Restless Legs Syndrome Differential Diagnoses

  • Author: Ali M Bozorg, MD; Chief Editor: Selim R Benbadis, MD  more...
Updated: Apr 15, 2016

Diagnostic Considerations

Conditions to consider in the differential diagnosis of restless legs syndrome (RLS) include the following:

  • Akathisia
  • Neuropathy
  • Nocturnal leg cramps
  • Painful legs and moving toes
  • Vascular disease
  • Radiculopathy

Akathisia is characterized by an inner urge to move all or part of the body, without a focal sensory complaint in the limbs. Often, it does not correlate with rest or show circadian variation, and it usually results from medications such as selective serotonin reuptake inhibitors (SSRIs), neuroleptics, or other dopamine-blocking agents.[23]

Patients with neuropathy can have symptoms similar to those of RLS.[24] Typical sensory complaints include numbness, tingling, and pain. However, neuropathic symptoms also differ from RLS symptoms in that they usually are not associated with motor restlessness or helped by movement, nor do they worsen in the evening or at night. Neuropathy and RLS may coexist. RLS occurs more frequently in patients with hereditary neuropathies but not in patients with acquired neuropathies, such as diabetic neuropathy.[24]

Nocturnal leg cramps are typically unilateral, painful, palpable, involuntary muscle contractions that are often local with a sudden onset. Like RLS, they may have a circadian pattern and often occur at rest. However, nocturnal leg cramps are associated with physical changes, including a muscle hardening not seen in RLS.

Patients with painful legs and moving toes exhibit involuntary, spontaneous flexion and extension of the toes, which is usually secondary to spinal cord injury or root lesions.[20] Unlike RLS, this condition is not associated with a focal urge to move the limbs, and it does not show a clear circadian pattern.

Vascular disease (including deep vein thrombosis and claudication) must be considered. Patients with RLS have intact peripheral pulses and typically do not have edema or cool extremities. Also, vascular disease does not exhibit a circadian pattern and usually worsens with activity, not with rest.

Differential Diagnoses

Contributor Information and Disclosures

Ali M Bozorg, MD Assistant Professor, Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida College of Medicine

Ali M Bozorg, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, American Academy of Sleep Medicine

Disclosure: Received honoraria from Cyberonics for speaking and teaching; Received honoraria from UCB, Inc. for speaking and teaching.

Chief Editor

Selim R Benbadis, MD Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida Morsani College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, American Medical Association

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cyberonics; Eisai; Lundbeck; Sunovion; UCB; Upsher-Smith<br/>Serve(d) as a speaker or a member of a speakers bureau for: Cyberonics (Livanova); Eisai; Lundbeck; Sunovion; UCB<br/>Received research grant from: Cyberonics (Livanova); GW, Lundbeck; Sunovion; UCB; Upsher-Smith.


Jose E Cavazos, MD, PhD, FAAN Associate Professor with Tenure, Departments of Neurology, Pharmacology, and Physiology, Program Director of the Clinical Neurophysiology Fellowship, University of Texas School of Medicine at San Antonio; Co-Director, South Texas Comprehensive Epilepsy Center, University Hospital System; Director of the San Antonio Veterans Affairs Epilepsy Center of Excellence and Neurodiagnostic Centers, Audie L Murphy Veterans Affairs Medical Center

Jose E Cavazos, MD, PhD, FAAN is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, American Epilepsy Society, and American Neurological Association

Disclosure: GXC Global, Inc. Intellectual property rights Medical Director - company is to develop a seizure detecting device. No conflict with any of the Medscape Reference articles that I wrote or edited.

William G Irr, MD Consulting Staff, Department of Neurology Service, St Luke's Episcopal Hospital of Houston

William G Irr, MD is a member of the following medical societies: American Academy of Neurology.

Disclosure: Nothing to disclose.

Juan Latorre, MD Research Fellow, Department of Physical Medicine and Spinal Cord Injury Medicine, The Institute for Rehabilitation and Research

Juan Latorre, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation

Disclosure: Nothing to disclose.

Erasmo A Passaro, MD, FAAN Director, Comprehensive Epilepsy Program/Clinical Neurophysiology Lab, Bayfront Medical Center, Florida Center for Neurology

Erasmo A Passaro, MD, FAAN is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, American Medical Association, and American Society of Neuroimaging

Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; UCB Honoraria Speaking and teaching; Pfizer Honoraria Speaking and teaching; Forest Honoraria Speaking and teaching

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Reference Salary Employment

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