Restless Leg Syndrome
What is restless leg syndrome?
Restless legs syndrome (RLS) is also known as Willis-Ekbom Disease is a neurologic movement disorder of the limbs. It causes uncomfortable sensations in the legs and an irresistible urge to move them. Symptoms usually occur in the late afternoon or evening hours, and are often most severe at night when a person is resting, such as sitting or lying in bed. When one is inactive and sitting for extended periods (for example, in a plane or watching a movie), symptoms can occur too.
As symptoms is more severe during the night, it could become difficult to fall asleep or return to sleep after waking up. Moving the legs or walking temporarily relieves the discomfort. It can cause exhaustion and daytime sleepiness, which can strongly affect mood, concentration, job and school performance, and personal relationships. Patients are unable to concentrate, have impaired memory, or fail to accomplish daily tasks. If left untreated moderate to severe RLS can cause about a 20 percent decrease in work productivity and can contribute to depression and anxiety.
It affects about 5-15% of the U.S. population and occurs more commonly in women. It can begin at any age even in children. Many individuals who are severely affected are middle-aged or older, and the symptoms typically become more frequent and last longer with age.
More than 80 percent of people with RLS also experience periodic limb movement of sleep (PLMS) which is characterized by involuntary leg (and sometimes arm) twitching or jerking movements during sleep that typically occur every 15 to 40 seconds, sometimes throughout the night. Although individuals with RLS also develop PLMS, most people with PLMS do not develop RLS.
Restless legs syndrome (RLS) is also known as Willis-Ekbom Disease is a neurologic movement disorder of the limbs. It causes uncomfortable sensations in the legs and an irresistible urge to move them. Symptoms usually occur in the late afternoon or evening hours, and are often most severe at night when a person is resting, such as sitting or lying in bed. When one is inactive and sitting for extended periods (for example, in a plane or watching a movie), symptoms can occur too.
As symptoms is more severe during the night, it could become difficult to fall asleep or return to sleep after waking up. Moving the legs or walking temporarily relieves the discomfort. It can cause exhaustion and daytime sleepiness, which can strongly affect mood, concentration, job and school performance, and personal relationships. Patients are unable to concentrate, have impaired memory, or fail to accomplish daily tasks. If left untreated moderate to severe RLS can cause about a 20 percent decrease in work productivity and can contribute to depression and anxiety.
It affects about 5-15% of the U.S. population and occurs more commonly in women. It can begin at any age even in children. Many individuals who are severely affected are middle-aged or older, and the symptoms typically become more frequent and last longer with age.
More than 80 percent of people with RLS also experience periodic limb movement of sleep (PLMS) which is characterized by involuntary leg (and sometimes arm) twitching or jerking movements during sleep that typically occur every 15 to 40 seconds, sometimes throughout the night. Although individuals with RLS also develop PLMS, most people with PLMS do not develop RLS.
What causes Restless leg syndrome?
Primary Restless Leg Syndrome (RLS) is a idiopathic central nervous system disorder whose actual etiology is unknown. RLS has a genetic component and can be found in families where the onset of symptoms is before age 45 whereby there are specific gene variants associations.Psychiatric factors, stress, and fatigue can exacerbate symptoms of RLS.
In secondary restless leg syndrome, can develop as a result of certain conditions or factors, particularly iron deficiency and peripheral neuropathy.
Other causes/risk factors of RLS include the following:
The most widely accepted suggestion of RLS involves a genetic component, along with abnormalities in the central subcortical dopamine pathways and impaired iron homeostasis. Dopamine is needed to produce smooth, purposeful muscle activity and movement. Disruption of the dopamine pathways frequently results in involuntary movements. Thus patients with Parkinson’s disease, another disorder of the basal ganglia’s dopamine pathways, have increased chance of developing RLS.
Sleep deprivation and other sleep conditions like sleep apnea also may aggravate or trigger symptoms in some people.
Primary Restless Leg Syndrome (RLS) is a idiopathic central nervous system disorder whose actual etiology is unknown. RLS has a genetic component and can be found in families where the onset of symptoms is before age 45 whereby there are specific gene variants associations.Psychiatric factors, stress, and fatigue can exacerbate symptoms of RLS.
In secondary restless leg syndrome, can develop as a result of certain conditions or factors, particularly iron deficiency and peripheral neuropathy.
Other causes/risk factors of RLS include the following:
- Folate or magnesium deficiency
- Amyloidosis
- Diabetes mellitus
- Lumbosacral radiculopathy
- Lyme disease
- Monoclonal gammopathy of undetermined significance
- Rheumatoid arthritis
- Sjögren syndrome
- Uremia
- Vitamin B-12 deficiency
- Frequent blood donation
- pregnancy, especially in the last trimester; in most cases, symptoms usually disappear within 4 weeks after delivery
- end-stage renal disease and hemodialysis which can cause iron deficiency
- certain medications that may aggravate RLS symptoms, such as antinausea drugs (e.g. prochlorperazine or metoclopramide), antipsychotic drugs (e.g., haloperidol or phenothiazine derivatives), antidepressants TCA/SSRI (e.g., fluoxetine or sertraline), and some cold medications (e.g., diphenhydramine)
- use of alcohol, nicotine, and caffeine
The most widely accepted suggestion of RLS involves a genetic component, along with abnormalities in the central subcortical dopamine pathways and impaired iron homeostasis. Dopamine is needed to produce smooth, purposeful muscle activity and movement. Disruption of the dopamine pathways frequently results in involuntary movements. Thus patients with Parkinson’s disease, another disorder of the basal ganglia’s dopamine pathways, have increased chance of developing RLS.
Sleep deprivation and other sleep conditions like sleep apnea also may aggravate or trigger symptoms in some people.
Diagnostic criteria of Restless Sleep Syndrome
In American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), the specific criteria for RLS are:
Diagnostic criteria from the International RLS Study Group (IRLSSG) are:
Thus the diagnosis of restless legs syndrome (RLS) is based primarily on the patient’s clinical history. The doctor will take a detailed medical history including associated medical conditions and current medications followed by a neurological physical examination.
In American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), the specific criteria for RLS are:
- An urge to move the legs that is usually accompanied by or occurs in response to uncomfortable and unpleasant sensations in the legs, characterized by all of the following: (1) the urge to move the legs begins or worsens during periods of rest or inactivity; (2) the urge is partially or totally relieved by movement and (3) the urge to move legs is worse in the evening or at night than during the day or occurs only in the evening or at night
- Symptoms occur at least 3 times per week and have persisted for at least 3 months
- Symptoms cause significant distress or impairment in social, occupational, educational, academic, behavioral or other areas of functioning
- The symptoms cannot be attributed to another mental disorder or medical condition (e.g., leg edema, arthritis, leg cramps) or behavioral condition (e.g. positional discomfort, habitual foot tapping)
- The disturbance cannot be explained by the effects of a drug of abuse or medication
Diagnostic criteria from the International RLS Study Group (IRLSSG) are:
- An urge to move the legs usually but not always accompanied by or felt to be caused by uncomfortable and unpleasant sensations in the legs.
- The urge to move the legs and any accompanying unpleasant sensations begin or worsen during periods of rest or inactivity such as lying down or sitting.
- The urge to move the legs and any accompanying unpleasant sensations are partially or totally relieved by movement, such as walking or stretching, at least as long as the activity continues.
- The urge to move the legs and any accompanying unpleasant sensations during rest or inactivity only occur or are worse in the evening or night than during the day.
- The occurrence of the preceding features are not soley accounted for as symptoms primary to another medical or behavioral condition such as myalgia, venous stasis, leg edema, arthritis, leg cramps, positional discomfort, and habitual foot tapping.
Thus the diagnosis of restless legs syndrome (RLS) is based primarily on the patient’s clinical history. The doctor will take a detailed medical history including associated medical conditions and current medications followed by a neurological physical examination.
Laboratory Tests
As Restless leg syndrome could be caused by iron deficiency, a complete iron panel, including iron levels, ferritin, transferrin saturation, and total iron binding capacity, is preferable because the ferritin level can be falsely elevated in acute inflammatory states.
If other secondary causes of RLS is suspected, other blood tests are done to check for:
In some cases, sleep studies such as polysomnography (a test that records the individual’s brain waves, heartbeat, breathing, and leg movements) may identify the presence of other causes of sleep disruption (e.g sleep apnea), which may impact management of the disorder.
Diagnosing Restless leg syndrome is harder in children as they may not be able to give a proper history.
As Restless leg syndrome could be caused by iron deficiency, a complete iron panel, including iron levels, ferritin, transferrin saturation, and total iron binding capacity, is preferable because the ferritin level can be falsely elevated in acute inflammatory states.
If other secondary causes of RLS is suspected, other blood tests are done to check for:
- Blood urea nitrogen (BUN)
- Creatinine
- Fasting blood glucose
- Magnesium
- Thyroid-stimulating hormone (TSH)
- Vitamin B-12
- Folate
- Full blood count
- Pregnancy test
In some cases, sleep studies such as polysomnography (a test that records the individual’s brain waves, heartbeat, breathing, and leg movements) may identify the presence of other causes of sleep disruption (e.g sleep apnea), which may impact management of the disorder.
Diagnosing Restless leg syndrome is harder in children as they may not be able to give a proper history.
Treatment for Restless leg syndrome
Drug therapy for primary RLS is largely symptomatic; cure is possible only for secondary RLS. Moving the affected limb(s) may provide temporary relief. By treating an associated medical condition, such as peripheral neuropathy, diabetes, or iron deficiency anemia can also help relieve RLS.
Non Pharmacological therapy
1. Sleep hygiene measures : reduce/avoid intake of alcohol, nicotine and caffeine. Also to maintain a regular sleep pattern.
2. Avoiding trigger medications like SSRIs, some cold medications
3. Exercise and stretching exercise will help relieve symptoms
4. Physical modalities before bedtime: such as a hot or cold bath, using a heating or ice pack, a whirlpool bath, limb massage, or vibratory or electrical stimulation of the feet and toes.
Pharmacological therapy
1. Iron supplementation: for individuals with iron deficiency. A common side effect is upset stomach, which may improve with use of a different type of iron supplement. As iron is not well-absorbed into the body by the gut, it may cause constipation. If oral iron supplementation does not improve a person’s iron levels, they may require intravenous.
2. Anti-seizure drugs are becoming the first-line prescription drugs for those with RLS like gabapentin and pregabaklin which can be as effective as dopaminergic treatment. These drugs can decrease such sensory disturbances as creeping and crawling as well as nerve pain. possible side effects are dizziness, fatigue, and sleepiness.
3. Dopaminergic agents: increase dopamine effect, they are largely used to treat Parkinson's disease. Commonly prescribed drugs are ropinirole, pramipexole, and rotigotine to treat moderate to severe RLS. Short term side effects include nausea, dizziness. Levodopa plus carbidopa may be effective when used intermittently, but not daily. However, they can also cause impulse control disorders, such as compulsive gambling, and daytime sleepiness. However long-term use can lead to worsening of the symptoms in many individuals. With chronic use, a person may begin to experience symptoms earlier in the evening thus with time the initial evening or bedtime dose can become less effective, the symptoms at night become more intense, and symptoms could begin to affect the arms or trunk. Fortunately, this apparent progression can be reversed by removing the person from all dopamine-related medications.
4. Opioids: such as methadone, codeine, hydrocodone, or oxycodone are sometimes prescribed to treat more severe individuals who did not respond well to other medications. Side effects include constipation, dizziness, nausea, exacerbation of sleep apnea, and the risk of addiction.
5. Benzodiazepines: These are sleeping pills that can help individuals obtain a more restful sleep but they do not eliminate the leg sensations and cause daytime sleepiness, reduce energy, and affect concentration. Common drugs are clonazepam and lorazepam which are generally prescribed to treat anxiety, muscle spasms, and insomnia. As they may induce or aggravate sleep apnea in some cases, they should not be used in people with this condition. These are last-line drugs due to their side effects.
Drug therapy for primary RLS is largely symptomatic; cure is possible only for secondary RLS. Moving the affected limb(s) may provide temporary relief. By treating an associated medical condition, such as peripheral neuropathy, diabetes, or iron deficiency anemia can also help relieve RLS.
Non Pharmacological therapy
1. Sleep hygiene measures : reduce/avoid intake of alcohol, nicotine and caffeine. Also to maintain a regular sleep pattern.
2. Avoiding trigger medications like SSRIs, some cold medications
3. Exercise and stretching exercise will help relieve symptoms
4. Physical modalities before bedtime: such as a hot or cold bath, using a heating or ice pack, a whirlpool bath, limb massage, or vibratory or electrical stimulation of the feet and toes.
Pharmacological therapy
1. Iron supplementation: for individuals with iron deficiency. A common side effect is upset stomach, which may improve with use of a different type of iron supplement. As iron is not well-absorbed into the body by the gut, it may cause constipation. If oral iron supplementation does not improve a person’s iron levels, they may require intravenous.
2. Anti-seizure drugs are becoming the first-line prescription drugs for those with RLS like gabapentin and pregabaklin which can be as effective as dopaminergic treatment. These drugs can decrease such sensory disturbances as creeping and crawling as well as nerve pain. possible side effects are dizziness, fatigue, and sleepiness.
3. Dopaminergic agents: increase dopamine effect, they are largely used to treat Parkinson's disease. Commonly prescribed drugs are ropinirole, pramipexole, and rotigotine to treat moderate to severe RLS. Short term side effects include nausea, dizziness. Levodopa plus carbidopa may be effective when used intermittently, but not daily. However, they can also cause impulse control disorders, such as compulsive gambling, and daytime sleepiness. However long-term use can lead to worsening of the symptoms in many individuals. With chronic use, a person may begin to experience symptoms earlier in the evening thus with time the initial evening or bedtime dose can become less effective, the symptoms at night become more intense, and symptoms could begin to affect the arms or trunk. Fortunately, this apparent progression can be reversed by removing the person from all dopamine-related medications.
4. Opioids: such as methadone, codeine, hydrocodone, or oxycodone are sometimes prescribed to treat more severe individuals who did not respond well to other medications. Side effects include constipation, dizziness, nausea, exacerbation of sleep apnea, and the risk of addiction.
5. Benzodiazepines: These are sleeping pills that can help individuals obtain a more restful sleep but they do not eliminate the leg sensations and cause daytime sleepiness, reduce energy, and affect concentration. Common drugs are clonazepam and lorazepam which are generally prescribed to treat anxiety, muscle spasms, and insomnia. As they may induce or aggravate sleep apnea in some cases, they should not be used in people with this condition. These are last-line drugs due to their side effects.
Prognosis of Restless Leg syndrome
RLS is generally a lifelong condition for which there is no cure as of now. There are treatment options mentioned above to control the disorder, minimize symptoms and increase periods of restful sleep. Symptoms may gradually worsen with age in 2/3 of the patients. If RLS present early in adult life with mild symptoms, by age 50 years it usually progresses to severe, daily disruption of sleep leading to decreased daytime alertness resulting in reduced quality of life.
In addition, some individuals have remissions but symptoms often eventually reappear. If RLS symptoms are mild and do not affect individual’s well being and daily activities then the condition does not have to be treated. Patients with RLS and periodic leg movements of sleep (PLMS) may be at increased risk for hypertension, migraine/tension headache. Learning and memory difficulties have also been associated with RLS, presumably secondary to disrupted nocturnal sleep.
RLS is generally a lifelong condition for which there is no cure as of now. There are treatment options mentioned above to control the disorder, minimize symptoms and increase periods of restful sleep. Symptoms may gradually worsen with age in 2/3 of the patients. If RLS present early in adult life with mild symptoms, by age 50 years it usually progresses to severe, daily disruption of sleep leading to decreased daytime alertness resulting in reduced quality of life.
In addition, some individuals have remissions but symptoms often eventually reappear. If RLS symptoms are mild and do not affect individual’s well being and daily activities then the condition does not have to be treated. Patients with RLS and periodic leg movements of sleep (PLMS) may be at increased risk for hypertension, migraine/tension headache. Learning and memory difficulties have also been associated with RLS, presumably secondary to disrupted nocturnal sleep.