Some Call RLS the “Sleep Thief”

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Tuesday, January 21, 2020

January 21, 2020 Is Melatonin Right for You? If you or a loved one are affected by restless legs syndrome (RLS), then you likely suf…

January 21, 2020

Is Melatonin Right for You?

If you or a loved one are affected by restless legs syndrome (RLS), then you likely suffer from disrupted sleep. In fact, a person with moderate to severe RLS averages less than five hours of sleep per night, according to experts. Sleep deprivation is linked to many negative health effects, including depression, which can have a profound impact on a person’s day-to-day life.* Therefore, it makes sense to seek an intervention that may improve quality of life.

Many people who have difficulty sleeping turn to an over-the-counter supplement: melatonin. Melatonin is a naturally occurring hormone that is produced by the pineal gland in the brain to regulate the circadian rhythm, or the body’s internal clock. The release of melatonin is controlled by light. As daylight fades, usually one to three hours before bedtime, melatonin levels increase, which helps promote sleep. In the morning, the increase in daylight signals to the brain to halt melatonin production, aiding the transition to wakefulness.

More than 3 million adults take melatonin as a sleep aid, according to the National Center for Health Statistics. However, the effects of melatonin seem to vary; its effectiveness largely depends on the dose and timing of the supplement, as well as the sleep disorder being addressed.

Research on circadian rhythm sleep-wake disorders sheds light on the use of melatonin to improve sleep. According to the clinical guideline for treating these disorders (Auger, et al., 2015), studies have shown mixed results when administering melatonin to people whose circadian rhythm sleep-wake disorders stem from external alterations to their sleep cycles, such as shift work or jet lag. In one study, melatonin improved the length and quality of daytime sleep for people with shift work disorder in some, but not all participants. In another study of people with jet lag disorder, melatonin was more effective than the placebo for the first three days after traveling, but then lost its advantage. For circadian rhythm sleep-wake disorders that fall under the category of internal alterations in the timing of sleep, such as irregular sleep-wake rhythm, current data does not support the use of melatonin as a treatment. This may be relevant to RLS, since RLS follows a circadian pattern – that is, with most intense symptoms in the evening and nighttime hours. More research with a greater number of participants is necessary to determine the usefulness of melatonin across the board.

Nevertheless, melatonin may help one’s sleep schedule if taken at the right time and at the right dose. Typical doses of melatonin range from 0.5 mg to 5 mg. Higher doses should be avoided, even though there are many over-the-counter products available in doses as high as 10 mg. The best timing for most people is one to three hours before bedtime. It makes sense to consider melatonin as a potential option for a good night’s rest – but not necessarily for individuals with RLS; melatonin has been shown to trigger symptoms of RLS for some people. In a small study, researchers found a significant increase of sensory and motor symptoms of RLS when participants took melatonin compared to those who did not (Whittom, et al., 2010). Why is this?

Although RLS follows a circadian pattern, RLS is believed to be a sensorimotor disorder of the central nervous system. Research has shown that brain iron deficiency contributes to RLS, particularly within brain cells that contain the neurotransmitter dopamine. In terms of the sleep-wake cycle, dopamine is associated with wakefulness because it hinders the neurotransmitter norepinephrine, which then blocks melatonin release from the pineal gland. Because the human body operates under a system of checks and balances, melatonin also hinders release of dopamine in the central nervous system, thus creating a feedback loop. Since melatonin contributes to lower levels of dopamine, and lower levels of dopamine are associated with worsening RLS symptoms, some scientists suggest that melatonin may play a role in exacerbating RLS symptoms.

Another characteristic to note is that melatonin is serotonergic, which means that it is made from the same starting molecule (or building block) as serotonin – a neurotransmitter produced by the body that contributes to feelings of well-being and happiness. While serotonin’s role in regulating the sleep-wake cycle is complex, studies show that increases in serotonin reduce rapid eye movement sleep (REM sleep, the stage in sleep generally associated with dreaming) and can aggravate periodic leg movements of sleep. This is consistent with the fact that a common class of antidepressant medications that increase serotonin called selective serotonin reuptake inhibitors, or SSRIs, cause a worsening of RLS symptoms.

The bottom line is that melatonin may or may not help individuals sleep depending on many different factors. For people with RLS, it is important to know that taking melatonin comes at a risk of potentially aggravating symptoms. As always, you should to talk to your doctor before starting or stopping any treatment, even when they are marketed as naturally produced supplements.

*See Depression and RLS, available in the member portal at www.rls.org or by request.

How to Treat Restless Legs Syndrome (RLS)| Sleep Foundation

Restless legs syndrome (RLS), otherwise known as Willis-Ekbom disease, is a disorder  characterized by  uncomfortable tingling sensations and an irresistible urge to move the legs. Symptoms appear to follow the circadian rhythm, usually getting worse at night and often interfering with sleep.

Restless legs syndrome treatment aims to reduce discomfort from symptoms and improve sleep quality. While RLS symptoms may never fully go away, they can be significantly improved through a combination of lifestyle changes, vitamin and mineral supplements, medical devices, and medication.

Establishing a Treatment Plan for Restless Legs Syndrome

When treating RLS, doctors must consider the severity of the condition and the extent to which it affects your quality of life. Due to the potential for side effects, doctors may prefer to avoid prescribing medication for mild symptoms that don’t interfere with day-to-day life.

Since RLS can occur on its own or as a result of another medical condition, treatment for RLS symptoms may need to be approached differently depending on the root cause. Before proceeding with RLS treatment, experts recommend looking for other conditions that could be causing or aggravating RLS symptoms. Common culprits include:

• Sleep deprivation
• Stress
• A sedentary lifestyle
• Obesity
• Alcohol, nicotine, caffeine use
• Pregnancy
• Diabetes
• Sleep-disordered breathing
• Peripheral neuropathy
• Renal insufficiency
• Medication such as antihistamines and certain antidepressants

For many people, addressing these factors may lead to a drastic reduction in RLS symptoms. However, if symptoms are still bothersome, or if they interfere with sleep, doctors may advise additional remedies.

Restless Legs Syndrome and Nutrition

Many cases of RLS are associated with iron deficiency, which can be  treated with iron supplements. These have few side effects apart from stomach complaints and constipation, and they work to reduce symptoms of RLS in many people with low iron and ferritin levels or iron-deficiency anemia. After checking your iron and ferritin levels, your doctor may prescribe iron supplements alone or in conjunction with other medications.

Other vitamins and minerals such as magnesium, zinc, and vitamin D may also play a role in RLS. Pregnant women in particular may benefit from folate supplements, while people with kidney problems may benefit from vitamin C and E supplements.

Home Remedies for Restless Legs Syndrome

Home remedies offer a simple way to improve RLS symptoms. Though more research is needed to confirm how effective these methods are, many people with mild to moderate RLS symptoms find relief from a combination of the following:

• Moving the legs: Moving the affected body part usually leads to  relief from uncomfortable sensations, though symptoms may return when movement ceases.
• Implementing healthy sleep hygiene habits: RLS can cause sleep loss , but it’s also exacerbated by sleep problems. Try to keep a regular sleep schedule and ask your doctor for personalized sleep hygiene tips.
• Avoiding tobacco and eating a healthy diet: The Restless Legs Syndrome Foundation recommends reducing alcohol, caffeine, sugar, and salt and following a healthy diet rich in vitamins and minerals. In addition to relieving RLS symptoms, a healthy diet can help improve sleep quality.
• Exercising: Moderate exercise and stretching may help reduce RLS symptoms. That said, people with RLS should be careful with high-intensity activity, which may cause muscle cramps and stiffness that can exacerbate symptoms.
• Receiving massages or self-massaging: Some people find relief from RLS symptoms after massaging affected areas.
• Using heat or cold: RLS-related discomfort can often be tamed by applying a hot or cold compress or taking a warm bath before bed. Response to temperature may vary from person to person.

Researchers have also proposed acupuncture, electrical stimulation, transcranial magnetic stimulation, sclerotherapy for varicose veins, infrared light, yoga, and other methods for relieving RLS symptoms. However, there is limited research on whether these treatments are effective, and whether the benefits outweigh the risks.

Medical Devices for Restless Legs Syndrome

New attention is being given to the possibility of using medical devices to improve RLS symptoms. Similar to the way that moving the legs gives temporary relief, these medical devices aim to reduce discomfort of RLS symptoms by providing external stimulation.

So far, the Food and Drug Administration (FDA) has approved two medical devices as RLS treatments: a compression foot wrap and a vibrating pad. Both are available by prescription and designed for people with moderate to severe RLS.

The foot wrap works by applying targeted pressure to the affected area, usually the lower leg or foot. By contrast, the vibrating pad uses counter-stimulation to mask RLS symptoms and improve sleep quality. Both devices are considered fairly safe, though they may not be suitable for people with certain underlying health conditions.

Some physicians also recommend using a pneumatic compression device to ease RLS symptoms. It’s thought that compression of the veins helps boost circulation and reduce the uncomfortable sensations caused by RLS.

Restless Legs Syndrome Medication

Medication is currently considered the gold standard for people with moderate to severe RLS. To reduce the risk of unpleasant side effects, always work with a doctor to find the medication that’s right for you.

People with RLS resulting from another condition, or those with another consideration such as pregnant women, children, people with anxiety or depression, or individuals with kidney disease, may need to exercise extra caution when taking medication(s).

RLS can be treated with several different families of medications, the most common being dopamine agonists and anti-seizure drugs.

Dopamine Agonists

Drugs that target dopamine receptors are one of the most effective treatments for RLS. Dopamine agonists can be taken in pill form approximately two hours before bedtime or administered continuously through a patch. The FDA has currently approved three dopamine agonists for RLS: pramipexole, ropinirole, and rotigotine.

A major side effect of dopaminergic drugs is augmentation (progressive worsening) of RLS symptoms, which can come in many forms. Symptoms may appear earlier in the day, they may become more intense, they may spread to other parts of the body, or higher doses of the drug may be needed for it to remain effective. These side effects could be mistaken for a natural progression of RLS, but they are typically reversed once the patient stops using the drug. Adjusting the drug’s timing and dosage  may reduce augmentation.

Other potential side effects include a rebound of symptoms in the morning, a growing tolerance to the drug, nausea, dizziness, sleepiness, insomnia, orthostatic hypotension, and impulsive or compulsive behaviors such as gambling.

Anti-Seizure Drugs

Anti-seizure drugs are often used for people who experience pain along with their other RLS symptoms. These drugs are gaining popularity as an RLS treatment because they seem to work as well as dopaminergic agonists, but are less likely to cause augmentation of RLS symptoms.

The FDA has approved gabapentin enacarbil for use in RLS, preferring it over standard gabapentin because it has fewer side effects. Another similar drug, pregabalin, also shows promising results for RLS symptoms and sleep quality, and carries a low risk of side effects.

The FDA warns that anti-seizure drugs may cause dangerous breathing difficulties, especially for people already at risk, such as the elderly or those with lung disease, and for those who are also taking opioids or benzodiazepines. nti-seizure drugs can also cause augmentation of RLS symptoms, though they are not as likely as dopaminergic drugs to do so. Finally, people taking anti-seizure drugs can experience problems with dizziness, fatigue, and sleepiness.

Benzodiazepines

Benzodiazepines don’t have a direct effect on RLS symptoms, but they may help individuals with RLS sleep more soundly.

Because of the potential for developing a tolerance, most doctors prescribe benzodiazepines only if other drugs don’t work. People with sleep apnea may find that benzodiazepines make their symptoms worse. Benzodiazepines can also cause next-day sleepiness, fatigue, and difficulty concentrating.

Opioids

Low doses of opioids are a last-line treatment for people with severe RLS symptoms that do not respond to other treatments.

Opioids are highly addictive, and most people develop a tolerance that leads to them needing higher and higher doses over time. Other side effects of opioids include constipation, nausea, dizziness, and worsening of sleep apnea.

Other Drugs

A few substances, such as valerian and valproic acid, are sometimes used to treat RLS despite not being FDA-approved. Due to the lack of research on their efficacy and side effects, the American Academy of Sleep Medicine recommends against using these for RLS.

Tips for Coping With Restless Legs Syndrome

Learning to recognize and avoid your personal triggers can help you manage RLS over time.

Effective techniques for minimizing RLS symptoms vary from person to person. Many people find relief from keeping active throughout the day and using acupuncture, massage, stretching, or relaxation techniques at night. During the day, you may be able to ward off RLS symptoms by keeping your mind busy even when you are sitting still with activities like reading or chatting to a friend.

Though RLS is not life-threatening, the frustration of not being able to sleep well can take a toll on mental health. Cognitive behavioral therapy, support groups, or reaching out to family and friends may provide additional emotional resources for coping with RLS.

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Circadian Rhythm of Restless Legs Syndrome: Relationship with Biological Markers

Pain syndromes are quite common in Parkinson’s disease, in addition to the motor defect, can significantly worsen the quality of life. Various types of pain related to PD have been described. Different clinical characteristics of the pain, variable relationship with motor symptoms, and variable response to dopaminergic drugs, as well as, in some cases, the dependence its appearance in a specific time of the day, suggest that pain in PD has a complex mechanism with the widespread impairment of the sensory information transmission at different levels of the CNS. In addition to the dopaminergic systems of the brain and spinal cord, non-dopaminergic systems (nor epinephrine, serotonin, gamma-amino butyric acid, glutamate, endorphin, melatonin) are also involved in the development pain syndromes in PD. A neurodegenerative process associated with PD establishes a new dynamic balance between the nociceptive and antinociceptive systems, which ultimately determines the level of pain susceptibility and the pain experience characteristics. Basal ganglia along with amygdala, intralaminar nuclei of the thalamus, insula, prefrontal cortex, anterior and posterior cingulate cortex determine the motor, emotional, autonomic and cognitive responses to pain. A Abstract-Pain syndromes are quite common in Parkinson’s disease, in addition to the motor defect, can significantly worsen the quality of life. Various types of pain related to PD have been described. Different clinical characteristics of the pain, variable relationship with motor symptoms, and variable response to dopaminergic drugs, as well as, in some cases, the dependence its appearance in a specific time of the day, suggest that pain in PD has a complex mechanism with the widespread impairment of the sensory information transmission at different levels of the CNS. In addition to the dopaminergic systems of the brain and spinal cord, non-dopaminergic systems (nor epinephrine, serotonin, gamma-amino butyric acid, glutamate, endorphin, melatonin) are also involved in the development pain syndromes in PD. A neurodegenerative process associated with PD establishes a new dynamic balance between the nociceptive and antinociceptive systems, which ultimately determines the level of pain susceptibility and the pain experience characteristics. Basal ganglia along with amygdala, intralaminar nuclei of the thalamus, insula, prefrontal cortex, anterior and posterior cingulate cortex determine the motor, emotional, autonomic and cognitive responses to pain. Therefore, the treatment of pain syndromes in patients with PD should be based on profound fundamental knowledge about this problem and have a multidisciplinary approach.

Restless Legs Syndrome – Sleep Education by the AASM

August 2020 |  Reviewed by:  Reeba Mathew, MD and Imran Shaikh, MD

What is restless leg syndrome?

Restless legs syndrome is a neurological sleep disorder that causes you to have uncomfortable feelings and the urge to move your legs. Restless legs syndrome makes it difficult to get comfortable enough to fall asleep. The symptoms are usually worse in the evening and at night. The sensation is difficult for some people to describe. It has been described as a crawling or creeping sensation. You may lie down and begin to feel itching inside your legs. If you move your legs or get up and walk around, these symptoms may go away. The discomfort may return when you try again to go to sleep.

In some restless legs syndrome cases, you may have trouble sitting still for long periods. Long car rides or airplane travel may be difficult.

Many people wait years to seek treatment because they do not view it as a serious concern. If left untreated, you may notice that your symptoms become more frequent and severe.

Restless legs syndrome may cause you to get fewer hours of sleep each night. Many people with severe cases get less than five hours of sleep per night. Milder cases do not disturb your sleep as much, though the sleep may be of poorer quality.

The accumulated sleep loss from restless legs syndrome can make you excessively sleepy during the daytime, cause you to be irritable and make concentration difficult. This may have a major impact on your professional and personal life. People with restless legs syndrome are more likely to have depression or anxiety.

Restless legs syndrome is usually manageable through medication and lifestyle changes.

Most people develop restless legs syndrome after age 45 although it can develop at any age. Women are nearly twice as likely as men to develop the disorder. If you have a family member with restless legs syndrome, you are more likely to develop the symptoms before you are 45 years old. More than half of people with restless legs syndrome have a pattern of it in their family, as the risk is about three to six times greater.

Frontiers | Restless Legs Syndrome: From Pathophysiology to Clinical Diagnosis and Management

Background

The symptoms of the RLS were first described by Willis (1685) and then published by Ekbom (1960). Despite being introduced hundreds of years ago, it’s still a poorly recognized disorder because of the unclear pathophysiology and relatively low morbidity, resulting in limited recognition by primary care physicians and common misdiagnosis and under-diagnosis. RLS is considered as a common neurological sensorimotor disorder that manifests as an irresistible urge to move the body to relieve the uncomfortable sensations. There’s a significant circadian rhythm of the RLS, as it commonly worsens at night.

Epidemiology

It has been concluded that the prevalence rate ranged from 3.9 to 15% of the general population (Ohayon et al., 2012) from recent epidemiologic analyses of different countries. The estimated prevalence of the RLS is around 7–10% in Caucasians (Ohayon et al., 2012) while there is a much lower incidence ranging from 0.1 to 12% among Asian population (Cho et al., 2009; Tsuboi et al., 2009; Chen et al., 2010; Panda et al., 2012; Shi et al., 2015). Compared with other countries, RLS is much more common in western countries. As numerous studies in western countries indicated the prevalence of 10, 10–15, and 5.5% in United States, Canada, and Europe (United Kingdom, Spain, Germany, Italy), respectively (Phillips et al., 2000; Ohayon and Roth, 2002). On the other hand, studies from Asian countries showed a pretty low prevalence rate of RLS. The first Indian population study on RLS revealed a prevalence of 2.9% (Panda et al., 2012) while a prevalence of 0.96% among inhabitants of Ajimu in Japan who were older than 65 years old (Tsuboi et al., 2009). Another RLS study in Shanghai, China revealed a prevalence rate of 1.4% among 2941 eligible individuals older than 18 years old (Shi et al., 2015). The significant difference between different ethnic populations may be due to different genetic background, ethnicity, geography, and environmental influences including natural environment and diet habits. The different populations targeted, research methodologies and diagnosis criteria used may contribute to this result as well.

Most surveys have concluded that the prevalence and severity of the RLS both increase with age (Phillips et al., 2000; Ohayon and Roth, 2002), suggesting that the neurodegenerative process may play an important role in RLS. Life style of older people and the senile changes including cardiovascular changes and metabolism changes is also related to RLS (Koh et al., 2015; Cassel et al., 2016). In adults, the incidence of RLS is twice as high in women than in men (Berger et al., 2004), which may result from the hormones such as estrogen and progesterone and different social roles.

The age of onset varies widely from childhood to over 90 years of age. Though most patients in clinical practice are middle-aged or older, juvenile onset is not rare. 38–45% of adult patients complain about first symptoms before the age of 20 (Walters et al., 1996; Montplaisir et al., 1997). A study in 2007 found rates of 1.9 and 2.0% in 8–11 years old and 12–17 years old children and adolescence, respectively. Another study using a different diagnostic criteria for RLS in children that published in 2003 revealed a prevalence of 5.9% (Kotagal and Silber, 2004). A newest pediatric RLS diagnostic criteria that include consideration of typical words used by children, differential diagnosis and comorbidity was published in 2013 (Picchietti et al. , 2013). But no gender difference is found in pediatric RLS (Per et al., 2017). This gender difference in adult but not in children might be due to pregnancy because nulliparous women have about the same prevalence of RLS as males (Berger et al., 2004). The different classifications of RLS including primary and secondary RLS may also contribute to these findings. Sleep, mood, cognition, and quality of life are significantly affected in pediatric RLS patients (Picchietti and Picchietti, 2010). And ADHD, depressive symptoms, and anxiety are very common comorbidities of pediatric RLS patients (Pullen et al., 2011).

Clinical Presentations and Diagnostic Criteria

Clinical Presentations

Restless legs syndrome manifests as an overwhelming urge to move the body to relieve the uncomfortable sensations, primarily when resting, sitting, or sleeping. The uncomfortable feelings are always described by the patients as “creeping, crawling tingling, tingling, pulling, or painful” deep inside the limbs (Trenkwalder et al. , 2005), unilaterally or bilaterally occurring with the knees, the ankles or even the whole lower limbs (Trenkwalder et al., 2005). Sometimes even the phantom limbs can be involved (Skidmore et al., 2009). Commonly it affects the patient’s sleep. Insomnia is the most common reason for a patient with RLS to search for consult in clinical practice. The most common bedtime problems caused by RLS is difficulty initiating sleep (Mohri et al., 2008). It has a significant circadian pattern which presents as worsening symptoms in the evening and short remission in the morning after waking up (Kushida et al., 2007). The longer the course of the disease, the more likely the symptoms affect the arms or the other places of the body besides the legs. It’s not uncommon that patients developed arm restless syndrome with progressive disease (Freedom and Merchut, 2003). Movement such as walking, stretching, or bending the legs relieves the discomfort at least temporarily and partially (Trenkwalder et al. , 2005).

Restless legs syndrome affects the patient’s HRQoL to different degrees according to various severities of the symptoms. HRQoL is measured by 36-Item Short Form Health Survey (SF-36), a 36 item survey used to construct eight scales among physical and mental health and health transition. Most patients have mild symptoms, only 11.9% of them seek for consult, while about 3.4% of all the patients need drug treatment (Hening, 2004). The main morbidities except for extreme discomfort were sleep loss and disruption of normal activities (Trenkwalder et al., 2005). Patients with mild or moderate symptoms manifested discomfort with less frequency, lower severity, and less influence of the symptoms on their sleep. Comparing with the general population, patients with severe or very severe RLS symptoms always reported apparent deficits (10–40 points on 100-points scales) in physical functioning, bodily pain, general health, vitality, social functioning, role-physical, and role-emotion (Trenkwalder et al. , 2005). With deficient sleep at night, severely affected patients might complain about having difficulty in their daily life including their jobs and social activities (Kushida et al., 2007). A significant higher probability of 25% with ADHD were found in RLS patients compared to general population (Pullen et al., 2011). On the other hand, 20% of ADHD patients meet criteria for RLS as well (Zak et al., 2009; Yilmaz et al., 2011). Pathophysiological pathways of ADHD remains poorly understood, but the most popular theory is the dopamine deficit theory, which could be a shared pathway with RLS (Swanson et al., 2007). BTBD9, a RLS risk allele, may be related to certain subtypes of ADHD, which responds well to iron supplementation treatment (Schimmelmann et al., 2009). Disruption of sleep length and quality, daytime alertness can contribute to depression and anxiety. Increasing sympathetic tone due to PLMS may lead to cardiovascular disease and high blood pressure (Stevens, 2015).

Different from in adults, pain is a common presentation in pediatric RLS. 45% of children use the terms pain and hurts or hurting which makes growing pains a common misdiagnosis in pediatric RLS (Picchietti et al., 2013). And children always use their own words like “need to move, want to move and got to kick (Picchietti et al., 2011)” to describe “urge”. ADHD is also a very common comorbidity in pediatric RLS. Except for bad impact on sleep, mood and cognition, behavioral and educational changes are very common in pediatric RLS (Picchietti et al., 2013). It might be due to disruption of homework and ability to concentrate.

Associated Features

Circadian Rhythm

Both sensory and motor symptoms show significant circadian rhythm in RLS, which display as a peak at similar time at night. A study showed the increase in melatonin secretion to be the only changes preceding the sensory and motor symptoms in RLS patients, indicating melatonin might affect the symptoms by its inhibitory effect on dopamine secretion in central nervous system (Michaud et al. , 2004). The intensity of RLS symptoms peaks on the falling phase of the core body temperature, another endogenous marker of circadian rhythm, while it decreases when core temperature increases (Hening et al., 1999; Barriere et al., 2005).

Previous studies have shown that plasma dopamine and its metabolites changes with circadian rhythm not only just in humans (Sowers and Vlachakis, 1984), but also in CSF in primate animals (Perlow et al., 1977) and in the striatum of rat (Schade et al., 1995; Castaneda et al., 2004). Another study indicated that the dopamine receptor responsiveness is modulated by the circadian rhythm at the level of spinal cord in decapitated Drosophila melanogaster (Andretic and Hirsh, 2000). Moreover, it has been revealed that sensitivity of dopamine receptors increased at night at the level of tubero-infundibular-dopaminergic system (Garcia-Borreguero et al., 2004). Additionally, a circadian variation of serum iron paralleled the CSF dopamine, as well as the severity of symptoms (Garcia-Borreguero et al. , 2004). However, it is unclear whether the brain iron concentrations changes would follow this pattern.

Periodic Limb Movement Disorder

Periodic limb movement disorder, previously known as nocturnal myoclonus, is defined as involuntary movements of the patient’s limb or torso during awake or sleep which the patient is not aware of, different from the voluntary movement of the limb to relieve the discomfort in RLS patients (Hening et al., 1999; Trenkwalder et al., 2005). Nevertheless, it’s a very common phenomenon in RLS patients. A previous study indicated that PLMS was found in around 80% of RLS patients (Montplaisir et al., 1997). On the contrary, not a large percentage of patients having PLMS presented RLS. PLMS, which is not a specific feature for RLS patients, can be associated to many other conditions. The PSG is usually employed to measure the movements, while actigraphy is a helpful method for diagnosing and measuring PLMW or PLMS. PLMS is diagnosed on PSG by at least continuous four muscle contractions lasting 0. 5–10 s and recurring during intervals of 5–90 s. The minimum amplitude of a leg movement event is an 8 μV increases in EMG voltage above resting EMG (Iber et al., 2007) in diagnostic criteria for PLMD.

A movement in PLMS starting in sleep can continue when waking up and vice versa. On the other hand, arousals happening before or during a movement event do not change the assessment of that event (Iber et al., 2007). Immobilization test is to measure PLMW in which the patient is asked to lie perfectly still. The PSG records the time the patient can stay still and the limb movements during an hour. It can be used to quantify the severity of RLS, to follow up the patient’s course of disease and to monitor treatment response (Trenkwalder et al., 2005).

Diagnostic Criteria

The diagnostic criteria have experienced a lot of improvements and revisions in the history, including the earliest informal Ekbom’s “criteria” for RLS in 1960, then DCSAD restless legs DIMS or DOES syndrome – essential features in 1979, ICSD diagnostic criteria for RLS in 1990, IRLSSG “minimal” criteria for diagnosis of RLS in 1995 and NIH/IRLSSG (NIH) “essential” criteria for diagnosis of RLS in 2003 (Allen et al. , 2014). On the basis of previous diagnostic criteria, the four essential diagnostic criteria of RLS published by NIH/IRLSSG in 2003 emphasized the importance of the urge to move the legs in diagnosing RLS. The four essential criteria are shown below (Table 1).

TABLE 1. 2003 NIH/IRLSSG diagnostic criteria.

Although, 2003 NIH/IRLSSG diagnostic criteria have defined RLS in a much more detailed way than those previous criteria. The same disadvantage still exist in this criteria, RLS “mimics” can’t be excluded according to this diagnostic criteria. Such as conditions like cramps, positional discomfort and local leg pathology. Then the diagnostic criteria were recently revised again by the IRLSSG in 2012 (International Restless Legs Syndrome Study Group, 2012). Comparing with 2003 NIH/IRLSSG diagnostic criteria, 2012 revised RLS diagnostic criteria have added an important essential criterion, noting that RLS should be differentiated with other conditions with similar symptoms such as myalgia, venous stasis, leg edema, arthritis, habitual foot tapping, and so on (International Restless Legs Syndrome Study Group, 2012). 2012 revised RLS diagnostic criteria also stated the stipulation of clinical course and clinical significance of RLS as presented (International Restless Legs Syndrome Study Group, 2012). The newest diagnostic criteria (Table 2) is much more rigorous than 2003 IRLSSG diagnostic criteria.

Specifier for clinical significance of RLS emphasizes that the influence of RLS on the patient’s function in social, occupational, educational, or other important areas should be evaluated. Different from in adults, functional consequences of RLS in children are mainly behavioral and educational domains (Arbuckle et al., 2010). The new diagnostic criteria set up a more rigorous method to ascertain a RLS case with more specific criteria and excluding standards. It has improved the validity of RLS diagnosis. On the other hand, it helps to classify the patient’s clinical course and clinical significance which helps the physician to better monitor the progression of RLS and support better cases for research samples (Allen et al. , 2014). The specifier for clinical course does not apply for pediatric RLS or special cases of RLS secondary to pregnancy or medication (Picchietti et al., 2013). Generally, mild RLS severity with no family history, and young age at RLS onset are predictors of RLS remission. While most patients with severe RLS show a chronic clinical course (Lee et al., 2016).

Periodic limb movement during sleep is a very identified sign in RLS patients. It is found that 80–89% of RLS patients have excessive PLMS than same aged people (Montplaisir et al., 1997). PLMS is not very specific for RLS since it is a frequent condition among adults aged over 45 years (Hornyak et al., 2007). When PLMS present in a pattern different than expected for age excluding the states of other disease or medication, PLMS can support the diagnosis of RLS.

Considering that children might not understand the term “urge”, simple straightforward prompts should be asked, like “Do your legs bother you?” or “Do your legs bother you at night?” And common descriptions used by children about RLS sensations are “need to move, want to move and got to kick (Picchietti et al. , 2011)”. RLS mimics like ADHD, sore leg muscles, growing pains and dermatitis should be carefully considered when diagnosing pediatric RLS (Picchietti et al., 2013).

Comparing with the previous diagnostic criteria, 2012 revised RLS diagnostic criteria is the only criteria that developed by a large international number of RLS clinical and research experts through an interdisciplinary, international and evidence-based approach which ensure it to be a world-wide consensus criteria which reduces the risk of cultural bias and avoids arbitrary and improve the validity. The specifiers for clinical course and significance are able to provide a method to define different target population which would help clinicians and researchers to offer better prevention and treatment strategies for specific groups of patients and to better elucidate etiopathogenesis (Allen et al., 2014).

On the other hand, some disadvantages still exist since the diagnostic criteria for RLS are subjective, some more objective and reliable diagnostic criteria need to be brought up for a further diagnosis and classification of RLS, such as biological markers, genetic features, PLMS measuring, polysomnography, and actigraphy changes. Some new tools are to be developed for standardize case ascertainment (Allen et al., 2014). A case-control study in Germany reveals that inositol metabolites increased specifically in RLS patients (Schulte et al., 2016). This might be a discovery approach using serum metabolite profiling in RLS.

Classification

The RLS includes two groups in general: primary RLS and secondary RLS.

Primary RLS is considered to be idiopathic when the cause is truly unknown. Among the idiopathic RLS, 40.9–92% of whom had a family history of RLS, indicating the important role of genetic factors in developing RLS (Winkelman et al., 1996; Winkelmann et al., 2002; Tison et al., 2005).

Most secondary RLS cases have an onset after 40 years old. Secondary RLS are those associated with a variety of neurological disorders, iron deficiency, pregnancy, or chronic renal failure (Winkelman et al., 1996; Curgunlu et al., 2012; Srivanitchapoom et al., 2014). A study in Turkey revealed that severity of RLS symptoms is very closely related to low ferritin level (Curgunlu et al. , 2012). In the earliest studies of RLS, some revealed that 25% of RLS patients have iron deficiency condition. The other correlated factors were diabetic peripheral neuropathy (Zobeiri and Shokoohi, 2014), painful neuropathies (Rutkove et al., 1996), ADHD (Roy et al., 2015), migraine (Zanigni et al., 2014), AS (Tekatas and Pamuk, 2015), leprosy (Padhi and Pradhan, 2014), inflammatory chronic demyelinating neuropathies like multiple sclerosis (Deriu et al., 2009) and Guillain–Barré syndrome (Marin et al., 2010), thyroid disease (Rodriguez Martin et al., 2015), poliomyelitis (Kumru et al., 2014), chronic venous disorder (McDonagh et al., 2007), autoimmune disease including Sjögren’s syndrome (Theander et al., 2010), rheumatoid arthritis (Hening and Caivano, 2008), inflammatory bowel disease (Becker et al., 2015), and Crohn’s disease (Hoek et al., 2015). Epidemiology studies also showed that the prevalence of RLS significantly increased in post-stroke patients, mainly in patients whose stroke topography lied on pyramidal tract and the basal ganglia-brainstem axis which were primarily involved in motor functions (Sechi and Sechi, 2013). Some certain drugs can cause or worsen RLS symptoms, such as psycotropics like antidepressants and neuroleptics, dopaminergic drugs, and some other drugs (Giudice, 2010) such as cumulative dopaminergic agonists effects in Parkinson’s disease patients (McDonagh et al., 2007). A study revealed that the strongest evidence for drug-induced RLS are for the following: escitalopram, fluoxetine, L-dopa/carbidopa and pergolide, L-thyroxine, mianserin, mirtazapine, olanzapine, and tramadol (Hoque and Chesson, 2010).

According to the onset age of the symptoms, RLS is divided into early-onset RLS and late-onset RLS. Early-onset RLS refers to those who firstly have the symptoms before 45 years old. While late-onset RLS patients have the symptoms from or after 45 years old. A higher familial history rate was found in early-onset RLS comparing to late-onset RLS (Kotagal and Silber, 2004). Various clinical courses with periodic remissions are common in early-onset RLS. While a chronic progressive clinical course with more severe symptoms are seen in late-onset RLS. Pediatric RLS are always misdiagnosed as “growing pain”. Current researches demonstrate a relatively iron deficiency and renal failure to be exacerbating factors for pediatric RLS (Kotagal and Silber, 2004; Davis et al., 2005; Applebee et al., 2009; Sinha et al., 2009). Commonly pediatric RLS should be differentiated from ADHD while only RLS patients presents the need to move because of leg discomfort but not difficulty “sitting still” (Trenkwalder et al., 2005).

Differential Diagnosis

Very common conditions which should be differentiated with RLS include leg cramps, positional discomfort, local leg injury, arthritis, leg edema, venous stasis, peripheral neuropathy, radiculopathy, habitual foot tapping/leg rocking, anxiety, myalgia, and drug-induced akathisia (Allen et al., 2014). They can mimic RLS in different ways. Leg cramps are presented as knot of the muscle. Positional discomfort can be relieved by a positional shift. Arthritis patients have a limitation of the joints or joint erythema. Myalgias present as muscle soreness. Numbness happen to neuropathy patients as well as RLS patients, and both venous stasis and leg edema can manifest as swelling in the limbs (Davis et al., 2005; Applebee et al., 2009; Sinha et al., 2009; Karroum et al., 2012). Less common differential diagnostic conditions included myelopathy, myopathy, vascular or neurogenic claudication, hypotensive akathisia, orthostatic tremor, painful legs, and moving toes (Allen et al., 2014). Differential diagnosis is really important to RLS patients for their further treatment. Therefore clinical physicians have created additional diagnostic questionnaires and scales to improve the diagnosis of RLS in clinical practice (Popat et al., 2010). RLS-NIH questionnaire, developed in 2002 with three mandatory questions, showed sensitivity and specificity of 86 and 45% respectively (Popat et al., 2010). On the basis of this, an the RLS-EXP showed the sensitivity and specificity of 81 and 73% respectively (Popat et al., 2010). The CH-RLSq is more commonly used in clinical practice and by researchers.

Secondary RLS

Iron Deficiency

Early in 1953, Nordlander (1953) first proposed that iron deficiency might be an important part of the pathophysiological process in RLS which was supported by consistent prevalence studies and recent pharmacological researches. Low serum iron levels (normal range: 50–170 μg/dL for men; 65–176 μg/dL for women; 50–120 μg/dL for children) presented in 25% of patients with severe RLS (Ekbom, 1960). While 43% of patients complaining of “leg restless” were found to be in the condition of iron deficiency (Matthews, 1976). The severity of the symptoms was found to be correlated with serum ferritin levels (normal range: 15–200 ng/mL for men; 12–150 ng/mL for women; 7–140 ng/mL for children) (O’Keeffe et al., 1994; Mizuno et al., 2005). Numbers of pharmacological studies of iron supplement for RLS gained therapeutic effects (Nordlander, 1953). CSF biological studies showed lower iron and ferritin levels in RLS patients, along with higher transferrin levels (Mizuno et al., 2005). However, a current study has suggested that in normal circumstances, the brain does not respond to peripheral variations in iron status (Ward et al., 2014). This might explain why some RLS patients had a normal or over-loaded serum iron level while their CSF iron level was decreased. Various medical imaging studies including ultrasound studies and MRI studies revealed a decreased iron levels in the substantia nigra and putamen, especially in the very severe patients (Schmidauer et al., 2005; Moon et al., 2014). Other studies demonstrated iron decrease in the red nucleus, thalamus and the pallidum (Haba-Rubio et al., 2005; Rizzo et al., 2013). However, MRI was not capable of locating the iron deficiency condition to particular cells up to now. Autopsy studies also reported a decrease in iron concentration in the substantia nigra (Moon et al., 2014).

Pregnancy

15–25% of pregnant women have RLS in Western countries according to prevalence studies (Lee et al., 2001; Neau et al., 2010). A peak prevalence of RLS in pregnant women mainly occurred in the third trimester and gained a remission by 1 month after delivery (Ismailogullari et al., 2010). Surveys manifested that nulliparous women were at the same risk of RLS as same aged men, while the risk for women were increased after one pregnancy (OR 1.98) and two pregnancies (OR 3.04), even more after three or more pregnancies (OR 3.57) (Berger et al., 2004; Pantaleo et al., 2010). These findings may explain the gender difference in RLS prevalence. The reason why pregnant women have higher risk of having RLS remains unknown. One reason is that an increased demand of iron in pregnant women results in relative iron deficiency. The other established factors included hormonal status (prolactin, progesterone and estrogen), folate deficiency and stretch or compression of nerves due to fetal growth conflicting (Pantaleo et al., 2010; Pereira et al., 2013). Psychomotor behavioral change during the last weeks of pregnancy might also contribute to the symptoms. Anxiety, insomnia, and fatigue are always associated with pregnancy in the last trimester.

End-Stage Renal Disease Patients on Hemodialysis

Studies have revealed approximate prevalence of 20–30% RLS in hemodialysis than the prevalence of 3.9–15% among the general populations (Ohayon et al., 2012). A study including 166 patients in Serbian showed 22.7% of patients on hemodialysis were under the condition of RLS (Nikic et al., 2007). Other studies indicated a prevalence of 14.8% among 176 patients on hemodialysis in Brazil (Goffredo Filho et al., 2003) and a prevalence of 37.4% in 163 patients on hemodialysis in Iran (Rohani et al., 2015). Some of the studies revealed a predominance of female patients with RLS rather than male patients on hemodialysis (Al-Jahdali et al., 2009; La Manna et al., 2011; Haider et al., 2014), while a recent study in Saudi displayed no statistically difference between two genders (Wali and Alkhouli, 2015). Most of the RLS patients among end-stage renal disease indicated moderate to severe symptoms compared to most mild RLS symptoms among general populations (Wali and Alkhouli, 2015). Iron deficiency in end-stage renal disease patients may lead to anemia and affect the dopamine metabolism, contributing to RLS (Nikic et al., 2007), and uremia-related peripheral neuropathy and high serum calcium can be part of the physiology of RLS (Nikic et al., 2007). However, in a recent report, iron deficiency, anemia, and calcium were not found to be statistically related to RLS in hemodialysis patients (Wali and Alkhouli, 2015). Previous studies showed conflicts about the association between BMI and RLS in end-stage renal disease patients. A study with a large cohort found that the prevalence of RLS in end-stage renal disease patients was positively related to their BMI (Gao et al., 2009). The OR for RLS was 1.42 (95% CI: 1.3–1.6; p < 0.0001) for patients with BMI from 23 to 30 kg/m² and 1.60 (95% CI: 1.5–1.8; p < 0.0001) for patients with highest BMI compared with patients with lowest BMI (Gao et al., 2009). Decreased number of dopamine receptors in obese people’s brain was considered to be the possible reason (Wang et al., 2001). However, another previous study revealed no such relationships (Kim et al., 2008). A recent cross-sectional study between control group, renal transplantation group and hemodialysis group found that prevalence in renal transplantation is significantly lower than in hemodialysis patients (Kahvecioglu et al., 2016). RLS is very prevalent in end-stage renal disease patients, and hemodialysis patients with RLS were found to have a higher risk of muscle atrophy (Giannaki et al., 2011), cardio/cerebrovascular events and mortality (Lin C.H. et al., 2015). To prevent more morbidity in end-stage renal disease patients, their RLS should be diagnosed in early stage and receive standard treatment of RLS or have a renal transplantation as soon as possible.

Pathophysiology

The pathophysiology of RLS is still partially understood. The most accepted pathways include genetics variants, abnormal iron metabolisms, dopaminergic dysfunction, and central opiate system.

Iron

It’s widely accepted that the local brain iron level plays an important role in RLS pathophysiology, however, the mechanism is still unclear. Recent studies demonstrated that the iron deficiency in brain was related to the function of blood-brain interface, as BBBs endothelial cells acted as an iron reservoir for the brain. A dysfunction of iron regulatory protein in the microvasculature incited dysregulation of iron transport across the BBB, resulting in a decrease of iron storage in endothelial cells (Lee et al., 2001). Biochemical studies on the effect of iron in brain indicated that several proteins containing iron were included in various processes like oxidative phosphorylation, oxygen transportation, myelin production and the synthesis and metabolism of neurotransmitters (Ward et al., 2014). Therefore, iron deficiency can lead to cellular damage by oxidation and modification of cellular compounds such as lipids, carbohydrates, protein, and DNA from hydroxyl radical production (Ward et al., 2014). The interactions between impaired neuronal iron uptake and the functions of the neuromelanin-containing and dopamine-producing cells play important roles in RLS pathophysiology (Michaud et al., 2004). Decreased extracellular dopamine, DAT, D1 and D2 receptors are found in iron deficiency, indicating that iron affect the brain dopaminergic transmission in different ways (Dauvilliers and Winkelmann, 2013).

Dopamine

A large number of pharmacological studies and clinical findings have provided evidence for the important role of dopaminergic system dysfunction in RLS (Winkelmann et al., 2001; Paulus and Trenkwalder, 2006; Galbiati et al., 2015). An improvement of RLS symptoms was found in patients receiving low-dose dopaminergic medications (Paulus and Trenkwalder, 2006; Galbiati et al., 2015) while a worsening of RLS symptoms in patients receiving dopamine antagonists (Winkelmann et al., 2001). The need for dopaminergic agonists to cross the BBB to be effective in RLS symptoms indicated that dopaminergic system in central nervous system was entailed in RLS pathophysiology rather than in peripheral nervous system (Garcia-Borreguero and Williams, 2014). Tyrosine hydroxylase is a rate-limiting step enzyme for the conversion of levodopa to dopamine. As iron is a cofactor of this enzyme, iron deficiency can alter the dopaminergic system in the brain (Dauvilliers and Winkelmann, 2013). Dopaminergic A11 cells, located in the midbrain and close to hypothalamus, have long axons and project diffusely throughout the spinal cord (Clemens and Hochman, 2004). They are the major source of dopamine in spinal cord. A11 cells arrive in the dorsal horn, then project to the motoneuronal site (Holstege et al., 1996). It’s found that stereotaxic bilateral 6-hydroxydopamine lesions into the A11 nucleus can result in an increased average number of standing episodes and total standing time comparing to the sham rats (Ondo et al., 2000), suggesting an important role of A11 dopaminergic cells in pathophysiological pathways in RLS. A significantly decreased N-acetylaspartate, creatinine ratio, and N-acetylaspartate concentrations were found in the medial thalamus of RLS patients in a recent study using proton magnetic resonance spectroscopy (Rizzo et al., 2012). Functional MRI and PET studies concluded an important role of medial thalamic nuclei in RLS pathophysiology. The medial thalamic nuclei are part of the limbic system, which is modulated by dopaminergic afferents. Another study found thalamic activity changes in the thalamocotrical circuit (Goulart et al., 2014). Therefore, it was hypothesized that the dopaminergic dysfunction might lead to an impairment of the medial pain system (Garcia-Borreguero and Williams, 2014; Goulart et al., 2014) and then caused the uncomfortable symptoms of RLS. Pharmacological studies also demonstrated that opioids had a protective effect in some RLS patients. An in vitro study in rats found that iron deficiency can cause cell death, mainly dopaminergic cells in substantia nigra and opioids could protect them from cell death under the condition of iron deprivation (Sun et al., 2011). The authors concluded from this result that an intact endogenous opioid system and opioid treatment could prevent the dopamine system from dysfunction in iron deficiency patients (Sun et al., 2011). A study of tsDCS in RLS patients showed supportive evidence of spinal cord hyperexcitability (Heide et al., 2014).

Genes

Studies demonstrate a strong relationship between genetic predisposition and early-onset RLS, of which more than 60% reveal a positive familial history. Moreover, inheritance was found to be related to late-onset RLS and secondary RLS (Winkelmann et al., 2000; Xiong et al., 2010; Yang et al., 2011). A study among 249 Canadian RLS patients found a family history existed in 77.1% of them while the rest 22.9% were sporadic (Yang et al., 2011). Variants in MEIS1, BTBD9 and MAP2K5/SKOR1 resulted in a much higher risk of RLS among a US population (Yang et al., 2011). So far, the GWASs have reported the following susceptible SNPs in association with RLS: MEIS1 (chromosome 2p14), BTBD9 (chromosome 6p21.2), PTPRD (chromosome 9p24.1-p23), MAP2K5/SCOR1 (chromosome 15q23) and chromosome 16q12.1 (Berger et al., 2002; Hogl et al., 2005; Stefansson et al., 2007; Schormair et al., 2008). Main function of these genes was related to embryonic neuronal development and limb development (Dauvilliers and Winkelmann, 2013; Garcia-Borreguero and Williams, 2014). In RLS autopsy cases, MEIS1 gene was found to be associated with an increase in H-ferritin, L-ferritin and divalent metal transporter-1 RNA expression in the thalamus (Catoire et al., 2011), suggesting MEIS1 gene mutants predisposed to lower iron condition. Another study used RNA interference techniques in a lymphoblastoid cell line in which the MEIS mRNA expression was blocked (Silver et al., 2010). Forty-eight hours later, an increase in transferring-2 receptor, ferroportin mRNA and BTBD9, and a decrease in hepcidin mRNA expression were observed (Silver et al., 2010), indicating that MEIS1 controlled cellular iron transfer to mitochondria, cellular export of iron and potentially affected BTBD9 expression and its downstream iron modulation. The effect of MEIS1 on iron homeostasis was also shown in Caenorhabditis elegans (Catoire et al., 2011). A study using dBTBD9 mutant flies showed significantly decreased brain dopamine and abnormal sleep phenotype which was completely retrieved by administering with pramipexole, a dopamine D2 receptor agonist (Freeman et al., 2012). Furthermore, RLS symptoms can be reconstructed by knocking-down dBTBD9 expression. While over expression of BTBD9 in HEK cells showed that the gene controlled iron homeostasis through the regulation of IRP2 (Freeman et al., 2012). The authors suggested that the BTBD9 protein belonged to a protein family which contained substrate adaptors for the Cul3 class (Freeman et al., 2012). Cul3 class of E3 ubiquitin ligases was shown to regulate sleep in flies (Stavropoulos and Young, 2011). A susceptible view point was that BTBD9 played a role in dopamine biosynthesis by unclear mechanisms (Shaw and Duntley, 2012). These SNPs had strong association with PLM in RLS patients (Moore et al., 2014). The exact pathophysiological pathways of these genes still remain unclear. An SNP study in the Spanish Caucasian population suggested a modest but significant association between vitamin D receptor rs731236 SNP and the risk for RLS. RLS patients carrying the allelic variant rs731236G had an earlier onset age while those carrying the allelic variant rs731236GG had more severe symptoms (Jimenez-Jimenez et al., 2015). A weak association between heme oxygenase genetic variants HMOX1 rs2071746 polymorphism and the risk of developing RLS was found in the Spanish population (Garcia-Martin et al., 2015). Linkage analyses in families identified several genetic loci for RLS: RLS1 (chromosome 12q12–q21), RLS2 (14q13–q21), RLS3 (9p24–p22), RLS4 (2q33), RLS5 (20p13), RLS6 (19p13), and RLS7 (16p12.1) (Desautels et al., 2001, 2005; Bonati et al., 2003; Kemlink et al., 2007). The authors suggested the inheritance mode of RLS could be a recessive mode or a dominant mode with variable of inheritance. The main SNP findings are summarized as below (Table 3).

TABLE 3. Main SNP findings associated with RLS.

Nervous System Structures

Previous theories about dopaminergic effect on RLS pathophysiology mainly focused on substantia nigra and dopaminergic A11 cell group (Ondo et al., 2000; Trenkwalder and Paulus, 2010), nevertheless, changes in dopaminergic neurons in basal ganglia in RLS patients were also found in autopsy studies. This result might be related to iron deficiency in brain (Connor et al., 2003). Dopaminergic projections to the spinal cord originate exclusively from A11 cell group (Noga et al., 2004). Dopamine acted as an excitatory and inhibitory neurotransmitter in spinal cord to regulate sensory, motor as well as autonomic functions (Dauvilliers and Winkelmann, 2013). Recent studies reported frequent PLMS in patients with spinal cord injury, indicating the center role of spinal cord in RLS pathophysiology process (Dauvilliers and Winkelmann, 2013). It might also result from the decreasing supraspinal inhibition to the spinal cord. Functional MRI studies showed changes of thalamic and cerebral activation in RLS (Bucher et al., 1997). However, postmortem studies in RLS patients showed no evidence of changes in the volume of tyrosine kinase (+) neurons or gliosis changes in A11 region in the posterior hypothalamus (Earley et al., 2009). This might result from the fact that only six cases are included in this study or the hypothesis that the manifestations of RLS may be secondary to dopamine metabolism or changes in the distal A11 synapses which is not as easily detected as structural or quantity changes in the cell bodies (Earley et al., 2009). Another recent study indicated that domperidone, a dopamine antagonist that cannot cross the BBB increased the frequency of RLS in patients with Parkinson’s Disease, proposing that peripheral dopaminergic neurons might play an important role in RLS (Rios Romenets et al., 2013). It’s widely believed that iron deficiency in brain causes the decrease in dopaminergic function which then motivates spinal hyperexcitability, leading to the spontaneous sensory and motor movements of RLS (Garcia-Borreguero and Williams, 2014).

Treatment

Treatment before RLS, three aspects should be considered: lifestyle change, medication effect and iron deficiency (defined as ferritin < 75 ng/mL or iron/TIBC ratio < 20%) (Mackie and Winkelman, 2015). Lifestyle like sleep deprivation, alcohol or tobacco use, decreased motility, or in medication (dopamine antagonists, antihistamines or serotonergic antidepressants, opioid discontinuation or blood loss) can result in earlier onset or increase severity in RLS symptoms. A detailed inquiry for the patient should be carried out. Treatment of RLS mainly include pharmacological and non-pharmacological treatment.

Pharmacological Treatment

Dopaminergic agents are considered to be the first-line treatment for RLS, including pramipexole and ropinirole (Garcia-Borreguero et al., 2013; Silber et al., 2013). Pergolide and cabergoline are not recommended due to their association with increased risk of valvular heart disease (Zanettini et al., 2007). Ropinirole has a faster onset with shorter duration, while rotigotine is commonly used as a transdermal patch which continuously provides stable plasma drug concentrations, resulting in its particular therapeutic effect on patients with symptoms throughout the day (Mackie and Winkelman, 2015). α2δ agonists have become increasingly important in treating RLS, for being considered as possible first-line agents for RLS. A recent double-blind study over 12-week period compared the efficacy of pregabalin, pramipexole and placebo, demonstrating a better efficacy of pregabalin rather than dopamine agonist or placebo (Hubner et al., 2013). Moreover, the difference of the efficacy varied with drug doses (Hubner et al., 2013). Opioids have been found to be effective in treating RLS, but the potential drug abuse and side effects including respiratory depression and constipation limit its use in RLS, as they are not commonly advised as initial treatment of choice. A recent study on treating first-line agents refractory RLS with extended-release oxycodone–naloxone combination showed very impressive and persistent effect of this combination on RLS symptoms (Trenkwalder et al., 2013). Other pharmacological treatments include iron supplement, some other anticonvulsants and benzodiazepines. The choice of two major first-line agents should be considered with their side effects. Dopamine agonists can cause somnolence and ICDs like compulsive gambling or over-eating, while common side effects of α2δ agonists are weight gain, dizziness and gait instability. As a result, for initial treatment of RLS patients, dopaminergic agents are used as first-line agents in patients with very severe symptoms, over-weighted, comorbid depression, risk of falls, or cognitive impairment (Garcia-Borreguero et al., 2013), while α2δ agonists are advised as first-line agents in patients with severe sleep disturbance, comorbid anxiety, RLS-related pain, or previous history of ICDs (Garcia-Borreguero et al., 2013). Evidence-based guidelines on treating RLS were published by EFNS and IRLSSG in 2012 and 2013 respectively. Many other pharmacological treatment reviews and research papers of RLS have been published recently (Garcia-Borreguero and Williams, 2014; Hornyak et al., 2014). A conclusion of several medications is shown above (Table 4).

TABLE 4. Recommendation drugs for RLS.

Other drugs such as dopaminergic agents (piribedil), anticonvulsants (gabapentin), opioids (tramadol, methodone), iron, hypnotic and sedative agents, folate, vitamin B₁₂, magnesium, vitamin E, botulinum toxin, physiotherapy, phototherapy, and aerobic exercises are not recommended in clinical practice due to insufficient evidence. However, they can be used as auxiliary drugs concerning to the symptoms and comorbidities of the patient.

As depression is a very common comorbidity in RLS and many antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) can worsen the symptoms of RLS, treatment of depression in RLS patients should be cautious. Since bupropion, a newer antidepressant, doesn’t show any evidence of exacerbation of RLS symptoms, it is used as an effective antidepressant in these patients (Mackie and Winkelman, 2015).

Restless legs syndrome is very common in women during pregnancy and lactation, with a prevalence of 15–25% (Hubner et al., 2013). Guidelines on treating RLS during pregnancy and lactation have been published by IRLSSG in 2014 (Picchietti et al., 2015) (Table 5). Once RLS is diagnosed in pregnancy, non-medicine treatment should be considered firstly. Patients should be educated about the natural course of RLS during pregnancy, in which RLS commonly remits or disappears after delivery. Moderate exercise and avoidance of aggravated factors such as iron deficiency, long-term immobility, serotonergic antidepressants should be suggested. Iron level should be measured to decide whether to treat the patient with iron. Iron therapy (oral or intravenous) should be given when serum ferritin < 75 ug/L. When serum ferritin > 75 ug/L with refractory RLS, drug treatment should be considered.

TABLE 5. Medication treatment for RLS in women during pregnancy and lactation.

Loss of efficacy and augmentation are two main treatment failures after a long course of treatment of RLS. The probable reasons of them might be the natural worsening of RLS symptoms over time or compensatory response of CNS to chronic drug treatment (Mackie and Winkelman, 2015). Iron deficiency should be treated with iron supplement. Both of the intravenous and oral iron formulations are proved to be effective in some RLS patients (Trotti et al., 2012; Hornyak et al., 2014). Further study about effect of iron therapy in all RLS patients or only a certain type of RLS remains to be investigated.

Augmentation refers to a worsening of the symptoms that occurs very commonly among RLS patients after long-term treatment with some certain medications. An overall augmentation rate of 5.6% was reported (Liu et al., 2016). All the current dopaminergic drugs and another non-dopaminergic drug tramadol have been reported to show some degree of augmentation (Trenkwalder et al., 2007; Vetrugno et al., 2007; Hogl et al., 2010; Oertel et al., 2011), which are thought to be related to dose and duration of medication and individual factors such as iron deficiency (Garcia-Borreguero et al., 2013). The highest incidence rate of augmentation occurred with levodopa was up to 60–80% in RLS patients (Hogl et al., 2010). In addition, incidence rate was reported to be higher in patients treating with shorter-acting dopaminergic agents (pramipexole, ropinirole) than longer-acting dopaminergic agents (rotigotine, cabergoling). A possible explanation is the masking of earlier symptom onset by longer-acting dopaminergic agents (Garcia-Borreguero and Williams, 2014). To prevent augmentation, it is important to initiate the treatment with α2δ agonists for milder RLS patients (Silber et al., 2013), and a lowest effective dose of dopaminergic agents should be established to decrease the incidence and delay the occurrence of augmentation (Silber et al., 2013). Management of augmentation is not to increase the dose of dopaminergic agents, but to add a non-dopaminergic agent as a combination strategy (Silber et al., 2013). Moreover, loss of efficacy is the reduction of drug efficacy over time. In these cases, RLS symptoms are not worse than before initiating the treatment (Garcia-Borreguero and Williams, 2014), a combination therapy is recommended in loss of efficacy to decrease the side effects of certain medications, as well as to prevent augmentation.

Non-pharmacological Treatment

Sleep hygiene should be corrected before all the pharmacological treatment. Sleep deprivation, sleep disturbances and factors that can result in insomnia should all be avoided. Another common but easily neglected disorder is OSAS. Early treatment for OSAS is beneficial for improving sleep for RLS patients. Other non-pharmacological treatments have been proven to be effective in RLS. tsDCS showed a short-lasting clinical improvement in idiopathic RLS patients (Heide et al., 2014), while high-frequency rTMS resulted in an significant improvement in the motor symptoms and sleep disturbances in RLS patients (Lin Y.C. et al., 2015). But these non-pharmacological treatment for RLS studies are scarce. They show some advantages in symptomatic RLS patients who do not respond to or do not tolerate the classic pharmacological treatments. It may bring brand new solutions to these patients. On the other hand, these methods are non-invasive and safe, no significant side effects have been observed yet. Developing these new methods can be a great benefit for RLS patients.

Conclusion

There have been a lot of advances in the fields of RLS in recent years, as the diagnostic criteria have been revised in 2012. A deeper insight in pathophysiology of RLS has put iron metabolism dysfunction in an important position, as well as dopaminergic system dysfunction, has been demonstrated. Guidelines of long-term treatment of RLS are published by IRLSSG in 2013 to help with the treatment of RLS for clinicians. Prevention and management of augmentation for long-term treatment has been improved through clinical experience and researches. More researches should be done to discover the pathophysiology, and to find better treatment and management of augmentation of RLS.

Author Contributions

SG: drafting the manuscript and the tables; HJ, CH, JL, XX, GZ: giving advice on conception and design; JH, NX: revising the manuscript; ZL: giving advice on conception and design; TW: conception and design. Giving final approval of the version to be published.

Funding

This work was supported by grants 31171211 and 81471305 from the National Natural Science Foundation of China (to TW), grant 81200983 from the National Natural Science Foundation of China (to NX), grant 81301082 from the National Natural Science Foundation of China (to JH), grant 2012B09 from China Medical Foundation (to NX) and grant 0203201343 from Hubei Molecular Imaging Key Laboratory (to NX).

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Abbreviations

ADHD, attention-deficit/hyperactivity disorder; AS, ankylosing spondylitis; BBBs, blood–brain barriers; CH-RLSq, Cambridge–Hopkins diagnostic questionnaire for RLS; CI, confidence interval; CSF, cerebrospinal fluid; Cul3, Cullin-3; DA, dopaminergic; DAT, dopamine transporter; DCSAD, Diagnostic Classification of Sleep and Arousal Disorders; DIMS, disorder of initiating and maintaining sleep; DOES, disorder of excessive somnolence; EFNS, European Federation of Neurological Societies; EXP, expanded screening questionnaire; GWASs, genome-wide association studies; HRQoL, health-related quality of life; ICDs, impulse control disorders; ICSD, International Classification of Sleep Disorders; IRLS, international restless legs scale; IRLSSG, International Restless Legs Syndrome Study Group; IRP2, iron regulatory protein-2; NIH, National Institutes of Health; OR, odd ratio; OSAS, obstructive sleep apnea syndrome; PLMs, periodic limb movements; PLMS, periodic limb movement during sleep; PLMW, periodic limb movement during wakefulness; PSG, polysomnogram; RLS, restless legs syndrome; rTMS, repetitive transcranial magnetic stimulation; SNPs, single nucleotide polymorphisms; tsDCS, transcutaneous spinal direct current stimulation.

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Tips to lessen Restless Leg Syndrome symptoms | ABC7 New York | abc7ny.com

NEW YORK

Restless leg is a condition that can lead to poor sleep and daytime drowsiness.

Twitching legs, a shock shooting down the legs. That’s how one sufferer described Restless Leg Syndrome. Moving makes it better, but if those movements happen in the middle of the night, the result can be poor sleep. Research recently showed that it runs in families, as it does for Chris Cook.

Holding hands, Chris and Karen cook seem like a happy couple, and they are, but Chris kicks his wife at night.

“She’s been awakened in the middle of the night because I’ve been asleep and my legs have been kicking,” Chris said.

Chris has Restless Leg Syndrome, or RLS and he’s not even aware it’s happening, except as he gets into bed and relaxes.

“It’s like an electric shock and your body goes like that, and there’s nothing you can do to stop it,” Chris said.

Symptoms can be worse in the heat and at the end of the day. RLS is twice as common in women as in men, and can come along with diabetes, thyroid problems, and varicose veins. Pregnant women can get it, especially if they’re deficient in iron. Chris’ grandmother and cousins have RLS, and new studies show that, indeed, it’s genetic.

“We don’t know why it happens but it’s a circadian rhythm thing, it follows a 24 hour clock and may be related to melatonin,” said Dr. Ana Krieger from NR Pres Weill Cornell.

RLS can be a cause of insomnia. Moreover, multiple awakenings means a poor night’s sleep.

Sufferers can sleep soundly with treatment.

Increasing the brain chemical dopamine can help RLS. The medications for RLS act like an artificial dopamine to reduce leg movement.

There are a couple of prescription drugs that work like dopamine. And there are some tips to reduce the problem and insomnia in general.

Avoid or limit alcohol, caffeine and nicotine stimulants. Avoid heavy meals close to bedtime. Keep a regular sleep schedule and wake up at the same time each day.

Chris was doing well on one medication until the past few weeks. A probable cause could be the hot weather. But increasing the dose did the trick.

“Last night was the first night and I slept like a baby,” Chris said.

Chris says that getting up and walking around can reduce the symptoms, but this can only add to the problem of getting sleep. About 75 to 80 percent of sufferers respond to the medications. Too much medication may make symptoms worse and can set them off earlier in the day.

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Can Magnesium Supplements Really Help You Sleep?

Magnesium is often touted as an antidote to poor sleep. But while some doctors say it is fine to take it in supplemental form for certain sleep disruptions, like those caused by restless legs syndrome, the evidence for its sleep-inducing benefits is thin.

Magnesium, an abundant mineral in the body, plays a critical role in many physiological functions. It helps support immune health, blood sugar regulation, and nerve and muscle function. Some scientists suspect that magnesium deficiencies can contribute to poor sleep by disrupting nerve signaling and altering levels of sleep-inducing hormones such as melatonin.

But most people have sufficient levels of magnesium, since the mineral is easy to get if you follow a relatively healthy diet. It’s found in a variety of plant and animal foods like nuts, greens, seeds, beans, yogurt and fish. And although many people fall short of the federal government’s recommended daily intake, true magnesium deficiencies are rare.

Over the years, studies have looked at whether supplementing with the mineral can improve sleep. Most of the studies have been small or poorly designed, making it difficult to draw firm conclusions. One systematic review published in April looked at three clinical trials that studied magnesium supplementation for insomnia in 151 older adults and concluded that they generally provided “low to very low quality of evidence.”

In one study published in 2012, researchers recruited 46 older adults with chronic insomnia and split them into two groups. One was assigned to take 500 milligrams of magnesium every day for eight weeks, and the other was given placebo. At the end of the study, the researchers found that compared with the placebo group, the people taking magnesium were more likely to report improvements in “subjective” measures of insomnia, such as how quickly they fell asleep each night and the number of times they reported waking up in the early morning hours. But those taking magnesium did not show any difference in their total sleep time, the researchers reported.

In general, magnesium seems to have minimal side effects, and taking low doses is unlikely to cause much harm. According to the Institute of Medicine, healthy adults can safely take up to 350 milligrams of supplemental magnesium daily. Anything at or below that level is unlikely to cause any adverse health effects. But at higher doses, magnesium can cause gastrointestinal issues like diarrhea, said Dr. Colleen Lance, the medical director for the Sleep Disorders Center at Cleveland Clinic Hillcrest Hospital in Ohio. Dr. Lance said that while the evidence that magnesium can help with insomnia is weak, she does not necessarily discourage people from trying it.

“I tell patients you can give it a try and see if it helps,” she said. “It may not help, but it’s probably not going to hurt.”

Tips for Better Sleep

Tired of tossing and turning? There are some strategies you could try to improve your hours in bed.

One instance where she does recommend magnesium is for patients who have restless legs syndrome, a nervous system disorder that causes people to have irresistible urges to move their limbs, usually at night, which can be highly disruptive to sleep. Dr. Lance said that magnesium could, in theory, make a difference because it helps nerves properly relay electrical signals, though evidence of its benefits for restless legs is still limited and mixed, and it may not work for everyone.

At least one small study from 1998 found that people who had the disorder had fewer sleep disruptions after taking magnesium. However, a more recent systematic review of studies concluded that it was “not clear” whether magnesium could alleviate restless legs syndrome. More research is needed, but Dr. Lance said that she tells patients with R.L.S. that it may be worth trying to see if it makes any difference. “We tell patients that they can try some magnesium in the evening hours to see if that calms things down,” Dr. Lance added.

Chronic insomnia, however, is not usually something that can be fixed with a pill. When Dr. Lance meets patients who complain of insomnia, she typically does an evaluation to figure out the root causes of their sleepless nights. Often, she finds that a patient might be having trouble falling or staying asleep because of an undiagnosed sleep disorder, like sleep apnea or restless legs syndrome. Many women have sleep problems related to menopause. Some people cannot sleep soundly because their environment is too noisy — they could have a spouse who snores, for example, or a dog that barks through the night. Others may be struggling to sleep because of anxiety related to the pandemic, their work, their finances or some other stressful situation in their lives.

One of the most effective treatments for insomnia is cognitive behavioral therapy, or C.B.T., which helps people address the underlying behaviors that are disrupting their sleep. Therapies like continuous positive airway pressure, or CPAP, can help people with sleep apnea. Medications, including supplements like melatonin, may also be helpful in some cases, but a pill alone is not going to cure insomnia, Dr. Lance said.

“We see a lot of people who have some underlying issue and yet they’re looking for a pill to sleep through the problem,” she said. “Whereas what we try to do instead is find and address the underlying problem.”

Restless legs syndrome – reasons, how to win, treatment in Kiev

What is restless legs syndrome?

Restless legs syndrome is a neurological sleep disorder that makes you feel uncomfortable and want to move your legs. Restless legs syndrome prevents you from falling asleep normally. Symptoms are usually worse in the evening and at night. The feeling is hard to describe to some people. You may lie down and start feeling itchy inside legs. These symptoms may disappear. The discomfort may return when you try to fall asleep again.

In some cases of restless legs syndrome, you have trouble sitting still for a long time. Long journeys by car or plane can be difficult.

Many people wait years to seek treatment because they do not see it as a serious problem. You may notice that your symptoms become more frequent and more severe.

Restless Legs Syndrome can make you stay awake every night. Many people with severe cases sleep less than five hours a night.Mild cases do not disturb your sleep as much, although sleep may be of lower quality.

Accumulated sleep loss from restless legs syndrome can cause irritation and make it difficult to concentrate. This can have a serious impact on your professional and personal life. People with restless legs syndrome are more likely to suffer from depression or anxiety.

Restless legs syndrome is usually treatable with medication and lifestyle changes.

Restless legs syndrome develops after age 45 for most people, although it can develop at any age.Women are almost twice as likely to develop this disorder as men. If you have a family member with restless legs syndrome, you are more likely to develop symptoms before you turn 45. More than half of people with restless legs syndrome also have family members with the same problems, since the likelihood of a similar situation is 3-6 times higher.

Overview of Restless Legs Syndrome

Restless Legs Syndrome (RLS) is a condition that causes an uncontrollable urge to move your legs, usually due to discomfort.This usually happens in the evening or at night when you are sitting or lying down. Moving temporarily relieves discomfort.

Restless legs syndrome, also known as Willis-Ekbom disease , can start at any age and usually gets worse with age. It can disrupt sleep, interfering with daily activities.

Simple self-care and lifestyle changes can help relieve symptoms. Medication also works for many people with RLS.

Symptoms of restless legs syndrome

The main symptom is the urge to move your legs. Common related characteristics of RLS include:

• Feelings that begin after rest. The sensation usually begins after lying or sitting for a long time, for example, in a car, plane or movie theater.
• Movement relief. The sensation of RLS decreases with movement such as stretching, swinging the legs, or walking.
• Exacerbation of symptoms in the evening. Symptoms occur mainly at night.
• Leg twitching at night. RLS may be associated with another, more common condition called intermittent limb movement during sleep, which causes your legs to twitch and push, possibly during the night while you are asleep.

People commonly describe RLS symptoms as abnormal, uncomfortable sensations in the legs or feet. They usually appear on both sides of the body.Less commonly, the sensations affect the hands.

Feelings that usually occur in the limbs and not on the skin are described as:

• Crawling sensations
• Pulling sensations
• Pulsation
• Aching pain
• Itching
• Feels like electricity

cause pain, but can cause discomfort and psychosomatic disorders.

Sometimes these feelings are difficult to explain.People with RLS do not usually describe the condition as muscle spasm or numbness. They do, however, consistently describe the urge to move the legs.

Symptoms usually vary in severity. Sometimes the symptoms disappear for a while and then return. The syndrome can have sensory manifestations (direct signs of the disease) and psychosomatic (consequences of the disease).

The psychosomatics of restless legs syndrome can be in the form of depressive conditions that occur due to regular lack of sleep.Symptoms can be aggravated by exposure to stress in public places or in their place of work.

When should I see a doctor?

Some people with RLS never seek medical attention because they worry they will not be taken seriously. But RLS can affect your sleep and cause daytime sleepiness and affect your quality of life. Talk to your doctor if you think you may have RLS.

Causes of Restless Legs Syndrome

There is often no known cause for RLS.Researchers suspect this condition may be caused by an imbalance in the chemical dopamine in the brain, which sends messages to control muscle movement.

Heredity

Sometimes RLS can occur in members of the same family, especially if the condition manifests itself before the age of 40. Researchers have identified regions on chromosomes where genes for RLS may be present.

Pregnancy

Pregnancy or hormonal changes may temporarily worsen the signs and symptoms of RLS.Some women develop RLS for the first time during pregnancy, especially during their last trimester. However, symptoms usually resolve after childbirth.

Risk factors

RLS can develop at any age, even during childhood. The disorder is more common with age and is more common in women than in men.

RLS is not usually associated with a serious medical problem. However, this syndrome sometimes occurs in conjunction with other conditions such as:

• Peripheral neuropathy. This damage to the nerves in your hands and feet is sometimes associated with chronic medical conditions such as diabetes and alcoholism.
• Iron deficiency. Even without anemia, iron deficiency can cause or worsen RLS. If you have a history of stomach or intestinal bleeding, have heavy menstrual periods, or donate blood repeatedly, you may be iron deficient.
• Renal failure. If you have kidney failure, you may also have iron deficiency, often with anemia.When the kidneys are not functioning properly, iron stores in the blood can decrease. This and other changes in body chemistry can cause or worsen RLS.
• Spinal cord condition. Spinal cord injury from injury or trauma has been associated with RLS. Having anesthesia in the spinal cord, such as a spinal block, also increases the risk of developing RLS.

Complications of Restless Legs Syndrome

Although RLS does not lead to other serious conditions, symptoms can range from mildly bothersome to disabling.Many people with RLS have difficulty falling asleep or sleeping.

Severe RLS can cause a marked deterioration in quality of life and lead to depression. Insomnia can lead to excessive daytime sleepiness, but RLS may prevent you from taking a nap.

How is restless legs syndrome diagnosed?

Self-Test

• Are you having difficulty falling asleep because of the urge to move your legs?
• Do you wake up at night because your feet are on fire?
• Do you feel itchy legs when you go to bed?
• Do your legs seem to feel better when you walk, stretch, or do other movements?

If you answered yes to any of these questions, you may have restless legs syndrome.

Diagnosis

Talk to your sleep doctor if you think you have restless legs syndrome. The doctor will ask you about your medical history and if you are taking any medications.

The sleep doctor may ask you to keep a sleep diary for two weeks to show you when you sleep and for how long. You can also assess how sleep affects your daily life using a simple questionnaire. Be sure to tell your doctor if you or a relative has ever had a sleep disorder.

Your sleep doctor may order blood tests, including iron measurements.

In some cases, he may recommend a sleep study. Sleep research can be used to make sure you do not have sleep apnea or other sleep disorders that can cause sleep disturbance. This is useful, but not required for the diagnosis of restless legs syndrome.

Gone Into the Night All over the world people suffer from restless sleep. Technologies came to their aid: People: From life: Lenta.Common crawl en

As childhood shapes adulthood, so night sleep is the next day. Therefore, it is extremely important to approach it responsibly, to sleep correctly and fully, that is, eight hours. Today, technology has penetrated widely into everyday life, and if in the case of wakefulness this is not always good, then technologies for sleep often have a positive effect. “Lenta.ru” and “Beeline” tell you how to stop snoring, have vivid dreams and get enough sleep.

The University of Colorado’s animal husbandry doctor Temple Grandin has a minimum of stuff in his bedroom: a bed, a chair, and a crimper.It is designed so that a person can at any time receive the hug he lacks, feel protected and calm. Grandeen invented this machine because she always wanted hugs, but she had difficulty getting in touch with people.

The idea was adopted by psychotherapists who helped patients by making their blankets heavier in various ways so that people would feel good in their sleep. Not so long ago, such blankets hit mass production – now everyone can purchase a heavy blanket.

It weighs from seven to 14 kilograms. The pressure on the body produces serotonin, a mood-boosting hormone, and melatonin, which helps you fall asleep.

Over the past ten years, there have been two major studies that have confirmed the effectiveness of these blankets. They are published in the scientific journals Occupational Therapy in Mental Health and Australasian Psychiatry. You can pre-order a Gravity brand blanket, for example, here at Madrobots *.

There are many types of headphones and devices that help you fall asleep using different sounds.The easiest and cheapest way is to install a special application on a smartphone, but this is also the most ineffective way. Of the sounds that promote falling asleep, white noise stands out, the very “shhhh” that accompanies the interference on the TV, only quiet, relaxing. For many, the sound of train wheels, the sound of sea waves or the rain beating through the window will suit.

An employee of Lenta.ru tested the Sleepace mask for 10 days. The impression remains positive: the mask allows you to relax, works in a sense like earplugs, that is, it performs the task.The sound quality is pleasant – if, of course, not compared with top-end headphones.

It fits tightly to the eyes, practically does not shine through (if you lie down so that the light source is directed directly into a small gap between the cheek and the mask, and you look down at the same time, then yes – it can shine through), but it does not press. This makes it possible to easily fall asleep if suddenly you accidentally woke up in the morning – which is especially important in summer, when it gets light early – and cannot fall asleep.

In fact, the mask is quite versatile.It can be used while traveling, you can just relax, meditate. For those who do not like to listen to something in their sleep, a mask can also come in handy as a preparation for sleep. Literally 10 minutes in the dark with relaxing music and you are already relaxed enough to sleep.

Sleep is a cycle consisting of two phases: slow and REM sleep. They are opposite and alternate in a specific order. With eight hours of sleep, we go through five cycles per night – enough to get enough sleep.Different brain structures are responsible for each stage; those who are inactive rest. Many will argue that they cannot sleep in less than nine hours, while six hours of sleep are enough for someone, to which we answer: eight hours is an average, which, however, is suitable for most people. In addition, a longer duration is often needed for those who have been sleeping for a while or have even brought themselves to chronic lack of sleep.

Beeline is holding a Gigi for Sleep campaign, in which you can receive positive reinforcement of the correct eight-hour sleep habit, which will speed up its formation.Every day, subscribers have the opportunity to get free internet for a good sleep. It is enough to press a button in the My Beeline application and the countdown will begin. You need to sleep for eight hours without leaving the application, and you will complete this small and useful quest. Details of the Gigi for Sleep campaign, as well as ASMR videos with celebrities filmed specifically for the campaign, can be found here.

When the author tested the application, it turned out that sleeping eight hours is not so easy. After a week of testing, it was possible to get the cherished megabytes only three times – two on the weekend and once on the last day.Either you go to bed later, because guests come, then you wake up earlier, because the guests did not have time to finish things, then you get up in the middle of the night and climb into the phone, because of which you need to start counting again. But at the end of the test, you pull yourself together a little and begin to approach sleep more responsibly. Yes, megabytes are good, but they are not of value, but the fact that with the help of the conditions of the promotion and the reward, an attitude towards these most necessary eight hours is developed. It is still difficult to say how much better sleep is better than an incomplete one, but the fact that at least one of the promises from the New Year’s list of promises has not failed – to improve sleep – it pleases.

One of the reasons for poor sleep (including those around) and feeling sleepy during the day is snoring. Somnologist Vladimir Kovalzon told “Lente.ru” that snoring can occur due to apnea – a short cessation of breathing – and problems in the blood supply to the brain. Apnea is often caused by stress. This is fraught with several dangers: firstly, you can bring the problem to a stroke, and secondly, there are dangers associated with lack of sleep – concentration is reduced, and this can create trouble for drivers on the road.Other possible causes: obesity, nose or palate problems.

There are several options that do not require medication or surgery. For example, you can buy a clip, a small piece that fits over your nose and widens the air passage. There are two news here: firstly, this thing is inexpensive, and secondly, completely useless and even harmful, as evidenced by a ton of reviews on the Internet. Another way – much more expensive – is to buy a “smart” bed, which costs from five thousand dollars.She will regulate how your head lies if she detects the appearance of snoring, or a person lying next to her will give her such a command. But, we repeat, it costs from five thousand dollars.

There is a much cheaper option that works in the same way. In fact, this is a “smart” pillow, it is called Nora.

You put a wireless microphone next to you, which will listen if you are snoring, and lay yourself on a pillow to which a small electric pump is connected. When the microphone hears snoring, it will command the pump to adjust the position of your head so that you do not snore.Manufacturers say that over time, snoring will generally disappear due to the fact that with the help of Nora, a person’s throat muscles are strengthened.

The most important non-material sleep device is the desire to live a full and fulfilling life. This is what makes it easy to fall asleep in anticipation of the morning and sleep the full eight hours necessary for normal wakefulness. Take part in the action “Beeline” “Gigi for a dream” and receive, in addition to health, pleasant bonuses.

It would seem that this is a rhetorical question – of course, not at all.But it is possible (at least, they write about it on the Internet). Of the many tips that can be found on the net, two of the author of the text work: follow at least an approximate sleep schedule (all the same five cycles, eight hours) and drink water in the morning, as soon as you wake up. The first teaches the body to turn on and off at a specific time, and the second awakens the body after sleep.

It is easier to wake up when it is associated with some pleasant things. If you come up with a morning ritual that includes activities that you enjoy, getting up will really be easier.That is, the first thing you will not have to get ready for work, but to drink delicious coffee, as you like, and read a little. Or something different. This will tune in correctly: you get up not only because you have to, but also because something pleasant awaits you.

In the Madrobots store, which provided Lente.ru with devices for the test, there is a fragrant SensorWake alarm clock, which we tested. The idea is simple: a device that can wake you up with a pleasant scent. SensorWake has a choice of cartridges with different scents, from chocolate and croissant to the seaside.At the programmed time, the alarm clock turns on and begins to spread the selected aroma around.

After several days of testing, the author found out that with his depth of sleep, this option is not the most suitable one. It was possible to wake up from the usual alarm clock on the phone while the room was already filled with aroma. At first it is disappointing, because waking up to the scent would be great, but later you realize that, despite everything, this is a useful device. After all, from the very morning, barely waking up, you are surrounded by a pleasant smell, familiar and desirable.Separately, you need to talk about the aroma. It has nothing to do with what the air freshener gives. It is an unobtrusive, light and pleasant smell. Perhaps this is how the smell of leather spreads in a new car. Therefore, he fulfills the goal of “creating a good morning mood” perfectly.

* Madrobots – the first gadget store in Russia with Kickstarter and Indiegogo – specializes in the distribution and production of devices that simplify the routine and make life brighter. In the catalog you can find many things from smart scales with Wi-Fi to an anti-theft backpack with a charger for gadgets.

90,000 causes and treatment at home, getting rid of RLS with folk remedies and medical methods

Restless Legs Syndrome (RLS) is usually defined by medical specialists as a specific sensory-motor disorder that is symptomatic. This pathology begins to manifest itself in the evening and at night, it is expressed in unpleasant sensations in the lower extremities, which force a person to make involuntary movements of the legs to get relief.This physical activity often leads to discomfort and sleep disturbances.

Why does this condition arise, what are its symptoms and can restless legs syndrome be eliminated? You will read about this and much more below.

Causes of restless legs syndrome

There can be a lot of reasons for the formation and development of the syndrome. They are grouped into several distinct blocks and correlated with the classification of sensorimotor disorder.

Basic classification :

• Idiopathic type .This form of the syndrome refers to the primary one, is not accompanied by additional negative symptoms (there are no neurological and somatic diseases) and has a direct hereditary nature, manifesting itself at the age of 1 to 30 years. As statistics show, restless legs syndrome of this type occurs in 50 percent of all patients with a confirmed diagnosis, and the proportion of patients with RLS in the family can reach 70 percent. A deep analysis of such cases revealed an autosomal dominant type of transmission of the syndrome, both polygenic and monogenic in nature;
• Child type .The syndrome in children under 12 years old is distinguished as a separate type of sensorimotor disorder and it depends mainly on external factors, naturally, in the absence of bad heredity. The main factors are motor hyperactivity during the day, as well as a lack of attention on the part of adults, provoking psychological disorders. RLS of this type is conventionally referred to as the primary form of the disorder, while the symptoms of the syndrome gradually increase over the years and cannot disappear on their own;
• Symptomatic type .Restless legs syndrome is secondary and most often acts as a background for various kinds of pathologies, diseases, and other syndromes.

The three main symptomatic causes of restless legs syndrome, doctors consider :

• Pregnancy . Restless legs syndrome is diagnosed in every fifth pregnant woman, most often in the 2nd and 3rd trimester. In the absence of additional pathologies, the manifestations of RLS disappear after delivery;
• Iron deficiency .Up to half of all people with anemia suffer from restless legs syndrome;
• End stage of uremia . About a third of all patients with advanced uremia have RLS.

In addition to the above reasons, can indirectly affect the increase in the risk of the syndrome, other problems, pathologies, diseases :

• Acute vitamin B12 deficiency;
• Diabetes mellitus of any type;
• Cryoglobulinemia;
• Polyneuropathies due to amyloidosis, porphyric neuropathy or prolonged alcoholism;
• Complex spinal cord injuries.
• Rheumatoid arthritis;
• Heart failure and blood vessel disease;
• The use of a number of drugs.

Symptoms of restless legs syndrome

The main clinical manifestation of RLS is increased motor activity of the legs during sleep. The prevalence of the syndrome among the population of Russia is on average about 10 percent, while every third patient has the main symptom more often than twice a week, which significantly worsens the overall quality of life.

As medical statistics show, all age groups suffer from restless legs syndrome, but most often the most striking symptoms are still found in people over 40 years old, moreover, more often in the fair sex.

The basic disorder manifests itself in a certain interval of the circadian rhythm – in the evening and at night, reaching a peak at 3-4 o’clock in the morning. Additional symptoms of the syndrome include :

• Intense pain syndrome throughout the structure of the lower extremities;
• Unpleasant sensations are complemented by itching, cramps in the legs, burning sensation, squeezing, bloating, tingling;
• Rhythmic movements of the lower extremities of a neuropathic nature, which temporarily reduce pain and discomfort.In the absence of movement at rest, pathological manifestations again increase and progress, localizing in the areas of the calf muscles and ankle;
• Formation of persistent insomnia – sleep disorders.

According to modern data, every fifth case of severe forms of insomnia in the world is directly related to the presence of restless legs syndrome in humans . The patient cannot fall asleep for a very long time, periodically wakes up in the event of an increase in discomfort. It is complaints of poor sleep that in the overwhelming majority of cases lead the patient to the doctor.

The main symptoms of restless legs syndrome are almost always supplemented by periodic limb movements – rhythmic twitching of a short-term nature and stereotyped structure. In most patients, they are limited to flexion of the big toes and fanning the rest of the toes.

More severe cases include movement in the knee and hip areas . An involuntary attack is short and rarely exceeds 5 seconds, but it forms in series at intervals of up to one minute, and the total time of manifestation can take several hours.

As a rule, neither the patient nor relatives in the case of a mild complex syndrome suspect the presence of RLS with MPC, and the patient himself goes to the doctor with complaints of sleep disorders of unexplained etiology. In the case of the primary form of the syndrome, the symptoms persist throughout the patient’s life, decreasing in proportion to the effectiveness of the therapy.

In symptomatic RLS with signs of somatic or neurological diseases, the pathology disappears completely after completion of treatment of the cause that caused the syndrome.

Diagnostics

Restless legs syndrome, although it belongs to a fairly frequent disease, is rarely correctly diagnosed due to insufficient qualifications of doctors , who are inclined to interpret complaints and external symptoms of patients as manifestations of neuroses, psychological stress, vascular diseases, joints, etc.

Correct diagnosis consists of a series of successive steps :

1. Study of patient complaints and careful analysis of the anamnesis;
2. Neurological and physical examination.
3. Comprehensive differential analysis with the exclusion of the secondary nature of RLS, its comparison with hypnic twitching, akathisia, cramps, meralgia, fibromyalgia, etc.;
4. Appointment of a biochemical blood test;
5. Study of the concentration of ferritin in blood serum;
6. Conducting electroneuromyography (for the presence or absence of polyneuropathy), as well as polysomnography with fixing the entire sleep process on the appropriate graphs;
7. If necessary, a comprehensive additional examination with other specialized specialists to confirm or exclude concomitant diseases.

How to treat restless legs syndrome

Treatment of restless legs syndrome is a complex process consisting of a number of stages. After a clear diagnosis of RLS, an appropriate individual scheme is prescribed, taking into account the current condition of the patient, the severity of the pathology, the presence of additional complications and concomitant diseases.

Drug therapy

• In a mild form of the disease – tranquilizers and sleeping pills are enough to get rid of restless legs syndrome.Typical representatives are Klonopin, Restoril;
• For idiopathic RLS and Parkinson’s disease – treatment with Miralex, which stimulates the work of dopamine;
• To neutralize convulsions in moderate and severe forms of the syndrome – Neurontin, Tegretol;
• In severe cases and severe static pain syndrome – injections of opiates. Typical representatives are Methadone, Codeine;
• In the usual course of RLS, to neutralize the pain syndrome – topical ointments.Typical representatives are Nikoflex, Relax, Nise;
• Other drugs for the treatment of concomitant diseases, complications, as well as drugs for health reasons.

Remedial gymnastics

An effective addition to drug therapy is exercise therapy, which includes:

• Stretching exercises for the calf muscles;
• Standard squat without weights;
• Long walk or 20 minutes jogging;
• Cycling or gym substitution;
• Walking on “tiptoe” with high elevation of the lower limbs;
• Flexion and extension of the lower limbs in the joints.

Physiotherapy

Includes impact on the lower extremities by manual acupressure, electrical stimulation, acupuncture, magnetotherapy, applications based on mixtures of sea mud, lymphopress, vibration massage, cryotherapy, darsonvalization of the extremities.

As a supplement, it is recommended to take multivitamin-mineral complexes, as well as homeopathic remedies.

Specialist psychotherapy sessions for patients with primary restless legs syndrome can also be a good addition.

Home treatment

At home, by prior agreement with the attending physician, it is recommended to optimize the scheme of food intake with an emphasis on a balanced diet, self-massage of the lower extremities, refusal from alcohol and tobacco smoking, adherence to the norms of proper sleep hygiene, contrasting water procedures for the legs, moderate physical and intellectual activity.

Treatment of restless legs syndrome with folk remedies

Treatment of restless legs syndrome can be supplemented by classic recipes of traditional medicine.They will be very effective in the case of the primary form of the disease and will be a component of therapy in the case of symptomatic secondary forms of the disease with manifestation of RLS.

Before using any of the recipes described below, be sure to consult with your doctor and agree on the use of funds!

• Rubbing the lower limbs with tincture . An excellent remedy for restless legs syndrome is a concentrated tincture of golden mustache available from the pharmacy.Pour some liquid into the palm of your hand and rub thoroughly all over your feet, paying particular attention to your joints. It is enough to carry out the procedure 1 time before bedtime, but daily;
• Massage with laurel oil . Take 30 grams of fresh bay leaf and fill it with 100 grams of sunflower oil. Let the agent brew for 1 day in a dark, cool place, after which you can self-massage the limbs with the addition of such “laurel oil”;
• Apple Cider Vinegar .Apple cider vinegar will help get rid of pain in RLS. 10 minutes before going to bed, rub your shins and knees with it;
• Tea . It is recommended to use herbal teas based on linden and lemon balm as a relaxing agent in the adjunctive therapy of restless legs syndrome. Packaged products of this kind are widespread in domestic pharmacies. Brew them instead of the usual tea, drinking the liquid 1 hour before going to bed;
• Horseradish compresses .Take 50 grams of chopped leaves and horseradish roots, pour 0.5 liters of vodka and let it brew for 4 days. Moisten a gauze bandage liberally with this product and apply a night compress every day;

• Home tincture . Take 100 milliliters of motherwort, peony, hawthorn, valerian tinctures, half as much eucalyptus tincture and four times less mint tincture. Stir the liquids in a container, add 10 grams of clove leaves there and leave for 1 week in a cool and dark place.Strain and consume 20-25 grams of the above homemade tincture before bed;
• Before bed, put on warm lambswool socks . Choose the longest possible products, optimally so that they reach the knee. When used regularly, they will reduce the manifestations of RLS;
• Foot bath . Take in equal proportions 50 grams of sage, valerian, oregano and nettle, pour 1 liter of boiling water. Let it brew for 5 minutes. Pour the liquid into a container and steam the feet for 15 minutes.You need to do the procedure regularly, every evening 30-40 minutes before bedtime.

Prognosis and prevention of disease

In the primary form of restless legs syndrome, caused by genetic inheritance or acquired factors, complex therapy leads to a weakening of the symptoms of manifestations and the formation of stages of remission with alternating periods of exacerbations – it will not be possible to completely get rid of RLS.

In the case of a secondary form of pathology caused by diseases and other syndromes, with the correct treatment of the underlying disease, RLS also completely disappears.

Basic preventive measures that can help reduce the risk of developing restless legs syndrome include:

• Avoiding alcohol, reducing caffeine and smoking;
• Power supply system correction;
• Creation of prerequisites for regular moderate physical activity on the lower extremities;
• Conducting home sessions of aromatherapy, relaxation, yoga, meditation;
• Warm baths before bed with sea salt;
• Long (at least 1 hour) walks a few hours before bedtime;
• Reduction of psychoemotional stress – stress and depression should be avoided, if it is impossible to control the condition, a psychologist should be consulted;
• Regular intake of vitamin and mineral complexes;
• Compliance with sleep hygiene and normalization of daily rhythms of rest and wakefulness.

When and which doctor should I contact?

Unfortunately, in most cases with the typical course of restless legs syndrome, the patient does not pay attention to the symptoms of the problem, attributing it to severe fatigue. In rare cases, a visit to a doctor begins after the formation of problems with the quality of sleep, when the manifestations of the syndrome lead to insomnia or systemic disturbances in the quality of night rest.

If you regularly have symptoms of RLS, then you should immediately contact a specialized specialist.Usually it is a neurologist – it is he who will conduct the primary diagnosis, send for additional analyzes and instrumental studies.

If the case of restless legs syndrome is atypical, secondary, there are additional symptoms of somatic or neurological disorders, then the help of other specialists may be required – from a therapist to an endocrinologist.

90,000 Iron for restless legs syndrome

Relevance

Restless legs syndrome is a common medical condition that causes uncomfortable inducements to move your legs.These stimuli occur in the evening and at night and can interfere with people sleeping well. People with restless legs syndrome often have low blood iron levels. Low blood iron levels may be part of the underlying causes of restless legs syndrome. Iron can be taken as a tablet or injected into the bloodstream. We prepared this review to find out if iron treatment results in a reduction in restless legs syndrome symptoms.

Research characteristics

We included 10 studies of iron supplements.These 10 studies included 428 people with restless legs syndrome. Not all participants had low blood iron levels. All participants were adults. Most of the studies used iron supplements by injection, while three studies used iron tablets. Iron treatment was compared with inactive treatment (ie, placebo) in nine studies. One study compared iron supplementation with another treatment for restless legs syndrome, a dopamine agonist.The main measure of interest in our review was the severity of anxiety in the legs. It is usually assessed (measured) using a 10-question questionnaire on the severity and effects of stimuli to move the legs, called the International Restless Legs Syndrome Severity Scale (IRLS). This indicator was assessed 2-4 weeks after injections of iron preparations and 12-14 weeks after taking iron preparations in the form of tablets.

Four trials received funding from drug manufacturers.Two trials received funding from the US National Institutes of Health. Two trials were funded by the institutions where the researchers worked. Two studies did not report who funded them. Four studies funded by drug manufacturers were the largest. The studies, funded by drug manufacturers, included more than half of the total number of participants.

Key results and quality of evidence

Overall, studies have shown that iron supplementation is better than placebo for reducing the severity of restless legs syndrome symptoms, although the benefit was low to moderate.These results are predominantly based on studies that used iron injections rather than iron tablets. Iron supplements were helpful even when blood iron levels were normal at the start of the study. The quality of the evidence was moderate (moderate) because not all completed studies were published, not all significant outcomes were measured, and the number of people in the studies was insufficient. Side effects were no more common with iron supplementation than with placebo.In one study, side effects were less common with iron supplementation than with other treatments commonly used for restless legs syndrome, although there is little certainty about this result. More research is needed to enable people with restless legs and doctors to make decisions about who should take iron supplements for restless legs, what types of iron to use, and for how long. The evidence is current to September 2017.

10 proven ways to get rid of insomnia without drugs

A deep sleep at night restores a person’s strength, and his absence becomes a real torment. What to do?

Chronic stress, problems at work and at home, a stormy flow of information that befalls a person literally every minute – these are the costs of the modern world that surrounds us. Sometimes the price to pay for being too active can be very high.And it is expressed in a bad appearance, or even in health problems.

One of the many and most common problems is insomnia. Some of the daytime problems continue to haunt the night. Most often, sleep is deprived of various unpleasant thoughts, excitement, anxiety. In this case, the brain does not rest, but continues to work hard, processing information. As a result, it is impossible to fall asleep in any way.

Some people mistakenly believe that sleep disturbances are completely harmless and not harmful to health.But insomnia can be just as dangerous as any other disease that harms the internal organs. It’s just not so noticeable in this case.

Irina Trubitsyna, Head of the Regional Center for Medical Prevention

A person loses a causal relationship and does not understand that the reason for suddenly arising health problems is a constant lack of sleep. When a person sleeps, his body restores the amount of energy expended per day.If sleep is interrupted or insufficient, there is a lack of energy. As a result, this leads to the gradual destruction of the body. Doctors closely associate diabetes mellitus, heart attack, hypertension, overweight with regular lack of sleep. Existing sleep problems lead to increased production of stress hormones. Stress also prevents you from sleeping normally and provokes the development of depressive states. It turns out a vicious circle. In addition, lack of sleep impairs concentration, attention and memory.

Synthetic drugs are not always able to provide the desired effect. In addition, they have many contraindications. To find the right drug, you need to go to the doctor, and then strictly adhere to all his recommendations. With prolonged use of sleeping pills, addiction develops and you have to increase the dose all the time, and this is unsafe. Therefore, it is recommended to use other methods of eliminating sleep disorders.

10 Ways to Get Rid of Insomnia Without Drugs

If you follow these simple tips, your night’s sleep should be healthy and fulfilling.And insomnia will be a thing of the past. The consequences of sleep disturbance are often frightening, but you should not immediately panic or ignore the problem, thinking that everything will go away on its own. Responsibly treat getting rid of all sorts of irritants, be patient and return bright colors to your life.

Relax thoroughly before going to bed.

You can listen to pleasant music, have a massage, drink warm milk with a spoonful of natural honey or chamomile tea.It is very good to take a bath with lavender oil before going to bed. Additionally, you can apply two to three drops of this oil directly to the pillow.

A simple exercise will help you fall asleep faster.

It is necessary to take turns tense and relax the muscles of the body – starting with the legs and ending with the head.

To relax as much as possible, not only physically, but also mentally, you need to breathe, alternating nostrils.

First, you should squeeze one of them and exhale slowly. After that, you need to take a slow breath, but with the second nostril. The first one should be clamped. It is recommended to repeat this exercise four to five times.

It is necessary to go to bed at the same time every day.

Those who are accustomed to staying up late and waking up late (“owls”) may have more severe consequences from lack of sleep than “larks.”

About a couple of hours before bedtime, turn off the overhead lights in all rooms.

Bathroom and toilet are no exception. Use night lights. Close the windows with thick curtains so that noise and light from the street do not enter the room. This is necessary in order for the body to produce enough melatonin. And this hormone, which promotes good sleep, is produced exclusively in the dark.

Monitor the temperature in the bedroom so that it does not exceed 22 ° C.