Differential Diagnosis of Restless Legs Syndrome

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Chapter 16 Differential Diagnosis of Restless Legs Syndrome

Restless legs syndrome (RLS) continues to elude recognition and diagnosis despite a lucid description of the entity by Ekbom1 in the middle of the last century. In the latter part of the 19th century and the early part of the 20th century, RLS was believed to be a psychosomatic condition. This myth was somewhat dispelled following Ekbom’s description using the term “restless legs.” Even today, many physicians do not recognize the condition and mistake it for other superficially similar conditions. Another reason for mistaken diagnosis is that there is not a single diagnostic test for RLS. Diagnosis is entirely clinical and based on the International Restless Legs Syndrome Study Group (IRLSSG) criteria2,3 (essential, supportive, and associated) as outlined in Chapter 15. It is, therefore, incumbent on the family physicians, sleep and movement disorder specialists, neurologists, psychiatrists, internists including pulmonologists and pediatricians, to be conversant with those conditions that mimic RLS. We do not find a definite cause for RLS in most of the patients (primary RLS), but some cases of RLS are associated with other disorders or intake of certain medications. Patients with the latter cases are said to have secondary or comorbid RLS; however, whether these patients were predisposed (genetically or otherwise) to develop this condition and simply had the condition triggered by comorbidities or medications remains undetermined.

This chapter summarizes the conditions mimicking RLS and points out the distinctions from true RLS, as well as briefly addressing conditions associated with RLS. This differential diagnostic section is mostly clinically oriented.

Conditions That Mimic Restless Legs Syndrome

The conditions discussed in this section often mimic the clinical features of RLS, making it difficult to differentiate them from true RLS. These conditions do not cause RLS, but it is important for every physician dealing with RLS to be familiar with the essential features of these mimics (Box 16-1). There are two major classes of disorders that can be confused with RLS—those that involve abnormal restlessness, such as akathisia, and those that are associated with pain or discomfort in the legs.


The most important condition that mimics RLS and sometimes the most difficult to differentiate from RLS, particularly the most severe forms of RLS, is akathisia. Since Sigwald and colleagues4 in 1947 described phenothiazine-induced restlessness in a patient with Parkinson’s disease (PD), neuroleptic-induced akathisia (NIA) has emerged as an important side effect of neuroleptics in the second half of the 20th century. It is, however, interesting to note that the term akathisia was used in 1901 by Ludwig Haskovec,5 the Czech neuropsychiatrist, long before the advent of neuroleptics, and he thought that akathisia was a manifestation of hysteria. The term akathisia is derived from the Greek word meaning “inability to sit.” The next milestone in the history of akathisia was the description of motor restlessness in PD unrelated to medications by Bing6 and Sicard7 in 1923 (Bing-Sicard akathisia). In contemporary writings, NIA remains the most familiar and acceptable term. This can be acute, tardive, chronic, and related to withdrawal of neuroleptics. Clinically, there are two essential components: subjective (feeling of inner restlessness) and objective (observed motor restlessness). In 1973, the U.S. Food and Drug Administration (FDA) task force defined akathisia as “a subjective desire to be in constant motion” associated with “an inability to sit or stand still” and “a drive to pace up and down.”8 The inner feeling of restlessness, jitteriness, or fidgetiness results in forced walking (tasikinesia) and other motor manifestations. Patients have difficulty sitting still; they keep moving, cross and uncross their legs, sway and rock their whole body, march in place, and constantly shift body positions while sitting. Although motor restlessness is prominent in the legs, the whole body, including trunk and arms, manifests these restless movements, which could be synchronous, asynchronous symmetrical, asymmetrical, rhythmic, or arrhythmic, resembling choreiform rather than the voluntary and myoclonic movements seen in patients with RLS. To some extent, these movements can be suppressed temporarily, but over a more prolonged period, they are uncontrollable and involuntary. These movements are present throughout the day and may become worse in the evening, but there is no circadian pattern, unlike that noted in RLS. Furthermore, the near constant movements do not relieve the intense urge to move. The following clinical features differentiate akathisia from RLS: movements of the whole body; inability to stand still; failure to get relief from these movements; lack of a circadian pattern of not being limited to the evening; presence of these restless movements not only during inactivity but also while standing and walking as if the whole body is in constant motion; and absence of uncomfortable, disagreeable sensations in the legs (which may be present in some patients with akathisia). Furthermore, periodic limb movements, which may be present with RLS, are uncommon and not prominent features of akathisia. There is generally no positive family history for akathisia, which is another differentiating feature from RLS. History of drug exposure (mostly neuroleptics, rarely selective serotonin reuptake inhibitors [SSRIs] and other antipsychotic drugs) before the period of restlessness is an essential criterion for diagnosing NIA. Physical examination (while sitting, standing, or lying down) reveals the distinctive motor restlessness and sometimes drug-induced extrapyramidial manifestations in akathisia in contrast to normal examination in idiopathic or primary RLS. In secondary RLS, however, physical findings related to the primary conditions that are associated with RLS may be present. Polysomnographically,9 there are no distinctive features, and in rare occasions, there may be evidence of mild sleep disturbance and periodic limb movements in sleep (PLMS) in akathisia in contrast to severe sleep disturbance and presence of PLMS in at least 80% of patients with RLS. In advanced stages of RLS, some patients may complain of generalized restlessness involving the trunk and arms, and lack of significant relief by their movement, making it difficult to differentiate from akathisia; thus, advanced stages of RLS may closely resemble classic akathisia with restlessness during both the day and night and little relief despite continuous motion. In these patients, however, history will include that these patients had symptoms characteristic of RLS rather than akathisia at the onset of the illness.

Sometimes neuroleptic-induced akathisia manifests as focal akathisia (monoakathisia)10,11 characterized by rhythmic swaying of the leg while sitting and flexing the knee intermittently while standing up. Carrazana and colleagues12 described contralateral akathisia (hemi-akathisia) following a subthalamic abscess. Occasionally, patients with RLS present with a unilateral leg manifestation resembling unilateral or focal akathisia, but other distinctive features described earlier and in Chapter 15 should clearly differentiate RLS from focal akathisia. Another feature to remember is that mild cases of akathisia may demonstrate variability with only intermittent presence similar to that noticed sometimes with RLS, particularly in the early stage of the illness.

Syndrome of Painful Legs and Moving Toes

This condition is characterized by spontaneous, involuntary, and purposeless movements of the toes consisting of flexion, extension, abduction, and adduction accompanied by deep aching or pulling pain in the feet or the lower part of the legs. Since its original description by Spillane and colleagues13 in 1971, both painful and painless legs and moving toes syndrome as unilateral or bilateral presentations have been described in scattered case reports attesting to the heterogeneity of this entity. Movement of the toes does not relieve the pain, in contrast to that noted in RLS patients. The movements are not prominent during sleep and are not particularly intense in the evening. Pathophysiology of the condition remains uncertain. Most cases result from a peripheral cause, such as lumbosacral radiculapathy, or minor local trauma can bring this about, but some are caused by central nervous system lesions. Very limited study of physiologic analysis showed two distinct electromyelographic (EMG) burst patterns14: synchronous activities in the agonist and antagonist muscles in the peripheral type and alternating EMG bursts in the agonist and antagonist muscles in the central type. Polysomnographic study has rarely been performed. In our own physiologic observations including polysomnographic study,15 we noted a mixture of dystonic, myoclonic, synchronous, asynchronous, and triphasic EMG bursts suggesting complex pathophysiology, which may involve both peripheral afferent and supraspinal efferent control.

Muscular Pain—Fasciculation Syndrome

This is a rare condition characterized by widespread fasciculation that is often made worse by exercise, consumption of coffee or anxiety accompanying the occasional cramps at night, and dull, aching pain in the limbs.16 Sometimes the patient may have restlessness of the legs, but the symptoms in this condition do not necessarily improve on walking or with exercise, thus clearly differentiating them from the essential clinical features of RLS.