1. Motor Fatigue in Multiple Sclerosis Jenny 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 GenderTime Since Diagnosis (months) Age (Years)EDSS FemaleMaleMedianIQRRangeMedianIQRRangeMedianIQRRange Study Group MS Fatigue Group (N = 9) 367288.526 - 240479.539 - 5441.84 - 6 MS Control Group N = 4 312920.311- 364210.536 - 504.51.54 - 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 Table 2: Expected Walking Distance GenderHealthy adult expected distance (M) Group average distance (M) MS FatigueGroupMale639351 (240 – 450) Female606463(400 – 520) MS Control GroupMale681220 (220) Female569330 (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 1 st 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 Drop Total N = 8 MS Fatigue Group N = 6 MS Control group N = 2 Participant Study Number 102105107110111114MS Group average 202206Control group average % drop in speed 1 st 50m to last 50m 6.720.7510.9510.59 2021.4215.0613.897.57 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 alterations in multiple sclerosis’ Muscle and Nerve; 29; 843-852 Schubert M. et al (1998) ‘Walking and Fatigue in multiple sclerosis: the role of the corticospinal system’ Muscle and Nerve; 21; 1068 – 1070 Schwid S.R. et al (1999) ‘Quantitative assessment of motor fatigue and 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