Restless legs syndrome and periodic limb movement syndrome

There are many types of sleep movement disorders, but they are most often considered within the context of restless legs syndrome and periodic limb movement disorder.

Periodic limb movement syndrome (PLMS) and restless legs syndrome (RLS) are more common in middle and old age. The mechanism is unclear, but the disease may develop due to a disorder of dopamine neurotransmission in the central nervous system. Disorders may occur independently or in connection with the withdrawal of a drug, or in connection with the use of stimulants and some antidepressants, or in chronic renal and hepatic failure, pregnancy, anemia and other diseases.

Periodic limb movement syndrome is characterized by repeated (usually every 20-40 sec) twitching of the lower limbs during sleep. Patients usually complain of intermittent night sleep or abnormal daytime sleepiness. As a rule, movements and short awakenings - without pathological sensations in the limbs - are not realized.

In restless legs syndrome, patients complain of a crawling sensation in their lower extremities when lying down. To relieve symptoms, patients move the affected limb, stretch it, or walk. As a result, they experience difficulty falling asleep, repeated nighttime awakenings, or a combination of both.

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Causes of Restless Legs Syndrome

The causes of these syndromes are varied: polyneuropathy, rheumatoid arthritis (>30%), parkinsonism, depression, pregnancy (11%), anemia, uremia (15-20%), caffeine abuse. The use of drugs (neuroleptics, antidepressants, benzodiazepines, dopamine agonists) or the withdrawal of some of them (benzodiazepines, barbiturates) can lead to the development of restless legs syndrome and periodic limb movement syndrome.

Primary (idiopathic):

1. sporadic and hereditary.

Secondary:

1. Deficiency of iron, vitamin _B12, folic acid (anemia).
2. Renal failure.
3. Diabetes mellitus.
4. Hypothyroidism.
5. Chronic obstructive pulmonary diseases.
6. Sjögren's syndrome.
7. Peripheral neuropathy (polyneuropathy), radiculopathy and some spinal cord diseases (myelopathy).
8. Multiple sclerosis.
9. Parkinson's disease.
10. Attention deficit hyperactivity disorder (minimal brain dysfunction).
11. Pregnancy.
12. Iatrogenic (tricyclic antidepressants, selective serotonin reuptake inhibitors, lithium, dopamine antagonists, levodopa, post-gastric resection, withdrawal of sedatives or narcotics, calcium channel antagonists).
13. Other diseases: amyotrophic lateral sclerosis, poliomyelitis, Isaacs syndrome, amyloidosis, malignancy, peripheral vascular disease (arteries or veins), rheumatoid arthritis, hyperekplexia.

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Syndromic differential diagnosis

Restless legs syndrome should be distinguished from other syndromes that are sometimes similar to it: akathisia, periodic limb movement syndrome during sleep, night cramps, physiological myoclonus during sleep. This also includes painful leg and moving toes syndrome, painful fasciculations syndrome, myokymia, causalgia-dystonia syndrome, leg pain of other origin. Anxiety-depressive syndrome with sleep disorders can sometimes manifest itself with symptoms resembling restless legs syndrome.

Sporadic and familial cases of restless legs syndrome with an autosomal dominant type of inheritance have been described. The frequency of the latter, according to the literature, varies significantly (up to 50-60% and higher). The disease can begin at any age, but its frequency increases with age. Restless legs syndrome in children is often mistakenly interpreted as hyperactivity syndrome. At the same time, restless legs syndrome is often combined with attention deficit hyperactivity syndrome.

In most cases, the symptoms are bilateral. However, a significant percentage of patients (more than 40%) report right-sided or left-sided localization of the symptom. However, the side of the symptom may change in some patients even within one day. About half of the patients report paresthesia and motor restlessness in the hands. The presence of paresthesia in the hands does not depend on the severity of restless legs syndrome, age and gender of these patients. Paresthesia is described by patients as burning, tingling, itching, pain; patients often say that this is a very unpleasant feeling that is difficult to describe in words. Paresthesia can be very short (seconds); it rapidly increases in intensity and instantly disappears when moving the limb. By an effort of will, one can only slightly delay the movement or reduce its amplitude. Many researchers believe that movements in restless legs syndrome appear as a kind of response to unpleasant paresthesia. Electrophysiological studies to date do not allow us to answer the question of whether these movements are voluntary or involuntary. The course of restless legs syndrome is usually remittent, but can be stationary and even progressive. The most effective treatments are dopa-containing drugs and clonazepam.

In about 40% of cases, restless legs syndrome is idiopathic (primary). Symptomatic restless legs syndrome may be observed in diseases such as anemia associated with iron, vitamin B12, or folate deficiency; renal failure; diabetes mellitus; hypothyroidism; chronic obstructive pulmonary diseases; polyneuropathy (most often); cervical spondylosis; spinal cord tumors, lumbosacral radiculopathy, multiple sclerosis, Parkinson's disease, peripheral arterial disease, hyperekplexia, rigid person syndrome, Huntington's chorea, amyotrophic lateral sclerosis, Tourette's disease, Isaacs syndrome. There are cases in which restless legs syndrome was observed only during pregnancy. However, in many of the above cases, it remains unclear whether the listed diseases are the cause of restless legs syndrome or only serve as a provoking factor for this syndrome. To answer this question definitively, it is necessary to prove that the frequency of restless legs syndrome in these diseases is higher than in the rest of the population. This has not yet been fully done.

Symptoms of Restless Legs Syndrome

Restless legs syndrome and periodic limb movement syndrome have many similar features (a combination of pain syndrome and involuntary movements, motor phenomena, most clearly manifested during sleep) and are often combined with each other. At the same time, there are certain differences: with restless legs syndrome, pronounced sensory disorders are noted; periodic limb movement syndrome is highly stereotypical. The common link in the pathogenesis of these syndromes is dysfunction of the cerebral and peripheral dopaminergic systems, which explains the effectiveness of levodopa drugs.

• The main manifestation of restless legs syndrome is unpleasant paresthesia in the legs (patients describe them as "discomfort", "trembling", "goosebumps", "stretching", "twitching", "tingling", "itching", etc.), usually occurring before sleep or during sleep, which leads to an irresistible need to move the legs. The sensations most often occur in the legs (in the foot, shin, knee area, sometimes in the thigh or the entire limb), rarely in the arms and legs. Usually, symptoms occur in both limbs, although they may predominate on one side. As a rule, they appear during rest or in the period preceding sleep. They can also occur at any other time of the day, more often with a long monotonous body position (for example, when driving a car). These sensations completely or partially disappear at the moment of leg movement and appear again after the movement stops. The duration of such conditions ranges from several seconds to several hours, they can occur several times a day and pass on their own. The severity of sleep-wake cycle disturbances may vary, in some cases severe sleep structure disturbances and pronounced daytime sleepiness are observed. Restless legs syndrome may have a long-term course with exacerbations and remissions. The following minimum diagnostic criteria have been proposed: (A) the need to move the limbs + paresthesia/dysesthesia; (B) motor restlessness; (C) worsening of symptoms during sleep with short-term subsequent activation or awakening; (D) worsening of symptoms in the evening or at night.
• Periodic limb movement syndrome is characterized by episodes of repetitive, stereotypical movements during sleep. The movements usually occur in the legs and consist of extension of the big toe combined with partial flexion of the knee and sometimes the hip; in some cases, the arms are also involved. Patients complain of frequent nocturnal awakenings in 45% of cases, difficulty falling asleep in 43%, daytime sleepiness in 42%, and early awakening in 11%. Considering that patients may not complain of limb movements, it should be emphasized that the combination of insomnia and daytime sleepiness suggests periodic limb movement syndrome. Polysomnography is necessary to confirm the diagnosis, which reveals increased motor activity in the legs and disruption of the structure of night sleep. The integral polysomnographic indicator of disease severity is the frequency of limb movements per 1 hour (periodic movement index); in mild form it is 5-20, in moderate form - 20-60, in severe form - more than 60.

Diagnosis of restless legs syndrome

The minimum diagnostic criteria for restless legs syndrome (RLS), according to the latest data from an international group of experts, are:

1. Imperative desires to move limbs due to paresthesia (dysesthesia) in them.
2. Motor restlessness; in this case, the patient is aware that he is forced to make movements and uses various motor strategies to alleviate or get rid of unpleasant sensations.
3. Increased or onset of symptoms at rest (when the patient is lying or sitting) and their partial or temporary elimination with movement.
4. Symptoms always worsen in the evening or at night.

Patients with restless legs syndrome are characterized by disturbances in night sleep (slow falling asleep, multiple awakenings, dissatisfaction with sleep, etc.). Most patients with restless legs syndrome also note periodic movements of the limbs during sleep, which are also one of the causes of disturbances in night sleep.

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Treatment for restless legs syndrome

The most effective drugs for restless legs syndrome and periodic limb movements are dopamine mimetics (levodopa preparations, postsynaptic dopaminergic receptor agonists, MAO type B inhibitors), benzodiazepines. Recently, gabapentin has been successfully used.

Various drugs (including dopaminergic drugs, benzodiazepines, anticonvulsants, vitamins and trace elements) have been tried and used, although none of them is a pathogenetic therapy for nocturnal myoclonus or restless legs syndrome.

Treatment with dopaminergic drugs is effective but is associated with a number of side effects, in particular, aggravation of the disease (the appearance of symptoms during the daytime), relapse (worsening of symptoms after drug withdrawal), nausea and insomnia. Quite effective with minimal side effects are the D ₂ - and D _g -dopamine receptor agonists pramipexole and ropinirole. Pramipexole is prescribed at 0.125 mg 2 hours before the onset of symptoms and, if necessary, the dose is increased by 0.125 mg every 2 nights until the therapeutic effect is achieved (maximum dose 4 mg). Worsening of symptoms with pramipexole is observed less frequently than with levodopa. Ropinerol is prescribed at 0.5 mg 2 hours before the onset of symptoms and, if necessary, the dose is increased by 0.25 mg at night (to a maximum of 3 mg).

Benzodiazepines increase the duration of sleep but do not reduce abnormal limb movements, and one should not forget about the associated phenomena of addiction and induction of daytime sleepiness. If restless legs syndrome is combined with pain, gabapentin is prescribed, starting with 300 mg before bedtime; the dose is increased by 300 mg every week to a maximum of 2700 mg. The effectiveness of opioids cannot be ruled out, but they are used as a last resort due to side effects, development of addiction and dependence.