Welcome to today's lesson, where we'll explore Restless Legs Syndrome (RLS) and Periodic Limb Movement Disorder (PLMD), two distinct yet often interconnected neurological conditions that can disrupt sleep and impact quality of life. In this post, we will explore what these conditions are, their symptoms, potential causes, and management strategies.
Today's Content Level: All levels (Beginner, Intermediate, Advanced)
•Restless Leg Syndrome (also known as Willis-Ekbom disease) is characterized by an overwhelming urge to move the legs, particularly during periods of rest or inactivity.
Key features of RLS:
Urge to Move: The urge to move the legs is commonly associated by uncomfortable sensations described as tingling, burning, creeping, or crawling feelings in the legs.
Triggered by Rest: The discomfort usually intensifies during inactivity, especially while sitting or lying down, affecting activities like reading, watching TV, or traveling long distances.
Disrupts Sleep: Symptoms typically peak in the evening or at night, leading to difficulties in falling asleep, fragmented sleep, and resultant daytime fatigue. Movements do not occur during sleep.
Relief from Movement: Most people find temporary relief through activities like walking, stretching, or even standing up.
The mnemonic URGE can be used to remember features of RLS:
Urge to move limbs.
Rest worsens symptoms.
Getting up and moving offers temporary relief.
Evening is worse for symptoms.
•Periodic Limb Movement Disorder (PLMD) consists of involuntary movements of the limbs, predominantly the legs, during sleep.
Key features of PLMD:
Involuntary Limb Movements: Involuntary repetitive flexing and extending of the legs (kicking movements) are most common.
Disrupts Sleep: PLMD occurs only during sleep, with movements happening in bursts, often multiple times per hour, causing sleep disturbances. This often results in frequent awakenings and daytime fatigue.
Lack of Awareness: Individuals may be unaware of the movements; a bed partner may notice them.
Relationship Between RLS and PLMD 5
•RLS and PLMD often coexist, with up to 80% of RLS patients also having PLMD, but many with PLMD do not have RLS.
•The distinction between PLMD and RLS lies in the nature of the movements. PLMD involves involuntary actions and movements occur during sleep. In contrast, RLS keeps patients awake as they jerk or kick their legs to alleviate discomfort.
While the full causes of RLS and PLMD are still under investigation, several contributing factors have been observed:
Genetics/Epidemiology: Research suggests RLS and PLMD is often hereditary, with a 40-60% chance of passing RLS from parent to child, with less overall data for PLMD. Women are more likely than men to develop RLS, with a roughly equal distribution in PLMD. Prevalence increases with age.
Dopamine Dysfunction: Dopamine, a neurotransmitter, regulates motor function and sensory processing. Dysfunction in dopaminergic pathways is crucial in RLS and PLMD. RLS is linked to central dopaminergic disturbances, evidenced by reduced D2 receptor binding in the caudate and putamen (seen on SPECT/PET). The effectiveness of D2 and D3 dopamine agonists in treating RLS and PLMD also support this connection.
Iron Deficiency: Low iron levels may worsen RLS symptoms, with about 30% of individuals exhibiting lower ferritin levels (<75 ng/mL). Patients with RLS or recent exacerbations should have levels measured. Low brain iron, disturbances in iron metabolism, and brain iron transport are also involved. In CSF samples, individuals with RLS have lower iron and ferritin values and higher transferrin levels. Iron is an important cofactor in dopamine synthesis, storage, and receptor function. The endogenous opioid system may also be involved.
Pregnancy: Women often experience RLS in the last trimester, but symptoms usually resolve after childbirth. RLS is 2-3x more prevalent during pregnancy than in the general population.
Other Comorbidities: RLS or PLMD may be idiopathic, but certain conditions can increase their likelihood. Conditions include diabetes, kidney disease, uremia, peripheral neuropathy, cardiovascular disease, hypertension, migraines, Parkinson's disease, multiple sclerosis, obstructive sleep apnea, and more. Depressive disorders, anxiety disorder, and attentional disorders are also commonly comorbid.
Medications: SSRIs, mirtazapine (up to 30%), antipsychotics, dopamine-blocking antiemetics, and anti-histamines can contribute to or worsen symptoms.
Diagnosis of RLS and PMLD 8
RLS: Diagnosis is based on patient history and symptom description.
Examples of screening questions:
Do you experience uncomfortable or unpleasant sensations in your legs, such as tingling, creeping, or itching?
Do these sensations improve or go away when you move your legs (e.g., walking, stretching)?
Are the sensations worse or only present when you’re sitting or lying down?
Are the symptoms worse in the evening or at night compared to during the day?
How often do you experience these sensations, and how long do they last?
Do these symptoms interfere with your ability to fall or stay asleep?
Do you experience similar sensations in other parts of your body, like your arms?
Check Ferritin Levels: Iron deficiency does not cause RLS in all cases, but is considered one of its most significant contributors. An RLS diagnosis is supported by ferritin level <50, and even levels <75 can exacerbate symptoms.
PLMD: Diagnosis is based on patient history, including collateral information from a bed partner or roommate, and polysomnography (sleep study).
Examples of screening questions:
Has anyone told you that you move your legs or arms repeatedly during sleep?
Do you wake up during the night because of jerking or twitching movements in your legs or arms?
Has a bed partner or roommate mentioned repetitive kicking movements while you sleep?
Polysomnography: A sleep study may be performed, which records limb movements during sleep. Can differentiate the nature of movements during sleep.
General Management
Awareness and Education: Understanding these conditions and maintaining a sleep diary to identify triggers and guide treatment is crucial.
Lifestyle and Behavioral Interventions: Improving sleep hygiene, regular exercise, eating a balanced diet, and incorporating relaxation techniques such as mindfulness and deep breathing can all improve symptoms and sleep quality.
Avoid Triggers: Avoiding triggers such as caffeine, nicotine, alcohol, and certain medications (see above).
Alternative Therapies: Massage, warm baths, heating pads, ice packs, and compression devices may offer symptomatic relief.
Cognitive Behavioral Therapy: Addresses stress, anxiety, or mood symptoms, which can worsen sleep issues.
Treatment of RLS
Start with lifestyle modifications and iron supplementation if ferritin is low.
Iron Supplementation: Iron supplementation if serum ferritin <75 ng/mL.
First Line Medications:
Progress to gabapentinoids or dopamine agonists for persistent symptoms.
Gabapentinoids: Gabapentin, Pregabalin.
Second Line Medications:
Dopamine Agonists: pramipexole, rotigotine patch, ropinirole. Dopamine agonists are generally effective but require monitoring for compulsive/impulsive behaviors (e.g., gambling, shopping, hypersexuality) and rare side effects like hallucinations or agitation. More common side effects include nausea, headache, and insomnia.
Third Line and Refractory Treatments:
If symptoms are severe and refractory to first line options, you may consider the following third line treatments.
Low-Potency Opioids: Codeine, tramadol, methadone (for severe, treatment-resistant cases).
Benzodiazepines: Clonazepam or other benzodiazepines.
Other Medications: Clonidine, baclofen, carbamazepine, B12, folate.
Long-term use of benzodiazepines or opioids should be approached cautiously.
Treatment of PLMD
Start with lifestyle modifications.
Focus on RLS Symptoms: When PLMS is linked to RLS, prioritize RLS management.
For PLMS associated with other sleep disorders, independent treatment of PLMS is rarely required.
There is limited data regarding management of PLMD. In scenarios where PLMD severely disrupts sleep, dopamine agonists, muscle relaxants, or anticonvulsants may be trialed.
Medication Options:
Dopamine Agonists: pramipexole, rotigotine patch, ropinirole.
Gabapentinoids: gabapentin, pregabalin.
Clonazepam and other benzodiazepines may reduce arousals rather than eliminate PLMS.
Limited data support valproate and selegiline in small, uncontrolled studies.
Conclusion
•Nice work. I hope today's less helped you gain a better understanding of RLS and PMLD. In the upcoming lesson, we will cover Obstructive Sleep Apnea (OSA) and other medical causes of sleep disorders.
Resources for today's post include:
Articles from UpToDate and PubMed referenced above.
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