Spinal Cord Stimulation for Restless Legs Syndrome
Condition: Restless Legs Syndrome; Neuropathic Pain
MeSH terms: Neuralgia; Psychomotor Agitation; Restless Legs Syndrome; Syndrome
Study type: Interventional

Summary: 
      The overall goal of this proposed study is to evaluate the underlying mechanisms of neural
      control of blood flow in the lower extremities in humans with restless leg syndrome (RLS). At
      least 15% of the general public suffers from RLS and many more may go undiagnosed. This
      unfortunate disorder leads primarily to a disturbing sensation within the patient's lower
      extremities that requires movement for relief (1, 2). The central hypothesis of our study is
      that physiological changes in lower limb blood flow as a result of thoracolumbar epidural
      Spinal Cord Stimulation (SCS) lead to the relief of RLS.
    

Detailed description: 
      Patients age 18-85 years with (n=25) and without RLS (n=25) that have recently having
      undergone Spinal Cord Stimulation (SCS) implantation (thoracolumbar) for chronic pain will be
      recruited from the Departments of Anesthesia and Neurosurgery, University of Iowa Hospitals
      and Clinics. The rationale for studying both RLS patients and non-RLS patients with chronic
      back pain is to initially test the effectiveness of Spinal Cord Stimulation (SCS) on lower
      limb blood flow in the absence of symptoms of RLS. In the non-RLS patients, we could
      determine if SCS does in fact alter limb blood flow. We hypothesize that RLS patients have
      altered muscle sympathetic nerve activity (MSNA) and blood flow correlating to severity of
      RLS symptoms, which will then be modulated by Spinal Cord Stimulation (SCS), allowing for
      resolution of symptoms in RLS with MSNA-mediated improvements in leg blood flow. We also
      hypothesize that SCS in RLS patients will reduce 24-hour ambulatory blood pressure in
      parallel with reductions in MSNA.

      Those deemed eligible to participate will be invited for 2 visits to the Translational
      Vascular Physiology Laboratory in the Clinical Research Unit (CRU) of the University of Iowa
      Hospitals and Clinics. Each of the 2 study visits are identical except for experimental
      measurements that are made at each of the five measurement time points when the Spinal Cord
      Stimulation (SCS) unit is either on or off as described below.

      Visit 1: Experimental measurements include non-invasive "gold standard" measures of limb
      blood flow and arterial stiffness including femoral artery blood flow via Doppler ultrasound,
      calf blood flow from strain gauge venous occlusion plethysmography, and arterial stiffness
      via pulse wave velocity using applanation tonometry. Additionally, participants will be asked
      to assess the current level of leg discomfort every 10 minutes while measurements are taken
      by the SIT test, a validated technique for assessing restless legs symptoms where patients
      are asked to set and rest quietly during measurement talking, moving as little as possible
      (3).

      Visit 2: Experimental measurements include direct measures of sympathetic nerve activity
      using microneurography before, during and again after administration of SCS to the patient.
      Additionally, participants will be asked to assess the current level of leg discomfort every
      10 minutes while measurements are taken by the SIT test, a validated technique for assessing
      restless legs symptoms where patients are asked to set and rest quietly during measurement
      taking, moving as little as possible (3).

      Some participates may visit the laboratory for placement of a 24-hour ambulatory blood
      pressure cuff.
    

Intervention name(s): Dual-energy X-ray absorptiometry Scan; Laboratory Measurements; Blood Flow Measurement; Continuous Blood Pressure; Partial pressure of oxygen; Microneurography; Anthropometric Measurements; John Hopkins Restless Legs Severity Scale; Continuous Blood Pressure Diary
Intervention type(s): Diagnostic Test; Other; Other; Other; Other; Other; Other; Behavioral; Behavioral
Intervention description(s): Body composition analysis will be obtained by DEXA scan.; The following labs will be obtained during the course of the study: pregnancy test (urine), glucose, insulin, catecholamine, and cholesterol (serum).; The blood flow to the arm or leg may also be measured by placing an ultrasonic probe on the skin over the femoral artery of the leg and the brachial artery of the arm.; Continuous Blood pressure cuff will worn for 2 days with spinal cord stimulator on and off (24 hour on and 24 hour off). Optional procedure.; Transcutaneous recordings will be captured to measure the partial pressure of oxygen by placing monitors on the subject's chest and foot.; The sympathetic nervous system activity to the subject's leg muscles will be measured by a tiny microelectrode placed in the peroneal nerve in the leg located just below the knee on the outer part of the leg. When the nerve is located 2 tiny sterile microelectrodes will be inserted through the skin.; Height and weight will be obtained.; Subjects will be administered questionnaires to evaluate RLS symptoms using John Hopkins Restless Legs Severity Scale.; Subjects participating in Continuous Blood Pressure monitoring will be administered continuous blood pressure monitoring compliance diary.
Other intervention name(s): DEXA; 24-hour Ambulatory Blood Pressure Cuff
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: Subjects are assigned to one of two groups based on whether they have Restless Leg Syndrome to undergo experimental measurements that are made at each of the five measurement time points.
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Epidural Spinal Cord Stimulation; Muscle Sympathetic Nerve Activity; Blood Flow