isometric torque and fatigue index were measured at the knee and ankle bilaterally as well spatiotemporal parameters of gait. Twenty-eight age- and gender-matched healthy subjects served as controls.

Results: The CIS group demonstrated increased muscle fatigue, and greater ankle muscle torque asymmetries compared with the control group. The overall fatigue index scores intensified on an average of 40% in the CIS group (27% vs 19% in controls). Participants in the CIS group walked with a larger step length difference, longer step time difference, wider base of support, and prolonged double support period compared with the control group. Positive correlations were identified between double support period and some muscle parameters.

Discussion and Conclusion: At this early stage of clinically isolated syndrome, evidence of a reduction in lower limb motor performance can already be identified. The possibility of early identification and potential for developing an intervention program that may alter treatment outcome warrants further exploration.

Multiple Sclerosis Center (A.K., A.A.), Institute of Motor Functions (Z.D.), Sheba Medical Center, Tel Hashomer, Israel; and Sackler Faculty of Medicine (A.K., A.A., Z.D.), Tel-Aviv University, Israel.

Correspondence: Alon Kalron, PT, MSc, 60 Habanim St, Herzliya, Israel (e-mail:

There are no funding sources.

The rights of human subjects were protected.

This work was performed in partial fulfillment of the requirements for a PhD degree of Alon Kalron, Sackler Faculty of Medicine, Tel Aviv University, Israel.

The authors declare no conflict of interest.

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Multiple sclerosis (MS), a progressive autoimmune disease of the central nervous system, leads to the destruction of myelin, oligodendrocytes, and axons, resulting in disability among young adults.1 General signs and symptoms noted in persons with MS include gait deficits, balance impairment, elevated motor fatigue, and the inability to fully activate muscles in the lower limb. Recently, studies have found that gait deficits appear early in the disease process, and are also observed in individuals with minimal impairments from MS.2,3 On the contrary, and to the best of our knowledge, data regarding muscle strength and motor fatigue occurring at the initial phase of MS has never been reported.

Muscle groups in the lower limbs are most commonly affected in persons with MS.47 Lambert et al7 studied 15 participants with MS (mean Expanded Disability Status Scale [EDSS] = 3.5) who experienced a 20% decline in knee flexors, extensors peak torque, and motor fatigue compared with healthy matched subjects. Similar results were found with respect to ankle dorsiflexors in ambulatory persons with MS (mean EDSS of 5.5).8 Explanations included decreased muscle cross-sectional area, reduced aerobic-oxidative energy supply components,4 decreased motor neuron firing rates,9 and decreased central neural drive.10

Not all studies demonstrated differences. One group noted a similar production of ankle dorsi flexor strength between a MS group and the corresponding control group.11 Chung et al6 found no differences between women with MS and matched controls in terms of knee extensor isometric strength. Possible explanations for these inconsistencies are inadequate measuring equipment, different measurement methods, and inclusion of individuals with MS having a wide range of neurological disabilities, demonstrated by the broad span of EDSS scores.

Muscle strength and endurance should be examined on a regular basis in persons with MS. One issue needs to be addressed, that is, at what stage of the disease process are the lower limb muscles affected and to what extent. The first neurological presentation of MS is defined as a clinically isolated syndrome (CIS). A study by Confavreux et al12 described the initial symptoms of 1844 persons with MS: 18% presented with isolated optic neuritis, 52% with symptoms and signs associated with isolated dysfunction of long tract motor, 9% with an isolated brainstem syndrome, and 21% with multifocal abnormalities. At this early disease stage, individuals may also experience mobility deficits.13,14 Previous studies, based on laboratory gait analysis performed on persons with MS having mild pyramidal signs, and those having relapsing remitting MS with minimal impairments, demonstrated reduced walking speed and prolonged double support time.3

Researchers have endeavored to determine the contribution of motor deficits to gait impairment. In 27 participants with MS with moderately affected gait, walking speed was reduced and related to hamstring peak torque.15 A case-control study demonstrated decreased strength in ankle dorsiflexors and knee extensors in 17 MS fallers compared with 33 nonfallers.16 Recently, Chung et al6 found that increased power asymmetry of the knee extensors is correlated with slower walking speed and elevated fatigue. Following a 6-month strengthening program, improved walking ability was demonstrated in 47 participants with a mean EDSS of 2.5.17

Despite these findings, the exact contribution and association between major lower limb muscle parameters and gait variables remains unclear, especially at the early stage of the disease. It is important to raise awareness of this association among professionals and individuals with early onset MS, which will assist in planning treatment protocols and clinical assessments. Therefore, our aim was to characterize the extent and association among spatiotemporal gait parameters, peak isometric strength, and motor fatigue of major lower limb muscles in persons with CIS, suspected of MS, up to 3 months from onset.

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This was an observational case control study. Fifty-two individuals with early onset CIS suspected of MS (36 women and 16 men), mean age 35.2 years (SE = 1.3, range: 20–45), volunteered to participate. All had experienced a first well-defined neurological event consistent with demyelination, confirmed by an experienced neurologist and Fazekas'18 criteria of brain magnetic resonance imaging. The neurological examination concluded with an EDSS score of individual scores for each functional system (eg, pyramidal, cerebellar, sensory). A diagnosis of possible MS was based on Poser's19 criteria (clinically probable MS C2 or clinically probable MS C3) or the revised McDonald's20 criteria.

Individuals were tested within 90 days of onset of neurological symptoms and at least 1 month following steroid therapy. Pregnant women and those with orthopedic disorders affecting gait and muscle contraction were excluded. Twenty-eight apparently healthy subjects (20 women and 8 men), mean age 32.8 years (SE = 1.2), served as controls. The study was performed at the Multiple Sclerosis Center and the Institute of Motor Functions, Sheba Medical Center, Tel Hashomer, Israel, and was approved by the Sheba Institutional Review Board. All participating subjects signed an informed consent.

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Isometric Strength and Fatigue Measurements

The peak isometric torque (PIT, in Nm) and isometric fatigue index (FI, in%) of the knee flexors, extensors, ankle plantar flexors, and dorsiflexors were measured by an isokinetic dynamometer (CYBEX 6000, Ronkonkoma, NY). Knee muscle assessment was performed in a sitting position, with the seat back tilted to an 80° angle. The subject was stabilized using chest straps, with hands grasping the handles on each side. Velcro straps were also used to stabilize the thigh and shin during contractions. The knee axis was aligned with the lever arm and axis rotation. Knee extension strength and fatigue was measured at a 45° angle (0° refers to full extension). Corresponding measurements for flexion were performed at 60°. Ankle muscle assessment was carried out in the prone position with arms placed next to and parallel to the trunk. For both plantar flexors and dorsiflexors, the ankle was placed mid-position, substantially orthogonal to the shank.

In each of the 4 PIT measurements (knee flexors, extensors, ankle plantar flexors, and dorsiflexors), the subject was instructed to exert maximal muscular tension and maintain this effort for 5 seconds. Initially, 3 submaximal efforts were undertaken, followed by 3 maximal efforts with a 1-minute break between bouts. The outcome measure was the mean value of the 3 maximal efforts. All measurements were carried out bilaterally starting with the left side. Additionally, the bilateral PIT asymmetry score was calculated as follows:

Fatigue index measurement procedures were performed following the PIT tests. Seated or lying prone as described earlier, the subject was instructed to exert maximal tension and maintain this effort for 30 seconds. This single effort was performed bilaterally. The torque signal was recorded on a computer for subsequent calculation of the FI as developed by Surakka et al.21

The FI was calculated on the basis of the area under the force-time curve (AUFC) for the entire 30-second contraction period. The initial score was equivalent to the time point of PIT within the first 5 seconds (TPIT), whereas the end-point was the PIT at t = 30 seconds. The AUFC from TPIT to endpoint was then divided by the hypothetical AUFC that would have been obtained had the subject sustained the same maximal tension throughout the test. Fatigue index was calculated as follows: FI = 100% [1 − (AUFCTPM − 30/Fmax 0,5 × {TPIT − 30})]. This outcome measure has been shown to be a reliable method for assessing motor fatigue in individuals with MS.21 The FI asymmetry score was calculated using the following formula: FI asymmetry score = [1 − (FIweaker/FIstronger)] × 100.

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Gait Analysis

Temporal-spatial parameters of gait were studied using the GaitRite system (CIR systems, Havertown, PA) to capture the following spatiotemporal parameters: gait velocity, cadence, step/stride length, step/stride time, heel to heel base of support, swing/stance time, single/double time, and percentage according to gait cycle. This system has been validated for measuring both averaged and individual step gait parameters.22 Gait assessment was performed approximately half an hour after completion of the lower limb muscle measurements. All participants walked barefoot, 3 times on the mat, at a self-selected speed. Data were reported as means of the trials.

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Statistical Analyses

Descriptive statistics were performed to determine distributions of demographic, clinical, muscle, and gait parameters. Unpaired t tests and multivariate analysis of variance tests were used to detect group differences in age, height, weight, body mass index, PIT, FI, PIT asymmetry score, FI asymmetry score, and gait parameters. The Pearson correlation was used to assess the relationship between muscle and specific gait parameters (double stance and base of support) in the CIS group only. These variables were selected because of previous findings relating gait pathologies to abnormal results. Since there were many statistical variables, multiple corrections were performed using the false discovery rate algorithm.

All analyses were performed using SPSS software (Version 15.0 for windows, SPSS Inc., Chicago, IL). Reported P values were 2-tailed, and P < 0.05 was considered statistically significant.

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CIS group

The EDSS mean score was 1.7, representing minimal neurological disability; mean pyramidal score was 1.7, mean cerebellar score 1.8, and a mean sensory score 1.9. No significant differences were found among groups as to age, gender ratio (female/male), height, weight, or body mass index. The individuals' characteristics and neurological assessment scores are summarized in Table 1.

Table 1

Table 1

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PIT (Nm) of Knee and Ankle Muscle Groups

In the CIS group, significant differences were found only for knee flexor torque, with a mean 15% reduction in strength compared with controls. Between-group differences in the plantar flexor and knee extensor torque suggest trends toward significance (P = 0.06 − 0.13). No differences were observed in the dorsiflexors. In addition, as expected, reduction of strength was not specific to the right or left limb. It is worth noting that the right and left muscle groups were calculated separately; each variable was presented as a mean of the entire group. This can be confusing when one observes the following motor asymmetry scores. In this case, calculation of asymmetry scores were initially calculated by examining the difference between the bilateral muscle groups of each individual, only then was the mean value of the group calculated. This holds true for the FI calculations as well. Peak isometric torque scores in all muscle groups are summarized in Table 2.

Table 2

Table 2

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FI (%) of the Knee and Ankle Muscle Groups

In the CIS group, all fatigue indices scores were elevated compared with healthy subjects, indicating substandard motor endurance ability. On average, FI scores were 8% higher in the CIS group (27% vs 19% in controls). Fatigue index scores in all muscle groups are summarized in Table 3.

Table 3

Table 3

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Motor Asymmetry (%) of the Knee and Ankle Muscle Groups

PIT asymmetry scores

Individuals in the CIS group demonstrated greater asymmetry of plantar flexor and dorsi flexor muscle torque than healthy subjects. Plantar flexor torque asymmetry displayed the largest dissimilarity between the groups, 15.85% in individuals with CIS compared with 4.1% in healthy subjects (P = 0.005). As for knee extensors and knee flexors, between-group differences suggest a trend toward significance (P = 0.06 for each). No differences were observed between the CIS group and controls in any of the FI asymmetry scores. Peak isometric torque and FI asymmetry scores in all muscle groups are summarized in Table 4.

Table 4

Table 4

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Gait Parameters

The CIS group demonstrated longer double support time, longer step-length difference between right and left, extended step time difference between bilateral legs, and a wider base of support compared with healthy subjects. There were no significant differences in stance, swing, single support, or cadence between individuals with CIS and controls. Gait variables in participants with CIS and healthy subjects are given in Table 5.

Table 5

Table 5

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Correlation Between Specific Gait Parameters and Muscle Scores

The potential correlation between double support time and muscle parameters was evaluated. Significantly, positive correlations were identified between double support time and the FI asymmetry score of the plantar flexors (r = 0.55, P = 0.0002), the PIT asymmetry score of the knee flexors (r = 0.52, P = 0.0004), and the PIT asymmetry score of the plantar flexors (r = 0.50, P = 0.001). However, following correction for multiple correlations, the relationships between base of support and muscle parameters did not meet significance.

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Previous studies have provided data as to muscle weakness and fatigue in individuals with MS.8,21 However, evidence of muscle decline in early MS has not previously been published. To the best of our knowledge, this study is the first to detect muscular deficits in individuals with CIS, beginning at a very early stage of the disease. We identified certain muscle and gait parameters that differed from those of healthy controls. Participants in the CIS group demonstrated elevated motor fatigue both in the knee and ankle muscle groups. Overall, motor fatigue was 40% higher than healthy subjects. Individuals with CIS exhibited decreased PIT solely in knee flexion and elevated asymmetry scores in ankle muscle groups.

Decreased strength and increased motor fatigue in persons with MS can be attributed to central or peripheral origin or both. Reduced central activation in MS has been observed as lower maximal motor unit firing rates,9 as well as incomplete activation of motor units.23

Significant changes also occur within the muscles, such as lower contraction speed,23 lower oxidative capacity, and atrophy.4 In a 2003 study, force deficits were exhibited at the single-muscle fiber level due to atrophy of type IIa fibers taken from the vastus lateralis muscle of subjects with MS. Lower force production in type I fibers was attributed to both atrophy and decreased specific tension.24 Furthermore, biopsy analyses of the tibialis anterior muscle, taken from subjects with MS (mean EDSS = 4), showed markedly smaller fibers, fewer type I fibers, lower succinic dehydrogenase activity per unit fiber volume, and a greater tendency for muscles to generate energy via anaerobic means. These results were correlated with strength and physical activity. There was a tendency for the average fiber succinic dehydrogenase activity to be inversely correlated with symptomatic fatigue. Kent-Braun et al4 suggested that the reduced maximum discharge rates and altered motor unit activation could be the primary cause of changes in skeletal muscle characteristics. Similarly, Sharma et al25 completed a wide range of neurophysiological and metabolic measurements on 28 subjects with MS. Their main results demonstrated greater muscle fatigue and delayed force recovery in subjects with MS compared with controls. Accordingly, fatigue was not due to central fatigue, peripheral fatigue of the motor nerve or myoneural junction, or from impaired excitability of the muscle membrane. They demonstrated slowed rates of force development and greater decreases in phosphocreatine and pH within the muscle itself. Therefore, the authors concluded that the excessive peripheral muscular fatigue observed in the subjects with MS originated both from impaired excitation-contraction coupling and abnormal energy metabolism.

We conclude that the basis for motor deficits is likely to be multifactorial rather than a single mechanism. According to our results, it appears that one or more of these mechanisms may occur very early in the disease process. Moreover, after carefully examining the asymmetry motor scores, it is worth noting that while the reduced peak strength had a tendency to affect the lower limbs in a unilateral pattern, motor fatigue was widely distributed, affecting both the knee and ankle muscles, bilaterally. Future studies should address this issue.

It should be emphasized that isometric muscle fatigue cannot be detected using noninstrumented methods, which is why motor fatigue was not included in the standard neurological tests and was not applied when assessing motor impairments in early MS. As stated earlier, motor fatigue, rather than weakness, was predominant in our subjects with CIS. Therefore, we advise paying special attention to lower limb muscle fatigue.

As to gait characteristics, participants with CIS walked with a larger step length and longer step time difference, a wider base of support and a prolonged double support period. Our findings are similar to those reported in previous studies performed on early and minimally impaired persons with MS.2,3 Despite this mutual consensus, it is worth noting that most of the previous studies loosely interpreted the “early” MS phase as ranging from several weeks up to 32 months. This CIS group had a very short timeframe criterion, that is, 1 to 3 months from the first demyelinating event suggestive of MS. At this initial stage, these participants revealed only mild neurological signs and no functional limitations.

Our results indicate that a possible correlation exists between gait alterations and impaired muscle performance, as demonstrated by the CIS group. We believe that the prolonged double support phase presented by persons with CIS could be a compensatory strategy intended to reduce the risk of falling, since the center of mass is at its lowest position during the double support phase, a location that improves balance reactions.

Previous reports have confirmed diverse neurological and orthopedic pathologies wherein lower limb weakness results in prolongation of the double support phase during normal walking.26 Mentz et al27 observed a positive correlation between the double support parameter to FI asymmetry of the plantar flexors and PIT asymmetry of the knee flexors and the plantar flexors, finding that prolonged double limb support and wider base of support were indicators of instability. Moreover, these parameters have been found to be associated with a preexisting fear of falling in the elderly.28

We suggest that early detection of muscular and gait abnormalities can promote intervention programs at a stage when individuals can benefit the most, thus focusing on improved ambulation and motor functional abilities. Previous studies support this contention, presenting improved gait29 and enhanced muscle activation following specific training programs.10,21,30 Gutierrez et al31 carried out an 8-week progressive strengthening program on 8 participants with MS (mean EDSS = 3.7). Upon completion, the participants demonstrated a 52% increase in plantar flexor muscle strength, positively correlating with gait kinematics.

In accordance with the present study results, we herein outline rehabilitation programs, focusing on muscle endurance. In a recent study, Dettmers et al32 carried out a low-level 3-week endurance training program. Upon completion, the participants' (mean EDSS = 2.6) walking distance significantly improved by 66%. Furthermore, following an 8-week progressive resistance training program, participants with MS (n = 13) increased lower limb muscle endurance by 84%, positively correlating to functionality.33 However, evidence relating to the ability of these intervention programs to decelerate physical disability in the long term, is still needed.

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This study had several limitations. First, in normal adults, peak muscle performance is not a requirement for routine walking. During self-selected walking speed in normal adults, gait lower limb muscles work below 50% of their maximum capability. Therefore, it is questionable whether the peak torque data are sufficiently accurate to draw conclusions regarding the self-selected speed gait. However, detecting reduced peak muscle performance is important for highly related activities such as running or jumping. Since onset of MS occurs in relatively young adults, who are frequently very active, this data could be of some value. Second, hip muscle examination was not performed. The gluteus maximus and medius affect ambulation, influencing both spatiotemporal gait parameters and activity of adjacent lower limb muscles. From the core stability perspective,34 hip muscle weakness among persons with CIS could directly and indirectly affect knee and ankle muscles, leading to spatiotemporal gait alterations. However, when there is decreased activity in multiple muscles, it is extremely difficult to differentiate primary muscle weaknesses in relation to the affected secondary muscles. A further limitation relates to the CIS group. This group was not subdivided according to clinical presentation. Although this would have lead to fewer subjects per group, focusing separately on participants presenting with optic neuritis, poly- or multisymptomatic signs could have exposed specific group outcomes.

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Clinicians should be aware of possible gait and lower limb muscle deficits very early in the MS disease process, especially in the absence of clear clinical impairment. The burden of detecting such deficits, ie, the need for instrumented measures, is likely to be offset by the positive potential of early intervention programs. The addition of other muscle groups and/or more responsive tests to the test battery may enhance our ability to understand the mechanisms underlying the evolution of MS and thereby improve the management of this disease.

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1. Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N Engl J Med. 2000;343:938–952.
2. Givon U, Zeilig G, Achiron A. Gait analysis in multiple sclerosis: characterization of temporal-spatial parameters using GAITRite functional ambulation system. Gait Posture. 2009;29:138–142.
3. Martin CL, Phillips BA, Kilpatrick TJ, et al. Gait and balance impairment in early multiple sclerosis in the absence of clinical disability. Mult Scler. 2006;12:620–628.
4. Kent-Braun JA, Ng AV, Castro M, et al. Strength, skeletal muscle composition, and enzyme activity in multiple sclerosis. J Appl Physiol. 1997;83:1998–2004.
5. Andreasen A, Jakobsen J, Peterson T, Anderson H. Fatigued patients with multiple sclerosis have impaired central muscle activation. Mult Scler. 2009;15:818–827.
    6. Chung L, Remelius J, Van Emmerik R, Kent-Braun J. Leg power asymmetry and postural control in women with multiple sclerosis. Med Sci Sports Exerc. 2008;40:1717–1724.
    7. Lambert CP, Archer RL, Evans WJ. Muscle strength and fatigue during isokinetic exercise in individuals with multiple sclerosis. Med Sci Sports Exerc. 2001;33:1613–1619.
    8. Schwid SR, Thornton CA, Pandya S, et al. Quantitative assessment of motor fatigue and strength in MS. Neurology. 1999;53:743–750.
    9. Rice CL, Vollmer TL, Bigland-Ritchie B. Neuromuscular responses of patients with multiple sclerosis. Muscle Nerve. 1992;15:1123–1132.
    10. Fimland MS, Helgerud J, Gruber M, Leivseth G, Hoff J. Enhanced neural drive after maximal strength training in multiple sclerosis patients. Eur J Appl Physiol. 2010;110(2):435–443.
    11. Kent-Braun JA, Sharma KR, Weiner MW, Miller RG. Effects of exercise on muscle activation and metabolism in multiple sclerosis. Muscle Nerve. 1994;17:1162–1169.
    12. Confavreux C, Vukusic S, Moreau T, Adeleine P. Relapses and progression of disability in multiple sclerosis. N Engl J Med. 2000;343:1430–1438.
    13. Benedetti MG, Piperno R, Simoncini L, Bonato P, Tonini A, Giannini S. Gait abnormalities in minimally impaired multiple sclerosis patients. Mult Scler. 1999;5:363–368.
    14. Karst GM, Venema DM, Roehrs TG, Tyler AE. Center of pressure measures during standing tasks in minimally impaired persons with multiple sclerosis. J Neurol Phys Ther. 2005;29:170–180.
    15. Mevellec E, Lamotte D, Cantalloube S, Amarenco G, Thoumie P. Relationship between gait speed and strength parameters in multiple sclerosis. Ann Readapt Med Phys. 2003;46:85–90.
    16. Cattaneo D, De Nuzzo C, Fascia T, Macalli M, Pisoni I, Cardini R. Risks of falls in subjects with multiple sclerosis. Arch Phys Med Rehabil. 2002;83:864–867.
    17. Surakka J, Romberg A, Ruutiainen J, et al. Effects of aerobic and strength exercise on motor fatigue in men and women with multiple sclerosis: a randomized controlled trial. Clin Rehabil. 2004;18:737–746.
    18. Fazekas F, Barkhof F, Filippi M, et al. The contribution of magnetic resonance imaging to the diagnosis of multiple sclerosis. Neurology. 1999;53:448–456.
    19. Poser CM, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple sclerosis: guidelines for research programs. Ann Neurol. 1983;13:227–231.
    20. McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the Diagnosis of Multiple Sclerosis. Ann Neurol. 2001;50:121–127.
    21. Surakka J, Romberg A, Ruutiainen J, Virtanen A, Aunola S, Mäentaka K. Assessment of muscle strength and motor fatigue with a knee dynamometer in subjects with multiple sclerosis: a new fatigue index. Clin Rehabil. 2004;18:652–659.
    22. Webster KE, Wittwer JE, Feller JA. Validity of the GAITRite walkway system for the measurement of averaged and individual step parameters of gait. Gait Posture. 2005;22:317–321.
    23. Ng AV, Miller RG, Gelinas D, Kent-Braun JA. Functional relationships of central and peripheral muscle alterations in multiple sclerosis. Muscle Nerve. 2004;29:843–852.
    24. Garner DJ, Widrick JJ. Cross-bridge mechanisms of muscle weakness in multiple sclerosis. Muscle Nerve. 2003;27:456–464.
    25. Sharma KR, Kent-Braun JA, Mynhier BS, Wiener MW, Miller RG. Evidence of an abnormal intramuscular component of fatigue in multiple sclerosis. Muscle Nerve. 1995;18:1403–1411.
    26. Perry J. Gait Analysis: Normal and Pathological Function. Thorofare, NJ: SLACK Incorporated; 1992:169–281.
    27. Mentz HB, Lord SR, Fitzpatrick RC. Age-related differences in walking stability. Age Ageing. 2003;32:137–142.
    28. Chamberlin ME, Fulwider BD, Sanders SL, Medeiros JM. Does fear of falling influence spatial and temporal gait parameters in elderly persons beyond changes associated with normal aging? J Gerontol. 2005;60A:1163–1167.
    29. Rampello A, Franceschini M, Piepoli M, et al. Effect of aerobic training on walking capacity and maximal exercise tolerance in patients with multiple sclerosis: a randomized crossover controlled study. Phys Ther. 2007;87:545–555.
    30. Dalgas U, Stenager E, Ingemann-Hansen T. Multiple sclerosis and physical exercise: recommendations for the application of resistance-, endurance- and combined training. Mult Scler. 2008;14:35–53.
    31. Gutierrez GM, Chow JW, Tillman MD, McCoy SC, Castellano V, White LJ. Resistance training improves gait kinematics in persons with multiple sclerosis. Arch Phys Med Rehabil. 2005;86(9):1824–1829.
    32. Dettmers C, Sulzmann M, Ruchay-Plossl A, Gutler R, Vieten M. Endurance exercise improves walking distance in MS patients with fatigue. Acta Neural Scand. 2009;120:251–257.
    33. de Souza-Teixeira F, Costilla S, Ayan C, Garcia-Lopez D, Gonzalez-Gallego J, de Paz JA. Effects of resistance training in multiple sclerosis. Int J Sports Med. 2009;30:245–250.
    34. Ekstrom RA, Donatelli RA, Carp KC. Electromyographic analysis of core trunk, hip, and thigh muscles during 9 rehabilitation exercises. J Orthop Sports Phys Ther. 2007;37:754–762.

    clinically isolated syndrome; gait; multiple sclerosis; muscle strength and fatigue

    © 2011 Neurology Section, APTA