Motor Fatigue in Multiple SclerosisJenny Thain - MS Clinical Specialist Physiotherapist, Dr Martin Wilson - Consultant Neurologist

Background• One of the most disabling

consequences of Multiple Sclerosis (MS) is impaired walking speed and/or distance resulting in impaired mobility. Observations in clinical practice suggest a distinct subgroup of these patients with ‘motor fatigability’. These patients typically demonstrate good strength on examination but report gradual reduction in speed of mobility over distances.

Aim• To test the hypothesis there is a

group of MS patients who demonstrate ‘exercise induced conduction block’ in contrast to those with fixed weakness due to irreversible axonal damage.

Design• Prospective, observational study • 6 Minute Walk and Repetitive

Stimulation Test• 10 participants with MS who reported

a fatiguing weakness in lower limb when walking (‘MS motor fatigue’ group)

• Compared with 4 MS patients who did not report fatiguing weakness (‘MS control group’)

• EDSS 3 – 6 (both groups)• Good or normal muscle strength

(both groups)

Analysis• With statistical support, analysis was

conducted on all the complete data sets using appropriate tests

• One data set from the MS Motor Fatigue group was excluded on advice from the statistician as it skewed all the other data sets

• Analysis involved exploring the raw data in various ways with comparative tests depending on the distribution of the generated data

Results:• Sample of results are presented• MS Motor Fatigue group N = 9• MS Control Group N = 4• No significant differences between groups for gender, age,

time since diagnosis, mean EDSS (Table 1) and muscle grades

Table 1: Group Characteristics  Gender Time Since Diagnosis

(months)Age (Years) EDSS

Female Male Median IQR Range Median IQR Range Median IQR Range

 Study Group

MS Fatigue Group (N = 9)

3 6 72 88.5 26 - 240 47 9.5 39 - 54 4 1.8 4 - 6

MS Control Group N = 4

3 1 29 20.3 11- 36 42 10.5 36 - 50 4.5 1.5 4 - 6

Total Distances Walked• Distances walked for each group are shown in Chart 1• We compared the total distances walked with an expected distance

walked for a ‘healthy control comparison group’ (Table 2)

Chart 1

0

100

200

300

400

500

600

389

337

Distance walked (M)

102

104

105

107

108

109

110

111

114

202

203

204

206

Average MS Fatigue Group

Average MS Control Group

Dis

tan

ce i

n M

etre

s

Table 2: Expected Walking Distance   Gender Healthy adult

expected distance (M)Group average

distance (M)

MS FatigueGroup Male 639 351 (240 – 450)

Female 606 463(400 – 520)

MS Control Group Male 681 220 (220)

Female 569 330 (230 – 350)

• Analysis was conducted on the raw data using different distance intervals (10m, 50, 100m) to identify any trends

• Data for 50m intervals is shown in Charts 2 & 3

• No specific trends between groups were seen

• Overall both groups slowed in pace • No specific pattern of ‘motor

fatiguing’ in any individual was identified

Chart 2 Chart 3 Sub - group Analysis• Analysis was conducted on a sub-

group of participants who showed a slowed pace between the 1st 100m and last 100m (N = 8)

• No differences were identified between sub - groups for EDSS or muscle grade

• Percentage drop in speed for each sub-group was calculated (Table 3)

• Overall the MS control sub - group slowed pace less than MS Fatigue sub - group

Table 3: Sub – Group % Pace DropTotal N = 8

 MS Fatigue Group N = 6MS Control group N = 2

Participant Study Number102 105 107 110 111 114 MS Group

average202 206 Control

group average

% drop in speed 1st 50m to last 50m 6.7 20.75 10.95 10.59  20 21.42 15.06 13.89 7.57  10.73

Conclusion• No significant differences between the pre-defined groups were identified• Individual subjects did demonstrate measurable ‘motor fatigability’ (eg subjects 102, 105 & 202) though

these were not all patients who subjectively reported fatigability • A subgroup of patients exists with a specific type of motor fatigability • Future larger studies could investigate this further; for example, studying only patients who report motor

fatigability despite entirely normal power ‘on the couch’ • Some patients demonstrate motor fatigabilty without recognising this subjectively, which has implications

for identifying those patients who might benefit from potential medications to improve ambulation in MS

Acknowledgements• Participants• Dr Wilson, Consultant Neurologist,

WCFT• Sioned Davies, Physiotherapist; Karl

Owens, Physiotherapy Assistant, WCFT• Dr Paul Cresswell, Clinical

Neurophysiologist; Becky Thorpe, Clinical Neurophysiologist; Dr Radhika Manohar, Consultant Clinical Neurophysiologist, WCFT

• NRC team at WCFT• Steven Lane, Biomedical Statistician,

Liverpool University• Executive team at WCFT for the Non-

Medic Research Award 2012

References• Ng A.V. et al (2004) ‘Functional relationships of central and peripheral muscle

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strength in MS’ Neurology; 53; 743 – 750• Goldman M.D. (2008) ‘Evaluation of the six-minute walk in multiple sclerosis

subjects and healthy controls’ Multiple Sclerosis; 14; 383 – 390• Kurtzke JF (1983) ‘Rating neurological impairment in MS: An EDSS’

Neurology; 33; 1444-52• Clarkson H.M. (Ed)(2000) Musculoskeletal Assessment: Chapter 1 Principles

and Methods; Lippincott Williams and Wilkins, Philadelphia, USA; 23 – 24• American Thoracic Society (2002) ‘ATS Statement: Guidelines for the Six-

Minute Walk Test’ American Journal of Respiratory Critical Care Medicine; 166; 111 – 117