Pramipexole Alters Thermoregulation in Restless Legs Syndrome

Abstract

Study Objectives: Previous studies have associated restless legs syndrome (RLS) with peripheral hypoxia and impaired thermoregulation in the lower extremities. We performed longterm monitoring of skin temperatures in order to investigate whether these fi ndings could be explained by reduced blood fl ow to the peripheral tissues. Methods: 96-hour continuous measurements of skin temperature were performed both in the distal and proximal parts of the body of 15 patients with RLS and 14 healthy controls. During the recording, the patients participated in suggested immobilization tests both with and without pramipexole medication. Results: We found no baseline differences in distal or proximal skin temperature between patients and controls in daytime or during immobilization. However, pramipexole signifi cantly increased distal skin temperature in the patient group during immobilization (31.1°C vs. 32.9°C, p < 0.05). Daytime temperatures were not affected by therapy or disease status. Conclusions:The data suggest that patients with RLS and healthy controls have similar blood fl ow to the peripheral skin tissue. Pramipexole, however, alters thermoregulation and the previous studies might have been biased by medication. Dopaminergic medication is a major confounding factor when assessing peripheral phenomena in RLS and should be controlled for in the future studies. S C I E N T I F I C I N V E S T I G A T I O N SR estless legs syndrome (RLS), recently known as Willis-Ekbom disease, is associated with discomfort precipitated by immobility in the evening hours.1 Traditionally, RLS is believed to be of central origin, but recently RLS has also been associated with several fi ndings suggesting peripheral abnormalities. Most importantly, a recent study suggested the appearance of peripheral hypoxia during immobilization in patients with RLS.2 In addition, the skeletal muscles of the legs of RLS patients have been shown to have higher capillary tortuosity 3 and up-regulated vascular endothelial growth factor (VEGF).4 These fi ndings imply that these patients suffer from peripheral hypoxia. The hypoxia could result from insuffi cient blood fl ow to the legs either during daytime or only during immobility. To assess this hypothesis, continuous blood fl ow measures are warranted in RLS patients.Continuous measurement of skin blood fl ow may be achieved by measuring changes in skin temperature. Skin temperatures are commonly measured both distally and proximally, and a distal-to-proximal gradient (DPG) is calculated to assess the blood fl ow to the distal parts of the body.5 Distal skin temperature rises at sleep onset while the DPG of skin temperature shifts closer to zero, coinciding with the increase in melatonin secretion. 6 These data show that DPG is a selective tool for continuously assessing the thermoregulatory blood fl ow.Body temperature could be an important factor in RLS. Thermal hypoesthesia, on the other hand, is associated with secondary but not idiopathic RLS.9 Recently, it was demonstrated that RLS could be as...

Therapeutic advances in restless legs syndrome (RLS)

“…Interestingly, and perhaps associated with this finding, RLS was high (29.7%) in patients presenting to a neuromuscular department with exercise intolerance . Whether peripheral hypoxia also can explain some of the frequent comorbidities in RLS, and whether these findings, including pramipexole having an effect on thermoregulation in RLS, can facilitate development of new treatments remains to be established.…”

Cardiovascular comorbidity in patients with restless legs syndrome: current perspectives

“…The authors postulated that findings in prior studies of altered blood flow and microcirculation may be related to a dopaminergic treatment effect, rather than RLS. 89 Finally, a study using ultrasound measurements of brachial artery flow-mediated dilatation found poorer vascular endothelial function in RLS patients compared with controls, supporting the involvement of the peripheral vascular system in RLS generation. 90 In summary, the above lines of evidence support the involvement of hypoxic pathways and peripheral vascular system involvement in RLS pathophysiology, mechanisms that have been associated with increased risk of CVD.…”