The information – restless legs syndrome

The patient’s unmet needs (PUNs)

A 48-year-old woman attends your evening surgery. ‘I’m going on holiday in a few weeks on a long haul flight. Last time I drove my husband mad because I couldn’t keep my legs still.’ Further enquiry reveals that, for years, she has noticed a strong and uncomfortable urge to move her legs at rest, particularly in bed. ‘My friend reckons it’s restless legs syndrome,’ she says, ‘So I want to be tested for it. And can I have something to take to calm it down?’

The doctor’s educational needs (DENs)

What are the diagnostic criteria for restless legs syndrome (RLS)? How may it be distinguished from other differentials such as a neuropathy?

RLS is frequently misunderstood and misdiagnosed and there is no specific diagnostic test. The diagnosis relies on a general and neurological clinical examination, detailed history and symptom description. The physician should also consider the triggers and relieving factors, as well as social, medication and family histories. There are five standardised diagnostic criteria developed by The International Restless Legs Study Group (IRLSSG) for the diagnosis of RLS. RLS can be diagnosed when all five criteria are presented by the patient:^1,2

1.       A need to move the legs, usually accompanied or caused by uncomfortable, unpleasant sensations in the legs.

2.       Symptoms are exclusively present or worsen during periods of rest or inactivity such as lying or sitting.

3.       Symptoms are partially or totally relieved by movement such as walking or stretching at least as long as the activity continues.

4.       Symptoms are generally worse or exclusively occur in the evening or night.

5.       Exclude mimics and differential diagnosis as the occurrence of the above four essential criteria must not solely be accounted for as symptoms primary to another medical or behavioural condition. The most common mimics are: myalgia, venous stasis, leg cramps, positional discomfort, habitual foot tapping.

Peripheral neuropathy does not cause RLS and is not a mimic. The symptoms of peripheral neuropathy are constant, do not have diurnal variation and are associated with reflex changes which exclude RLS. Small fibre neuropathy may mimic the sensory aspect of RLS

Most patients with RLS have periodic limb movements (PLM) which are usually subtle, repetitive dorsiflexion movements of the foot occurring every 15-30 seconds during sleep, which may be associated with EEG-defined arousals from sleep. Terms that patients use to describe the symptoms include crawling, creeping, pulling, itching, drawing, or stretching, all localised to deep structures rather than the skin. Pain and tingling paraesthesia of the type that occurs in painful peripheral neuropathy are usually absent, and there is no sensitivity to touching of the skin.

The European RLS Study Group has drawn up a differential diagnosis table that details the most common disorders that can be misdiagnosed as RLS, highlighting which of the essential criteria these disorders meet. However, the following blood tests should be performed to rule out secondary RLS:

·         iron studies

·         FBC

·         serum vitamin B12/folate

·         serum creatinine

·         urea

·         albumin levels

·         serum glucose

·         TFT

Patients with severe RLS and insomnia may require sleep studies such as polysomnography or immobilisation tests.

How often is there an underlying cause such as iron deficiency – and does correction of this usually resolve the symptoms?

The causes for RLS are not entirely known. Next to primary or idiopathic RLS as the majority of cases, there are many secondary causes and diseases triggering or increasing the symptoms. The three major reversible secondary causes of RLS are:

• iron deficiency anaemia (up to 25% of patients with RLS have low iron levels). Patients with low or borderline low ferritin level should have iron levels corrected which can sometimes completely relieve, or at least partially relieve, RLS symptoms. Low ferritin levels may also be associated with augmentation.

• pregnancy (present in 23%, usually during third trimester) 

• end-stage renal disease

Furthermore secondary RLS is also associated with the conditions listed in table 2.

If peripheral neuropathy is suspected an electrophysiological examination should be considered – electromyogram and nerve conduction studies are normal in RLS patients.

What is the epidemiology and prognosis of this condition?

Recent population-based epidemiological studies have reported prevalence of RLS to be between 5% and 15% in Europe and North America. In Asian populations a very low prevalence of RLS between 0.1% and 0.6% has been reported, although high figures comparable to Western populations are reported from South Korea. The prevalence figures vary widely depending upon the population survey and the severity of symptoms required for inclusion. It should be noted that the high prevalence rate of 15% does not refer to clinically significant RLS. RLS occurs in all ages but the prevalence increases with age, so middle-aged individuals are the most affected. RLS is a chronic disorder usually with a progressive clinical course. A hereditary component in up to 60% of RLS cases is suggested in recent clinical series’.

What non-drug measures help?

When RLS is not severe enough, there is no merit for pharmacological treatment.  Self-help measures including change in lifestyle behaviours and behavioural strategies may enable a patient to cope with symptoms of RLS. These self-directed activities may include:

Sleep hygiene:

·         sleep in a quiet, comfortable and cool environment

·         wear appropriate bed clothes (such as silk pyjama, or dressing gown)

·         go to bed and wake up at a regular hour (patient may be advised to go to bed late and waking late and alter the sleep pattern to see if this helps)

·         RLS affects usually the first part of the sleep cycle at night. A late bedtime may sometimes avoid this problem.

·         avoid the intake of caffeine and alcohol before bedtime

·         read an interesting book during the onset of symptoms

During an attack patients may benefit from:

·         using a hot or cold massage

·         bathing in hot or cold water

·         walking, stretching and exercise

·         rubbing/massaging affected limbs

·         relaxation exercises (biofeedback or yoga)

·         distracting mind by mental exercises

What medication is available, how effective is it, and what are the side effects?

Treatment is only required when the symptoms are clinically significant. The possible treatment is only symptomatic, not preventive and as RLS is a chronic disorder, it is likely that once the patient starts, the treatment will be lifelong. RLS should be treated in order to alleviate sensory and motor symptoms, improve sleep and quality of life and to prevent cardiovascular complications.

Dopaminergic agents are used as first-line treatment for RLS.  Non-ergot dopamine agonists, such as ropinirole and pramipexole as tablets or rotigotine as a patch have been recommended by the European Federation of Neurological Societies.³ They should be administered as a single evening dose and are effective for the short and long-term treatment of idiopathic RLS. If the patient shows intolerance to one agent then another dopamine agonist should be tried. Symptoms are alleviated in up to 70% of patients.

The most common treatment-related side-effect is augmentation. Augmentation is characterised by an overall increase in RLS symptom severity like a paradoxical response to treatment: symptoms increase in severity with increasing dose of the medication and an improvement following decrease in medication. It is the worst long-term problem of dopaminergic treatment of RLS and occurs using all dopaminergic agents though augmentation rates are lower using drugs with longer half-life.

Ergot dopamine agonists, such as cabergoline and pergolide, are not recommended due to the increased risk of developing cardiac valvular disease.³ Alternatively, if patients are intolerant to dopamine agonists or symptoms are not completely controlled under therapy with dopamine agonists, then levodopa, taken at bedtime, should be tried. It has shown good short-term effect but long-term use is limited – up to 80% of patients treated with levodopa will experience augmentation or rebound. Levodopa is useful for intermittent RLS and as rescue medication.

For refractory cases antiepileptic drugs (e.g. gabapentin, carbamazepine, pregabalin), benzodiazepines, hypnotics (e.g. clonazepam, zopiclone) and pain killers (e.g. codeine, tramadol, oxycodone combined with naloxone) can also be used in the treatment of RLS. A recent study has reported the efficacy of oxycodone.

Professor K Ray Chaudhuri is a consultant neurologist at King’s College Hospital and professor of movement disorders at King’s College London. He is also director of the National Parkinson Foundation International Centre of Excellence.

Dr Lisa Klingelhoefer is a research fellow at King’s College Hospital and the National Parkinson Foundation International Centre of Excellence.

Ms Yogini Naidu is a lecturer in adult nursing and healthcare at the University of West London.

RLS-UK is a registered charity dedicated to helping people who suffer with Restless Legs Syndrome (RLS). The RLS-UK website provides information and advice on the condition and is a useful resource for medical practitioners and patients. RLS-UK is also a board member of the European Alliance for Restless Legs Syndrome (EARLS).

References

1. Walters AS, LeBrocq C, Dhar A, et al. Validation of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome. Sleep Medicine, 2003; 4 (2): 121-132
2. International Restless Legs Syndrome Study Group (IRLSSG). Revised IRLSSG Diagnostic Criteria for RLS.  2012 [cited 2013 June 13 2013]
3. Garcia-Borreguero D, Ferini-Strambi L, Kohnen R, et al. European guidelines on management of restless legs syndrome: report of a joint task force by the European Federation of Neurological Societies, the European Neurological Society and the European Sleep Research Society. European Journal of Neurology, 2012; 19 (11): 1385-1396

Further reading

Mrowka M, Chaudhuri KR, Odin P. Pathophysiology of restless legs syndrome. In: Chaudhuri KR, Odin P, Olanow CW, editors. Restless legs syndrome. London and New York: Taylor & Francis and Thomson Publishing Services; 2004. pp. 37–48

Walters AS. Toward a better definition of the restless legs syndrome. The International Restless Legs Syndrome Study Group. Movement Disorders, 1995; 10 (5): 634-642