Restless arm syndrome: a rare disease?

  1. Ulrich Moser and
  2. Jasmin Schwab
  1. Bayerische Ärztekammer München, D-81677 München, Bavaria, Germany
  1. Correspondence to Dr Ulrich Moser; u-moser@t-online.de

Publication history

Accepted:31 Aug 2021
First published:20 Sep 2021
Online issue publication:20 Sep 2021

Case reports

Case reports are not necessarily evidence-based in the same way that the other content on BMJ Best Practice is. They should not be relied on to guide clinical practice. Please check the date of publication.

Abstract

Restless legs syndrome (RLS) is a common neurological disorder characterised by an irresistible urge to move the lower limbs, often accompanied by unpleasant sensations in the legs, typically occurring in the evening and at night and improving with movement. Restless arms syndrome (RAS) predominantly affects the arms, while the legs are rarely affected. RAS appears to be very rare, with very few cases described to date, but the diagnosis of RAS is probably made too infrequently, especially for milder and transient forms. The patient reported here even had severe symptoms for years that could have indicated RAS. He observed an immediate improvement in all RAS-related symptoms after administration of 100 mg L-dopa +25 mg benserazide, which continues to this day. Clinicians should always be alert for RLS-like symptoms in one or both arms that worsen at rest and improve with movement, thinking of possible RAS.

Background

Restless legs syndrome is a neurological disorder with an irresistible urge to move the lower limbs, often accompanied by unpleasant sensations in the legs that worsen at rest and in the evening and improve with movement.1 2 The underlying mechanism of symptom shifting in RLS from the legs to the arms to exclusive involvement of the arms is not known.3

The prevalence of RLS is between 1.9% and 4.6%, when the criteria of frequency, severity and consideration of differential diagnoses are applied. It is thus one of the most common neurological disorders.4 In contrast, only very few patients with symptoms exclusively in the arms have been described so far.3 This suggests that restless arms syndrome (RAS) may be an extremely rare disorder. However, the true prevalence of RAS is largely unknown. The considerable time lag from the onset of symptoms to RAS diagnosis reflects the diagnostic difficulties, which are certainly related to the atypical topography. The diagnosis of RAS may, therefore, be too infrequent, especially in milder and transient forms.3

The terms primary (idiopathic) and a secondary (symptomatic) form of RLS have now been largely abandoned. Current disease theories support a model in which the presence of genetic predisposing factors and acquired risk factors, together with environmental influences, increase the risk of RLS.5–7

The underlying pathomechanism of RLS is still not fully understood. Based on the symptoms and possible therapeutic approaches, changes in iron metabolism, dopamine balance and the endogenous opioid system are the focus of current discussion.2 8–10

The main pathophysiological mechanism appears to be the oxygenation of both central and peripheral neuronal tissue, associated with dysregulation of iron transport across the blood–brain barrier and reduced iron storage in the brain. Iron is an essential cofactor of tyrosine hydroxylase, an important enzyme in dopamine synthesis, so iron and dopamine metabolism in the brain are closely linked.2 10

Strong improvements in RLS symptoms after administration of dopaminergic agents suggested a possible dopaminergic deficit in the brain and led to the idea of a dopamine pathophysiology in RLS. However, recent studies describe a more complex and partly surprising role of dopamine metabolism in the brain in connection with RLS. Contrary to expectations, synaptic dopamine production is actually increased.2 11–13 Thus, there is an apparent contradiction in that dopamine agonists improve RLS symptoms even though there is obviously an excess of dopamine in the brain. The explanation is that, on the one hand, dopamine can cause postsynaptic downregulation of striatal dopamine-2 receptors2 13 14 and, on the other hand, it has a clear circadian pattern of activity that decreases in the evening and night and increases in the morning.10 If cerebral dopamine levels are increased and at the same time dopamine receptors are reduced, it may well be that the increased dopamine stimulation is sufficient during the day. At night, there may be a relative lack of dopamine, which can be balanced then by a low dose of dopamine in the evening. However, this can lead to further downregulation of the striatal dopamine 2 receptors and thus to a worsening of RLS symptoms, called augmentation.2 10 13–15

Despite the specificity of the clinical symptoms, a large number of patients are still unrecognised or misdiagnosed.15 To address this, in 2014, RLS experts from the International RLS Study Group (IRLSSG) established new diagnostic criteria by consensus.1 The IRLSSG criteria require the presence of five essential clinical features (see box 1) and are particularly important to consider for atypical variants such as RAS.

Box 1

Diagnosis criteria for restless legs syndrome/restless arms syndrome (RLS/RAS)

Essential diagnostic criteria (all must be met)

  1. An urge to move the legs usually but not always accompanied by, or felt to be caused by, uncomfortable and unpleasant sensations in the legs.

  2. The urge to move the legs and unpleasant sensations begin or worsen during periods of rest or inactivity such us lying down or sitting.

  3. The urge to move the legs and unpleasant sensations are partially or totally relieved by movement, such as walking or stretching, at least as long as the activity continues.

  4. The urge to move the legs and any accompanying unpleasant sensations during rest or inactivity only occur or are worse in the evening or night than during the day.

  5. The occurrence of the above features is not solely accounted for as symptoms primary to another medical or a behavioural condition (eg, myalgia, venous stasis, leg oedema, arthritis, leg cramps, positional discomfort, habitual foot tapping).

Supportive criteria

  1. Family history of RLS/RAS among first-degree relatives.

  2. Dopaminergic treatment response.

  3. Periodic leg movements during wakefulness or sleep, lack of profound daytime sleepiness.

Thus, the patient’s subjective description of symptoms and no instrumental examination is required to confirm the diagnosis.1

To assess response to dopaminergic treatment, the L-dopa Test has been introduced as a supportive criterion, which has a high sensitivity (80%–88%) and a 100% specificity. Almost all RLS patients show at least an initial effect after administration of L-dopa or low doses of dopamine agonists.16

Case presentation

The patient reported here is now 66 years old and has a pain in his entire back as well as in his shoulders and arms for over 20 years.

In addition to the back pain, sleep disturbances have increased more and more. Uncontrolled or involuntary movements of the arms have occurred more frequently since that time, and although the patient communicated these facts to his therapists, no further attention was paid to this detail. During this time, he visited specialists in radiology, neurology, orthopaedics, rheumatology and nuclear medicine, but they were unable to help him sustainably. Therapeutic interventions for his musculoskeletal and psychosomatic complaints included non-steroidal anti-inflammatory drugs (NSAIDs), level II opioids, acupuncture, various injections, physiotherapy, massage, transcutaneous electrical nerve stimulation, chiropractic, sleep hygiene interventions and four inpatient rehabilitation interventions. The first presentation to the pain therapist (the author) was in March 2017, and the pain character at that time was pressing, stabbing and boring (figure 1).

Figure 1

Pain presence body scheme in March 2017. Pain character: pressing, stabbing and boring.

At this point, an inpatient rehabilitation programme focusing on behavioural therapy and eventually a series of sessions of trigger point anaesthesia of the right infraspinatus muscle and acupuncture treatment proved temporarily effective for the patient’s psychosomatic and musculoskeletal problems. At a follow-up appointment for pain management in October 2020, the patient now reported severe pain and a feeling of restlessness in both hands and forearms, which had increased significantly for about 2 years, while the back and shoulder pain had diminished. His cotreating orthopaedic surgeon diagnosed a D1-3 snapping finger of the left hand, which he managed surgically, and osteoarthritis of the wrists, which he treated with local and systemic NSAIDs. However, these measures did not change the symptoms of discomfort in the forearms and hands. The pain character was now sharp, tingling and burning (figure 2). During the day, he had no complaints, but when he fell asleep, the problems appeared. Exercise helped immediately and he always felt the need to move his arms in the evening. The patient has never had RLS symptoms in his personal history, not even in a mild form.

Figure 2

Pain presence body scheme in October 2020. Pain character: sharp, tingling and burning.

Investigations

The patient’s physical and neurological examination in October 2020 was unremarkable except for a terminal limitation of movement of the cervical spine for rotation and lateral inclination. The Jobe test of the right shoulder was slightly painful with overall free mobility of the shoulder. The Spurling test of the cervical spine was negative bilaterally; there were no sensorimotor deficits and no tapping or compression pain of the cervical, thoracic and lumbar spine. From a psychiatric point of view, there was no evidence of a current depressive disorder, but there were signs of maladaptive pain and stress processing. A polysomnogram showed a mild sleep apnoea syndrome, especially in the supine position.

In the brief pain inventory (BPI), German modified version,17 the patient rated the severity of the average pain with 8 out of 10 points on the Numerical Rating Scale of Pain (NRS), the restriction of mood with 8 and of sleep with 10 out of 10 points.

The patient fulfilled all essential IRLSSG criteria for RAS. The RLS Rating Scale (IRLS)—Score18 was 32, indicating a very severe RLS/RAS. The L-dopa test16 in October 2020 as a supportive criterion with an evening dose of Restex (100 mg L-dopa +25 mg benseracide) was promptly positive (figure 3).

Figure 3

L-dopa test in October 2020. RLS, restless legs syndrome.

Differential diagnosis

The differential diagnosis with other conditions affecting the arms must be considered and clarified by laboratory chemistry and radiology, such as shoulder arthritis, osteoarthritis, degenerative rotator cuff syndrome, muscular spasm of the upper extremity, peripheral neuropathy, venous stasis, myalgia, radicular and pseudoradicular symptoms of the cervical spine and deficiency of vitamins and minerals.1

In the present case, several MRIs of the cervical spine and one each of the thoracic spine, the lumbar spine and the right shoulder were performed in addition to corresponding radiological native images, which showed age-related degenerative changes, a c6/7 intervertebral disc protrusion and rotator cuff damage of the right shoulder (see box 2).

Box 2

Diagnoses

Pain-related diagnoses

  • Spondyloarthritis of the lumbar spine.

  • Impingement syndrome of the right shoulder.

  • Non-traumatic incomplete rotator cuff rupture right shoulder.

  • Myofascial pain syndrome, shoulder region, Tigger-Point m. infraspinatus.

  • Recurrent depressive disorder, current moderate episode.

Concomitant disorders

  • Arterial hypertension.

  • Hyperlipidaemia.

Laboratory chemistry was normal for ferritin, iron, iron saturation, renal retention values, sodium, potassium, glucose, plasma—fasting, haemoglobin A1c (HbA 1c), thyrotropin (thyroid stimulating hormone, TSH), free triiodothyronine, free thyroxine, vitamin B12 and folic acid, thus excluding deficiency of minerals and vitamins, thyroid dysfunction, diabetes mellitus and renal insufficiency (see table 1).

Table 1

Laroratory chemistry (last values in 2021, March)

Normal values
HbA1c, hemoglobin A1c; TSH, thyroid stimulating hormone.
Serum iron 89 µg/100 mL 80–150 µg/dL
Ferritin 110 ng/mL 30–200 µg/L
Iron saturation in adults 35% 16%–45%
Glucose, plasma—fasting 95 mg/dL 70–100 mg/dL
HbA1c 4.8% <5.7%
Creatinine 0.7 mg/dL 0.5–1.2 mg/dL
Glomerular filtration rate 98.3 mL/min >90 mL/min
Serum potassium 4.1 mmol/L 3.5–5 mmol/L
Serum natrium 142 mmol/L 135–150 mmol/L
tTSH 1.1 mU/L 0.3–3.5 mU/l
Free T4 1.8 ng/dL 0.5–2.3 ng/dL
Free T3 4.2 pg/mL 3.0–6.0 pg/mL
Vitamin B12 940 pg/mL 310–1100 pg/mL
Foilc acid 9.2 ng/mL 3–15 ng/mL

Outcome and follow-up

The patient reported immediate improvement in his RAS-related symptoms, which continues to this day on an evening dose of 100 mg L-dopa +25 mg benserazide. The patient’s IRLS score is persistently 10 (figure 3), mean pain on the NRS is now 3 out of 10, mood impairment is 0 and sleep quality impairment is 3 out of 10 on the BPI, German modified version (see figure 4).17 The patient reported neither side effects nor the occurrence of augmentation.

Figure 4

NRS course of complaints. NRS, Numerical Rating Scale.

Discussion

Very few RAS patients meeting IRLSSG criteria have been described to date, suggesting that RAS may be an extremely rare disease. However, the exact prevalence of RAS is largely unknown.3 As in the present case, the long time span between symptom onset and RAS diagnosis, the concomitant musculoskeletal and psychosomatic disorders and, above all, the atypical topography of RAS certainly reflect the diagnostic difficulties associated with making an accurate diagnosis.3 It is possible that RAS is underdiagnosed, especially in milder and transient forms. In the reported case, adherence to pre-existing orthopaedic and psychosomatic diagnoses certainly resulted in delayed recognition of even severe RAS according to the IRLS score.

The patient reported here had symptoms that could have been suggestive of RAS for many years. In the last 2 years, these symptoms had worsened massively and the essential IRLSSG diagnostic criteria were fully met, except that the symptoms were exclusively in the upper limbs.1

Treatment strategies for RAS are similar to those for RLS. Non-pharmacological treatment options are considered only for mild cases or in conjunction with pharmacological therapy. Pneumatic compression, infrared treatment, lifestyle changes (improving sleep hygiene, changing caffeine or alcohol intake, or smoking), yoga, massage, hot baths, aerobic exercise, cognitive behavioural therapy1 2 and acupuncture19 are discussed. However, there is insufficient evidence for the efficacy of most of these treatments, but they may support pharmacological treatment in individual cases.1 2

Apart from iron substitution in the case of laboratory-proven iron deficiency, drug therapy is purely symptomatic. The indication for therapy is based on the subjective level of suffering, especially the extent of the urge to move and the sleep disturbances.20 The most specific drug therapy for RAS/RLS is L-dopa and dopamine agonists as oral drugs (pramipexole and ropinirole) or as skin patches (rotigotine). The main advantage of these drugs is the very rapid relief of symptoms with low doses, but they are often associated with the development of augmentation, which results in worsening of disease severity.2 Therefore, pharmacological treatment with calcium channel 2 ligands (alpha-2 delta drugs: pregabalin or gabapentin) has recently been recommended.2 21

The patient reported here observed an immediate improvement of all RAS-symptoms after application of 100 mg L-dopa +25 mg benseracide, which continues to this day.

No evidence of secondary RAS was found. Iron deficiency, thyroid dysfunction, diabetes mellitus and renal insufficiency could be excluded by laboratory chemistry. The patient was not taking any medication such as neuroleptics, antidepressants or anaesthetics that could have aggravated a pre-existing RAS/RLS or triggered a secondary form. Thus, primary RAS could be assumed. In the present case, however, no positive family history was reported. These findings support the thesis that RLS is a continuous spectrum with a genetic component on the one hand and an environmental or comorbid disease component on the other hand.7

Patient’s perspective

More than 20 years ago, when my physical pain was increasing more and more, I was already able to name symptoms that applied to a diagnosis made only 6 months ago. At that time, my statements were partly ignored, laughed at or associated with causes that were completely absurd to me. Since then, I have had to keep countless appointments with many specialists. Particularly popular were suggestions that I should seek psychotherapy. Enormous costs were imposed on the health system by prescribing questionable medicines, therapies and cures. The accumulated absences from work are greater than 1 year. But worse were the wrongly treated pains, the many sleepless nights and the damage to the family and personal environment. Nevertheless, it fills me with pride that I myself found a way out of this vicious circle and that I found a doctor who, with a very high degree of probability, made the right diagnosis and initiated a therapy that is still effective today.

Learning points

  • Restless arms syndrome (RAS) as a suspected variant of restless legs syndrome (RLS) may be underdiagnosed.

  • RAS should be considered according to the International RLS Study Group diagnostic criteria when RLS-like symptoms are present in one or both arms, especially if they worsen at rest and in the evening and improve with exercise.

  • A careful differential diagnosis to exclude other disorders is necessary.

  • The question of the pathophysiological basis of RAS/RLS and the role of the iron status and dopamine metabolism remains a challenging area for future research.

  • Clinicians should be aware of this rare disorder, especially since treatment with dopaminergic agonists is proving to be very effective.

Ethics statements

Patient consent for publication

Footnotes

  • Contributors UM: Treatment of the patient, conception, design, data collection, analysis, interpretation of the data and writing of the publication. JS: Cotreatment of the patient, critical revision of the publication, presentation of the case in a pain conference.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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