Vascular Sympathetic Reactivity, Muscle Fatigue, and Symptomatic Fatigue in Persons With Multiple Sclerosis

Abstract

1870 Altered cardiovascular sympathetic reactivity may contribute to muscle and symptomatic fatigue in persons with multiple sclerosis (MS). PURPOSE: To determine if sympathetic vasoconstrictor drive is increased in persons with MS and associated with fatigue during isometric exercise. The secondary purpose was to examine the interrelationships among physiological and clinical measures that could contribute to muscle and symptomatic fatigue. METHODS: Ten (7F) MS and 9 (6F) control (C) subjects performed sustained isometric dorsiflexion at 30% of maximal voluntary contraction (MVC) until target tension could no longer be maintained (Biodex). Mean arterial pressure (MAP) and heart rate (HR) were measured continuously (Finapres). Blood flow (BF) was measured in the contralateral non-active forearm every 15 seconds during exercise using venous occlusion plethysmography. Vascular resistance (VR, MAP/BF) in the forearm was calculated to indicate sympathetic vasoconstrictor drive. Subjects were also assessed for selfreported symptomatic fatigue (Fatigue Impact Scale, FIS), depression (CES-D), cognitive function (Symbol Digit Modality Test, SDMT), disability status (EDSS), and sleepiness (Epworth). Analyses were performed using ANOVA, t-tests, or Pearson correlations. Results are expressed as mean ± SD. RESULTS: There was no difference in MVC between groups (MS = 19 ± 6 vs. C = 21 ± 9 ft lbs, p = 0.677). Endurance time (ET) was significantly less in MS (MS = 187 ± 83 vs. C = 290 ± 84 seconds, p = 0.02). The increase in MAP from rest to task failure was significantly less in MS (MS = 36 ± 14 vs. C = 52 ± 20 mmHg, p < 0.05), consistent with previous findings. Neither resting forearm VR (MS = 45 ± 12 vs. C = 42 ± 14 mmHg/ml/100 ml/min, p = 0.64) nor the peak change in VR (MS = −15 ± 14 vs. C = −13 ± 15 mmHg/ml/100 ml/min, p = 0.737) were different between MS and C. Within the MS group, a significant (p < 0.05) triad of correlation was formed between disease severity (i.e. EDSS) and muscle fatigue (i.e. ET) (r = −0.635), ET and cognitive function (i.e. SDMT) (r = 0.697), and SDMT and EDSS (r = −0.786). Although symptomatic fatigue (FIS) was not associated with muscle fatigue (ET), it was associated with depression (CES-D) (r = 0.646). Sleepiness also tended to be associated with depression (r = 0.55, p = 0.09). CONCLUSIONS: Sympathetic reactivity to exercise, as indicated by VR in a non-active limb, is not altered in MS nor is it associated with muscle fatigue (i.e. ET). While as muscle fatigue is associated with disease severity and cognitive function, symptomatic fatigue is only associated with depression. Supported by the National Multiple Sclerosis Society.