Restless Legs Syndrome

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Recognized Causes of RLS

RLS is not a single disorder, but a collection of disorders with similar symptoms. RLS is divided into Secondary RLS and Primary RLS or idiopathic RLS. The fact that RLS is a “mixed bag” has complicated research, confounded investigators, and frustrated clinicians. Various medications or other treatments work in only a percentage of affected patients. Dr. M. J. Thorpy believes that RLS to be a “heterogeneous group of disorders…because no single pathophysiologic mechanism explains all the clinical features exhibited.”[5] There are around twenty or so widely recognized causes of Secondary RLS. The underlying cause of Primary RLS remains unknown.

Secondary RLS is made up of very different underlying conditions (see Fig. 1) that all somehow trigger the characteristic symptoms of RLS. The best remedy for RLS is to treat the underlying condition. The proper treatment of the underlying condition is obviously quite different for each of them. Treating the underlying condition is impossible in Primary RLS, but usually practical in cases of Secondary RLS. Despite this fact, most RLS patients never attempt to determine the underlying cause of their condition. Instead of seeking long-term correction of the underlying source of their symptoms, they simply focus on nightly symptom control in order to “just get some sleep.”

Figure 1

Recognized Causes of Secondary RLS:

  • Iron deficiency or anemia
  • Pregnancy
  • Kidney Failure
  • Venous Insufficiency or Varicose Veins
  • Arborizing Telangiectasia
  • Neuropathy
  • Fibromyalgia Syndrome
  • Parkinson’s Disease

Medications such as:

  • Antihistamines,
  • H2 antagonists
  • Lithium
  • Neuroleptics
  • Beta Blockers
  • Antidepressants – paroxetine, amitriptyline, mianserin, mirtazapine
  • Alcohol
  • Caffeine
  • Gastric surgery
  • Chronic Obstructive Pulmonary Disease
    Cancer
  • Withdrawal from vasodilators, sedatives, imipramine, or opiates
  • Cigarette Smoking
  • Myelopathy or Myelitus
  • Hypothyroidism or Hyperthyroidism
  • Acute Intermittent Porphyria
  • Peripheral Cholesterol Microemboli
  • Chronic neck pain or back pain
  • History of a back or neck operation or injury [7]

Primary RLS is an idiopathic condition because the root cause remains unknown. Primary RLS is generally felt to be the most common form, although this has never been experimentally substantiated. Primary RLS is believed to be a sensorimotor abnormality associated with central nervous system dysfunction involving abnormal brain iron metabolism and irregularity of central dopaminergic neurotransmitter pathways. A familial tendency for RLS was first noted by Ekbom in 1945. The genetic predisposition is currently under investigation, and great progress has recently been made in this area. A complex inheritance pattern is suspected, as molecular genetics have identified at least three major susceptibility loci. A family history of RLS is seen in greater than 50% of cases. Patients with familial RLS are generally younger at onset of symptoms, and have a slower progression. Despite a tremendous amount of research by undaunted investigators, the pathophysiological mechanism of Primary RLS has yet to be elucidated. For this reason, treatment of Primary RLS has focused on nightly management of symptoms rather than treating the underlying disorder. [6]

Many cases of RLS are cursorily labeled as Primary RLS without the requisite investigation needed to exclude possible secondary causes. This is unfortunate, in that Primary RLS remains a diagnosis of exclusion - to be made only when all plausible secondary causes are properly ruled out. The tacit assumption that a patient is suffering with Primary RLS precludes any hope of correcting any underlying secondary causes.

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