Jumpy legs

A 39-year-old man presented with worsening daytime somnolence over the last 4 years. He dated his problems to a knee operation, as it was a number of months after this that he would find his overnight sleep unrefreshing. His symptoms have worsened since then and in addition to daytime somnolence, he has had increasing daytime headaches and twitches of his legs and arms when he is tired. He has an ESS score of 18/24 (consistent with excessive daytime somnolence) and he falls asleep most days for usually about half an hour. He goes to bed at 10 p.m. and gets up at 6.45 a.m. unrefreshed. He has jumps of his legs as he goes off to sleep and his partner has noticed large jerks during sleep. He has stopped all caffeinated drinks and rarely drinks alcohol. He gave up tobacco two years ago. He had a septoplasty and interestingly slept better immediately after that when he was taking codeine for the pain.

On direct questioning, he notices that his legs become restless in the evenings and that if he doesn’t move them, they can ache—an ache that is relieved by standing up and moving around.

There is no family history of note.

Questions

1 What is the diagnosis?

2 What are the appropriate investigations?

3 How should this be treated and why may his condition have improved after the septoplasty?

Answers

1. What is the diagnosis?

He has periodic limb movement syndrome (PLMS) and restless legs syndrome (RLS). Over 80% of people with RLS also have PLMS, but the converse is not true and only about one-third of people with PLMS have RLS.

RLS is characterized by an overwhelming urge to move the legs and an associated unpleasant sensation in the legs, often described as tingling, cramping or crawling, which gradually worsens if the legs are not moved. These sensations are usually worse in the evening, and movement provides temporary relief. The typical symptoms can be easily remembered using the acronym URGE (Urge to move the legs, Rest worsens, Getting up and moving relieves, Evening preponderance). About 5% of the population is affected by RLS.

RLS needs to be differentiated from cramp (sudden onset of severe pain associated with muscle spasm and relieved with stretching), neuropathy (constant discomfort tingling), vascular insufficiency (worse with movement), arthritis (joint pain) and akathisia (intense restlessness, not usually relieved by movement and associated with neuroleptic use and drug withdrawal).

About 50% of people with RLS have a family history and there are families in which RLS seems to have an autosomal dominant inheritance with anticipation. A number of gene polymorphisms have been associated with RLS, but their role in pathogenesis is unclear. Approximately 40% have an onset before the age of 20 years, and the course tends to be intermittent but progressive. The symptoms can be worsened with stress, concomitant medication (in particular, antidepressant medication) and sleepiness. Sleep disturbance is frequent and often a presenting complaint either due to periodic limb movements or because the RLS prevents the person getting to sleep (insomnia), or on waking in the night, the RLS often prevents the person getting back to sleep. With augmentation and in more severe cases, RLS can also affect the arms and shoulders, and can lose the typical worsening in the evening (occurring occasionally throughout the day).

Periodic limb movements in sleep are brief, repetitive jerks (usually over a period of 0.5–2 seconds but occasionally up to 5 seconds) of usually the legs (arms and trunk can also be affected) that occur usually every 20–40 seconds (this can range from 5–90 seconds). These occur in non-REM sleep and can cause frequent arousals. In contrast to RLS, PLMS are more common in elderly men (>30% of people over the age of 60 years, but fewer than 5% of people under the age of 50 years). PLMS can occur throughout the night in all stages of sleep, but often show a propensity for light sleep, disrupting sleep and preventing the transition to deep sleep. PLMS can therefore present with a history of jerking, but also with daytime somnolence (not all people recognize the jerks). On occasions only the larger jerks are recognized, leading to difficulties in diagnosis, with a differential diagnosis including nocturnal seizures. There is a strong association with not only RLS but also other sleep disorders, including OSA, parasomnia and narcolepsy. Similar to RLS, PLMS can be worsened by sleep deprivation. Both RLS and PLMS can be secondary to peripheral neuropathy (especially diabetic, uraemic and alcoholic neuropathies), iron deficiency, pregnancy and, rarely, spinal cord lesions. There may also be an association with Parkinson’s disease.

2. What are the appropriate investigations?

There should be a full neurological examination looking in particular for signs of peripheral neuropathy and extrapyramidal disease. Serum ferritin should be tested. Unless the history is absolutely typical, diagnosis is usually confirmed by PSG with extra EMG electrodes on the limbs. Interestingly, associated sleep disruption is not necessarily correlated with the severity of the movements and in many cases, there is evidence of arousal just prior to the movements, suggesting that the arousal is part of the syndrome rather than merely secondary to the movement. At least four PLMS are required for a diagnosis, and mild, moderate and severe PLMS can be classified as >5, >30 and >50 PLMS per hour overnight.

3. How should this be treated and why may his condition have improved after the septoplasty?

If the serum ferritin is low, then iron should be given. This may help the condition and may also help prevent augmentation if dopamine therapy is used. Good sleep hygiene, prevention of sleep deprivation and avoidance of alcohol and caffeine can all help. Avoidance of certain medication, in particular antidepressants, can also be helpful.

The most effective treatment is a dopamine agonist, and three are licensed for RLS/PLMS—pramipexole, ropinirole and rotigotine patches. L-DOPA can also be used, but has a much greater propensity for augmentation. Augmentation is a worsening of the symptoms while on dopaminergic drugs; this is characterized by earlier onset of symptoms in the day, increased severity, decreased latency and extension of the symptoms to other parts of the body, in particular the arms. In severe cases, jerks can also occur during the day. Increasing the dose of the dopaminergic drug sometimes worsens the augmentation, and alternative therapies are usually needed.

Antiepileptic drugs, in particular pregabalin and gabapentin, but also carbamazepine and valproate, can also be effective. In addition, sedatives such as clonazepam can improve symptoms and in particular can prevent nocturnal arousals, but may have a lesser effect on the motor manifestations.

In more refractory cases and in cases of augmentation, opiates can be used. Codeine is useful in those with milder symptoms, but oxycodone, methadone and fentanyl patches may need to be used in those with more severe symptoms. Sometimes people with RLS/PLMS report improvements in symptoms after operations because of the opiate pain relief (as in this case).

A range of other medication, including baclofen and clonidine, have also been tried and reported in single cases or small case series.

Learning points

Restless legs syndrome is characterized by an uncontrollable urge to move the legs due to an uncomfortable sensation in the legs during the daytime, while PLMS causes sleep disturbance and involuntary kicking of the legs/limbs during sleep. Both conditions often co-exist.

More than four movements during sleep are required for diagnosis of PLMS.

The movements can be controlled by dopamine agonists, antiepileptic drugs or clonazepam.