Restless Legs Syndrome

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Treatment of RLS

The diagnosis of RLS should be made or rejected using the 2003 NIH criteria. Severity of symptoms can be determined with the IRLS Scale. The RLS Differential Diagnosis should be analyzed and conditions that mimic RLS should be ruled out. Difficult or unusual cases can be clarified by asking about RLS Risk Factors, supportive clinical features, and by performing a SIT test or PSG.

Once the diagnosis of RLS is confirmed, possible secondary causes should be considered and corrected before the diagnosis of Primary (idiopathic) RLS is entertained. Only by treating underlying secondary causes can RLS patients achieve long-term symptom relief, thus avoiding chronic drug therapy geared at daily symptom control. Unfortunately, Primary and Secondary forms of RLS cannot be differentiated based on their clinical characteristics. A thorough search for possible underlying secondary causes should be conducted. A serologic work-up should be done that includes “an assessment of blood urea nitrogen (BUN), creatinine, fasting blood glucose, glucose tolerance, complete blood count, serum ferritin, magnesium, thyroid-stimulating hormone, and folate levels. Needle electromyographic (EMG) and nerve conduction studies can be considered if polyneuropathy is suspected clinically, even in the setting of an apparently normal neurologic examination.” [7]

“Primary RLS is generally felt to be a condition in which an abnormal nervous system is reacting inappropriately to relatively normal legs. In RLS patients with venous disease, it appears that RLS is due to a relatively normal nervous system reacting appropriately to abnormal legs.”

As mentioned above, Dr. Ekbom noted in 1944 that one of his initial eight RLS patients had varicose veins. He suspected “venous congestion and an accumulation of metabolites” to be a cause of RLS and concluded that: “It is possible that the condition is due to a functional vascular disorder.” [3,4,8] The connection between RLS and venous disease did not receive any further attention until 1995, when Dr. A.H. Kanter published his groundbreaking study. Dr. Kanter’s study reinforced the evidence that RLS can be caused by varicose veins when he found sclerotherapy to be 98% effective in the initial relief of RLS symptoms. Dr. Kanter concluded that all patients with varicose veins and RLS should be considered for phlebological evaluation and possible treatment before being consigned to chronic drug therapy. [12]

Our 2008 Phlebology article described the results of a prospective, randomized, unblinded, parallel two-group, pre-post-test study funded by the American College of Phlebology, in which we performed Endovenous Laser Ablation (EVLA) of refluxing superficial axial veins using the CTEV 1320nm laser and ultrasound guided sclerothrapy of associated varicosities with foamed sodium tetradecyl sulfate (STS). This study showed that operative correction of superficial venous insufficiency (SVI) in patients with SVI and RLS decreased the mean IRLS score by 21.4 points, corresponding to an average 80% improvement in RLS symptoms. We concluded that operative correction of SVI alleviates RLS symptoms in patients with SVI and moderate to very severe RLS, and recommended that SVI should be ruled-out in all RLS patients before drug therapy is initiated or continued. [14]

It is becoming more apparent that, in an unknown percentage of RLS cases, the symptoms are secondary to underlying venous disease. Many of these patients have subtle physical findings not likely to be discovered with a cursory physical examination. RLS patients should therefore be properly evaluated for venous insufficiency by a vascular ultrasound technician familiar with the nuances superficial venous reflux (not simply the standard DVT evaluation). Any RLS patient found to have arborizing telangiectasias, varicose veins, or venous insufficiency should be referred to an experienced phlebologist (refer to www.phlebology.org to find a phlebologist in your area) for appropriate evaluation and treatment. [12,14]

Once any known secondary causes have been ruled out, the patient is assumed to have Primary RLS. At this point, appropriate treatment of PrimaryRLS should be initiated. This typically begins with Nonpharmacologic Measures, which work for mild to moderate cases of Primary RLS. Medications that provoke RLS should be avoided. Lifestyle should be modified, including avoidance of caffeine, nicotine, and alcohol. A sleep routine should be planned and strictly followed. Regular moderate exercise should be incorporated into daily routines. Graded compression stockings can be tried (typically worn during the day and removed at night). Individual behavioral coping strategies vary, but include behavioral modifications that have proven generally effective, as outlined by patient-expert Jill Gunzel on her website www.rlsrebel.com and in her book Restless Legs Syndrome: The RLS Rebels Survival Guide. [15] The RLS Foundation is an up-to-date source for RLS news and treatment options. It maintains a list of local patient support groups on its website www.rls.org, as well an on-line discussion board where RLS sufferers discuss what works and what doesn’t work for them.

Firgure 1

Nonpharmacologic Measures

  • Avoid caffeine
  • Quit smoking
  • Cut back on alcohol
  • Baths
  • Massages
  • Leg vibration
  • Relaxation techniques
  • Warm or cool packs
  • Establish good sleep hygiene.
  • Have a cool, quiet, comfortable sleeping environment
  • Go to bed at the same time each night
    get out of bed the same time each morning
  • Get regular moderate exercise the same time daily
  • Stay mentally alert in the evening
  • Don’t fight the feeling. Get up if need be.
  • Keep a sleep diary
  • Stretch routinely

Pharmacological treatment is usually required for treatment of moderate to severe Primary RLS cases. Specialized dopamine agonists have moved to the forefront of the medical arsenal. Requip® (ropinirole hydrochloride) and Mirapex® (Pramipexole dihydrochloride) are selective dopamine agonists that stimulate D2 and D3 dopamine receptors. These medicines are quite effective in relieving RLS symptoms. In his 2005 article, Dr. M.J. Thorpy asserts that: “dopamine agonists are first-line therapy and provide symptom relief in 70% to 100% of patients.” [16] Ropinerole became the first drug to be cleared by the FDA specifically for the treatment of RLS in May 2005. Ropinerole was joined by Pramipexole in November 2006. [17] Other selective dopamine agonists are sure to follow.

As do all medications, the selective dopamine agonists have a side-effect profile (nausea, vomiting, dizziness, somnolence, syncope, fatigue, dyspepsia, etc.). In addition, they are plagued by tolerance, augmentation, and rebound when used for long-term treatment. “The development of tolerance and augmentation associated with use of dopaminergic and nondopaminergic treatments are the major complications of (medical) therapy for RLS.” [18] Other drugs may be required should these difficulties arise. Other classes of medications such as opioids, muscle relaxants, sleep medicines, medications for epilepsy, etc. have been found to be effective when the dopamine agonists are contraindicated.

Which medicine is right for a particular patient can only be determined by a consultation with a physician familiar with treating RLS. It commonly takes several trials to find the right medication and dosage, and sometimes a combination of medicines works best.

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