Presentaties ISMC - RLS
217 important questions on Presentaties ISMC - RLS
What is the oral treatment for RLS with low serum ferritin levels?
- Ferrous sulfate 325 mg combined with vitamin C 100 mg twice a day
- Effective for RLS in patients with serum ferritin level ≤ 75 mg/L
- Based on one Class II study, Level C
What hormonal changes occur in pregnancy related to RLS?
- Prolactin, estrogen, and progesterone levels rise, especially in the third trimester.
- Prolactin correlates with PLMs; secretion increases after delivery.
- Estradiol suppresses dopamine production/release.
- Progesterone enhances neuronal excitability, peaking in the third trimester, possibly causing hyperreflexia and leading to PLMs and RLS.
Describe the intravenous treatment for moderate to severe RLS.
- Ferric carboxymaltose 1000 mg is effective for moderate to severe RLS
- Serum ferritin level < 300 mg/L with transferrin saturation < 45%
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How does transient RLS during pregnancy impact future RLS risk?
- Transient RLS in pregnancy increases chronic RLS risk fourfold compared to those who never had RLS during pregnancy.
- RLS in one pregnancy boosts future pregnancy RLS risk by nineteen times.
What is the prevalence and trend of RLS in pregnancy?
- 21% prevalence in pregnancy, higher than general population.
- Higher trend as trimesters progress:
- Trimester I: 8%
- Trimester II: 16%
- Trimester III: 22%
What does the graph on secondary RLS during pregnancy indicate?
- Secondary RLS: Associated with pregnancy.
- IRLS Scale: Peaks around 30 weeks.
- Hemoglobin (Hb): 7.9 g/dl at peak.
- Ferritin Level: 85 mcg/l.
- Trend: Decrease after 40 weeks.
How do RLS symptoms change post-partum, and what role does iron deficiency play?
- Mostly rapid remission post-partum.
- Prevalence drops to 4%.
- Persistent cases existed before pregnancy.
- No lower ferritin levels in pregnant women with RLS versus without.
What does the graph indicate about RLS during pregnancy and related blood metrics?
- Secondary RLS: Associated with pregnancy.
- IRLS Scale Increase: Peaks around 30 weeks at above 30.
- Decline by 50 Weeks: Falls below 20.
- Hb Level: 7.5 mmol/l.
- Ferritin Level: 45 mcg/l.
What are the key features of Secondary RLS associated with pregnancy according to the graph?
- Secondary RLS: Associated with pregnancy.
- Weeks: Symptoms appear from 20 weeks.
- IRLS Scale: Starts at 20, increases to ~30.
- Iron Supplementation: Administered around 30 weeks.
- Delivery Details:
- Blood loss: 850 cc.
- Hemoglobin: 5.9 mmol/L.
- Ferritin: 150 mcg/L.
What does the graph illustrate about RLS and pregnancy?
- Title: RLS associated with pregnancy
- IRLS Scale: 20
- Weeks pregnant: ~20
- Treatment started: Ferrofumerate 3 times a day, 200 mg
What does the graph show about the serum ferritin levels in an RLS patient during pregnancy?
- A young woman with moderate-to-severe RLS experienced fluctuations in serum ferritin levels.
- After intravenous iron (IV iron) treatment, levels increased significantly.
- RLS symptoms remitted.
- During pregnancy, RLS relapsed, coinciding with lower ferritin levels.
What are the teratogenic effects of Levodopa/carbidopa in pregnancy?
- Class: C
- Effects: Limited human data; causes visceral and skeletal malformations in animal studies (rabbits).
- Keywords: Levodopa, carbidopa, visceral malformations, skeletal malformations.
How does Pramipexole affect pregnancy?
- Class: C
- Effects: Inhibits prolactin synthesis, diminishing lactation.
- Keywords: Pramipexole, dopamine, prolactin, lactation.
What are the steps for accurately diagnosing RLS/WED?
- Confirm 4 of 4 core RLS/WED features.
- Rule out mimics, like cramps and edema.
- Assess severity: frequency and impact.
- Check for comorbid depression.
What kind of therapy would you consider for a 28-year-old female?
- Cognitive Behavioral Therapy (CBT): Effective for anxiety and depression.
- Dialectical Behavior Therapy (DBT): Helps manage emotions.
- Psychodynamic Therapy: Explores past influences.
- Group Therapy: Provides peer support.
What nonpharmacologic strategies are recommended for RLS/WED during pregnancy?
- Educate on natural course during pregnancy.
- Assess iron status.
- Moderate-intensity/low-impact exercise.
- Avoid exacerbating factors.
- Consider other interventions.
What are the pregnancy risks associated with Clonazepam?
- Class: D
- Effects: Risk of birth defects, fetal dependency, floppy baby syndrome; neonatal withdrawal when used late in pregnancy.
- Keywords: Clonazepam, benzodiazepines, birth defects, fetal dependency, floppy baby syndrome.
What are the main complaints of the 28-year-old pregnant woman related to her sleep and leg sensations?
- Progressive bad sleep over 4-6 weeks.
- Paresthesia in calves and upper legs, both sides.
- Irresistible urge to move legs in bed, evening.
- Movement eases the urge.
- Tiredness without excessive sleepiness.
- Concern for fetus development due to sleep deprivation.
How should iron levels be assessed and addressed in RLS/WED treatment?
- Check hemoglobin, ferritin, iron, TIBC, % saturation.
- Ferritin >75 mcg/L: continue oral iron.
- Ferritin
Describe the effects of Oxycodone during pregnancy.
- Class: B (D if chronic)
- Effects: Neonatal withdrawal syndrome; sedation in newborns when excreted in breast milk.
- Keywords: Oxycodone, neonatal withdrawal, sedation, breast milk.
What symptoms and history are noted for the 28-year-old female?
- Symptoms:
- Uncomfortable feeling in legs
- Urge to move
- Sleeping problems (4-6 weeks)
- History:
- Pregnant 21 weeks
- No medication or intoxication mentioned.
What treatments are suggested for refractory RLS/WED during pregnancy?
- Carbidopa/levodopa ER 25/100 to 50/200 mg in the evening/night.
- Low-dose clonazepam 0.25 to 1 mg in the evening.
- Severe cases: consider low-dose oxycodone.
- Reassess periodically, reassess at delivery.
What are the effects of Methadone on pregnancy?
- Class: B/C; D if high dose
- Effects: No congenital defects; risks of low birth weight, neonatal withdrawal, sudden infant death.
- Keywords: Methadone, birth weight, withdrawal, infant death.
What is the guidance for RLS/WED treatment during lactation?
- Reassess iron status.
- Gabapentin 300 to 900 mg in the evening/night.
- Low-dose clonazepam 0.25 to 1 mg in the evening.
- Very severe cases: consider low-dose tramadol.
What concerns exist for Clonidine use in pregnancy?
- Class: C
- Effects: Inadequate human studies; excreted in human milk.
- Keywords: Clonidine, human studies, milk.
What were the results after three months for the 7-year-old patient?
- Ferritin levels reached 60 mcg/l.
- Symptoms showed improvement: more restful in the evening and better sleep initiation.
- Iron supplementation was stopped to evaluate the patient further.
Why should dopamine-related treatments be avoided during lactation for RLS/WED?
- Dopamine inhibits prolactin production.
- Levodopa and dopamine agonists should not be used due to lactation interference.
How are Folate and Iron used during pregnancy?
- Class: A
- Effects: Essential nutrients; used in prenatal multivitamins.
- Keywords: Folate, Iron, nutrients, multivitamins.
What is the role of Magnesium in pregnancy?
- Class: B
- Effects: Used in treating eclampsia; may benefit RLS.
- Keywords: Magnesium, eclampsia, RLS.
What treatments and outcomes were observed in the 7-year-old with low ferritin levels?
- Ferritin was 25 mcg/L, sat 16%.
- Iron levels (iron, Hb, MCV, MCH, MCHC) were normal.
- Serum ferritin > 50 ug/ml showed improvement with iron therapy.
- Administered 3 mg/kg/day elemental ferrous iron sulfate for 3 months.
- Dosage tapered over 1 year.
- Improvements in iron levels and limb movements for up to 2 years.
- IV iron supplementation showed promising results.
What are the current considerations for pediatric RLS treatment?
- No FDA/EMA approved drugs for pediatric RLS.
- Gabapentin and clonazepam used off-label.
- Dopaminergic agonists limited to pediatric sleep specialists.
- Assess iron levels; treat with oral ferrous sulfate if needed.
What is the association between iron levels and ADHD?
- Oral iron supplementation partially improved ADHD symptoms (Server et al., 1997).
- Lower ferritin levels were observed in ADHD patients compared to controls (Konofal et al., 2004).
- Serum [Ferritine] was inversely correlated with ADHD severity (Konofal et al., 2004).
Describe the symptoms and diagnosis consideration process for RLS in children.
- Symptoms include an urge to move legs, worse in evenings/rest.
- Diagnosis considers family history, restlessness, sleep disturbances.
- Evaluate daytime symptoms, comorbidities, recommend nonpharmacological interventions.
How is iron deficiency addressed in children with RLS?
- Measure fasting iron and ferritin levels.
- If levels are
What is the effect of MPH on RLS and PLMS in patients with ADHD?
- RLS (+ ADHD) effects with MPH have never been measured.
- MPH reduces PLMI in ADHD patients.
- Research by Sobanski et al., 2008.
How does dopamine affect RLS and ADHD?
- RLS and PLMS improve with dopamine.
- Dopamine does not improve ADHD symptoms.
What are the connections between RLS and ADHD in children?
- RLS in children can lead to sleep deprivation.
- Sleep deprivation may cause ADHD-like symptoms.
- RLS and ADHD share symptoms, risking misdiagnosis.
- They have shared pathophysiology:
- Dopaminergic pathophysiology
- Iron deficiency
What is the relationship between PLMS and ADHD in children?
- PLMS occurs in 44% of children with ADHD (up to -90%).
- ADHD is linked to 26%-64% prevalence of PLMS.
- 15% of ADHD children have PLMS, compared to 0% in controls.
What are the percentages of RLS and ADHD in children and adults?
- Children:
- RLS: 2 - 3.6%
- ADHD: 3 - 6%
- Adults:
- RLS: 5 - 10%
- ADHD: 1 - 2%
How prevalent is RLS among children according to the data?
- RLS is present in 63%-74% of children.
- Studies emphasize a link between PLMS, ADHD, and RLS.
What are the diagnostic criteria for Restless Legs Syndrome (RLS) in children?
- Urge to move due to uncomfortable sensations in the legs.
- Symptoms worsen during rest.
- Symptoms are relieved by movement.
- Worse in the evening or night.
- Not due to other conditions (e.g., myalgia, arthritis).
- Children should describe symptoms in their own words.
What are the percentages of RLS in ADHD and ADHD in RLS for children and adults?
- Children:
- RLS in ADHD: 6.8 - 44%
- ADHD in RLS: 10.3 - 25%
- Adults:
- RLS in ADHD: 20 - 34.5%
- ADHD in RLS: 8.5 - 27.6%
What are the symptoms and treatment details for the 7-year-old's ADHD?
- Age: 7 years
- Medication: MPH 2 dd 10 mg
- Symptoms:
- Excessively fidgets or squirms
- Difficulty remaining seated
- Easily distracted
- Difficulty focusing
- Difficulty waiting turn
- Interrupts/blurts out answers
- Difficulty following instructions
- Difficulty sustaining attention
- Moves from one activity to another, often not completing
- Often talks excessively
- Often loses things
- Engages in seemingly dangerous activities
- Improvement: Better during the day, not in the evening
What are the essential criteria for diagnosing Restless Legs Syndrome (RLS)?
- Urge to move/dysaesthesia:
- Begins/increases at rest
- Relieved by movement
- Worse in evening/night
- Not solely due to another condition
- Causes concern, distress, sleep disturbance
What symptoms and behaviors suggest Restless Legs Syndrome in a 7-year-old?
- Pain in legs during bedtime, requiring leg rubbing.
- Difficulty initiating sleep.
- Crying and rubbing lower legs at 19:00.
- Must move around to relieve pain.
- Occurs 3-4 times a week, lasts 1 hour.
- Mother was recently diagnosed with RLS.
- Describes pain as burning when wanting to sleep.
What associated criteria are considered when diagnosing RLS?
- PLMS & PLMW are uncertain
- Effect of dopaminergic medication is uncertain
- Positive family history (1st grade) is present
- Lack of sleepiness during the day is present
What are the main issues and history of the 7-year-old male patient?
- Sleep Problems:
- Difficulty initiating and maintaining sleep
- Tossing and turning
- Painful legs
- History:
- Diagnosed with ADHD
- Medication:
- Methylphenidate 2 times daily, 10 mg
What is the main topic presented in the text?
- The main topic is children.
- The information provided is minimal, focusing solely on the word children.
What changes and outcomes were implemented for Bart regarding dopamine wreck at age 56?
- Gabapentin: Switched, side effects, little RLS effect.
- PSG and POSA performed.
- Ferritin: 36ug/L, oral substitution with low vitamin C.
- CBT: Implemented.
- Longacting DA: Not well tolerated.
- Sifrol: 0.25mg twice daily.
- Impulses manageable, side effects gone.
- Mood and anxiety improved.
- Insomnia and IRLS scale improved.
What are the common side effects of dopamine agonists?
- Nausea/vomiting
- Fluid retention
- Insomnia
- Hypersomnia
- Nasal congestion
- Hallucinations
- Morning rebound of symptoms
- Augmentation
What are some key points about Impulse Control Disorders related to dopamine agonists?
- Reported with dopamine agonists; approximately 17%
- Examples: pathologic gambling, impulsive shopping, sorting, hoarding, hypersexuality
- Occur ~9 months after starting medication
- Discussed at each follow-up visit
What are the serious side effects of dopamine agonists?
- Sleep Attacks
- Orthostatic Hypotension
- Compulsive Behaviors
- Augmentation
- Dyskinesia
- Hallucinations
What medications has Bart switched between for his condition?
- Several switches: Sifrol, Glepark, Oprymea, Pramipexol.
- Currently uses: glepark 0.25mg.
- Doses: One and a half tablet twice daily at 17:00 and 23:00.
What treatment was initially given to Bart for OSA and what medication was started?
- Treated OSA with PAP.
- Started on Sifrol 0.125mg twice daily.
When do Bart's restless leg symptoms typically begin?
- Restless leg symptoms start at 15:00.
- Occasionally feels sensations in his arms related to the symptoms.
What are the essential criteria for diagnosing Restless Legs Syndrome (RLS)?
- Urge to move/dysaesthesias:
- Begins or increases at rest (+)
- Relieved by movement (+)
- Worse in the evening/night (+)
- Not solely due to another condition (+/-)
- Symptoms cause concern/distress, sleep disturbance, or daytime impairment (++++)
What side effects did Bart experience after several years of medication?
- Increased libido for 8 months.
- Involuntary movements leading to earlier medication intake.
- Sleepiness post-medication and during day.
- Auditive and sensory hallucinations.
- Fluid retention in legs.
- Headaches.
- Hypotension.
What changes has Bart experienced relating to snoring and PAP usage?
- He no longer snores after losing some weight.
- Stopped using PAP 2-3 years ago.
- Reasons: Leakage and comfort problems.
What factors contribute to Bart's insomnia?
- Insomnia partly due to Restless Leg Syndrome (RLS).
- Mainly due to feelings of guilt and anxiety.
What symptoms and issues does Bart, age 56, experience with his leg sensation condition?
- Referral by GP.
- Soda pop sensation in legs, either or both.
- Walking or getting out of bed relieves symptoms.
- Present during sleep onset for 15 years.
- Starts before dinner for 2 years, 5/7 nights.
- Results in severe social implications and variable insomnia.
What are the associated criteria for Restless Legs Syndrome (RLS)?
- PLMS & PLMW (+)
- Effect of dopaminergic medication (+)
- Positive family history (1st grade) (+)
- Lack of sleepiness during the day (+)
What does "Dopamine Wreck" in the context of RLS indicate?
- Restless Leg Syndrome is linked to dopamine issues.
- Symptoms can include:
- Uncontrollable repetitive behaviors
- Hypersensitivity to reward
- Impaired quality of life
- Activities: Sex, Shopping, Binge eating, Gambling
What steps should be taken in mild augmentation for restless legs syndrome?
- Split dose
- Advance dose or switch to α2δ ligand
- Increase dose within limits, or switch to long-acting dopamine agonist
How is Restless Leg Syndrome (RLS) related to pregnancy?
- RLS can be common in pregnancy.
- Hormonal changes might contribute.
- Effects can include:
- Sleep disturbances
- Discomfort in legs
- Need for lifestyle adaptations
What is augmentation in the context of RLS symptoms due to medication?
- Increase in one or more RLS symptoms due to medication.
- Frequency: Symptoms occurring more often.
- Duration: Symptoms lasting longer.
- Number of body parts affected: More areas impacted.
- Intensity: Symptoms become stronger.
How is severe augmentation managed according to the flow chart?
- Eliminate short-acting dopamine agonist
- Choose long-acting dopamine agonist or α2δ ligand
- Cross-titration, switch, or drug holiday
How is Restless Leg Syndrome observed in children?
- Children can also develop RLS.
- Symptoms may include:
- Discomfort in legs
- Urge to move, especially at night
- Impacts on sleep and behavior
What issues did Peter, 74, experience during travel?
- Winter Holiday to Austria: Restless Leg Syndrome (RLS) returned.
- Roadtrip to Spain: RLS came back again.
What preliminary checks and modifications are advised before addressing augmentation?
- Check serum ferritin levels
- Eliminate exacerbating factors, including low ferritin (
What does Peter's polysomnography (PSG) data indicate at age 74 while on Methadone?
- General Hypopnea: Detected
- Obstructive Apnea: Present
- Mixed Apnea: Observed
- Central Apnea: Present
- SpO2 Desaturation: Significant
- PLM (Periodic Limb Movement): Occurences present
- Snore Events: Identified
What were the results of Peter's treatment for severe RLS with augmentation?
- On 5mg Methadone, no side effects.
- RLS improved (IRLS scale 32 to 4).
- Insomnia improved (ISI 16 to 1).
- Rotigotine tapered slowly.
- EDS reduced from 14 to 6.
- Mixed sleep apnea improvement.
What were the results of Peter's lab tests and their implications?
- Ferritin levels are >100ug/L, indicating high saturation.
- Iron infusion is unsafe due to risk of overload.
- Ferritin is lower than in 2020.
What are the components shown in the PSG on Oxy graph?
- Hypnogram: Tracks sleep stages
- Position Summary: Displays sleeping positions
- SpO2: Measures oxygen saturation
- General Hypopnea, Obstructive Apnea, Central Apnea, Mixed Apnea: Indicate breathing issues
- RERA, Arousal, SpO2 Desat: Track sleep disruption
- PLM: Monitors leg movements
- Snore EM: Detects snoring
How did Gabapentin tapering affect Peter's condition?
- Initial 2-3 weeks difficult.
- Restless Leg Syndrome (RLS) improved slightly post-taper.
- Insomnia worsened during tapering.
What are the hemoglobine and MCV values, and their reference ranges?
- Hemoglobine: 10.1 mmol/l
- Reference range: 7.3 - 10.7 mmol/l
- MCV: 93 fl
- Reference range: 81 - 96 fl
What is the impact of Zolpidem on Peter's sleep and its side effects?
- Taken every 3rd night.
- Provides 6 hours of sleep.
- Nights without Zolpidem worsen insomnia.
- Causes nausea and dizziness.
What steps were taken for Peter, 74 years old, to address his condition?
- Explain and educate patient.
- Check ferritin levels.
- Taper gabapentin dosage.
- Behavioral Sleep Therapy (CBTi with RLS knowledge).
- Add Zolpidem medication.
- MRA brace used intermittently; limited effect.
- PAP not tolerated.
- Conducted Polysomnography.
List the glucose levels and reference ranges for fasting and non-fasting states.
- Glucose: 6.3 mmol/l
- Non-fasting: 3.3 - 7.8 mmol/l
- Fasting (Nuchter): 4.0 - 6.0 mmol/l
How does Zolpidem affect Peter's PLM condition according to his wife?
- Enables him to sleep through PLMs.
- Previously hindered sleep; would wake and get out of bed.
What medication adjustments were made for Peter?
- Transition from Oxycodone to Methadone.
- Taper Rotigotine patch.
What treatments were used for Peter, 74 years old, and what were their effects?
- Ferrous fumarate: Used regularly.
- Cannabis tea: Caused unpleasant feeling.
- Pregabalin: No effect.
- Inhibin: No effect.
- Drug Holidays: Caused depression symptoms, last in Dec 2020.
- Simvastatin: Stopped for 6 months; no effect on RLS or insomnia.
- Levodopa/carbidopa: Occasional use.
- Clonazepam: Used.
What are the sodium and potassium levels with their reference ranges?
- Sodium (Natrium): 141 mmol/l
- Reference range: 135 - 145 mmol/l
- Potassium (Kalium): 4.1 mmol/l
- Reference range: 3.5 - 5.0 mmol/l
What were the findings from Peter's previous medical workup?
- No neurological abnormalities.
- MR-lumbar spine: age-appropriate degeneration.
- Polysomnography 2016: OSA, mandibular appliance.
- Polysomnography 2020:
- Sleep misperception: 6h 35m vs 3h 15m.
- PLMI: 9.1/h (2.9 arousal index).
- AHI: 4.8/h with MRA.
- Ferritin (06-09-2020): 227 µg/L; iron parameters normal.
Provide the creatinine, GFR CKD-EPI values, and their reference ranges.
- Creatinine (Kreatinine): 83 umol/l
- Reference range: 62 - 106 umol/l
- GFR CKD-EPI: 81 ml/min/1.73m²
- Reference range: >60 ml/min/1.73m²
What treatments and lifestyle factors are noted for Peter, a 74-year-old with RLS?
- Drug holidays: Several lasting 3 months, benefit up to 1.5 years.
- Rotigotine: Higher dose might help but causes faster augmentation.
- Oxynorm: Relieves RLS symptoms but doesn't improve sleep.
- Gabapentin: Uncertain effect on symptoms.
- Sleep issues: Daytime sleepiness, nighttime insomnia with/without RLS.
- Lifestyle:
- Alcohol: 0 units/week.
- Smoking: Never smoked.
- Caffeine/theine: None.
- Drugs: None.
What are the urea and iron values along with their reference ranges?
- Urea (Ureum): 5.6 mmol/l
- Reference range: 2.9 - 7.5 mmol/l
- Iron (IJzer): 28.6 umol/l
- Reference range: 10.0 - 30.0 umol/l
Who is involved and what are the key questions posed for reflection?
- Peter, 74 years old is involved.
- Three questions:
- What do you think this is?
- What else would you like to know?
- What would you do?
State the ferritin, transferrin levels, and reference ranges.
- Ferritin: 128 ug/l
- Reference range: 25 - 250 ug/l
- Transferrin: 2.3 g/l
- Reference range: 2.0 - 4.1 g/l
What is the transferrin saturation percentage and its reference range?
- Transferrin Saturation (Transferrine-verz.): 48%
- Reference range: 20 - 50%
When and how was Peter diagnosed with RLS, and what treatment did he initially receive?
- Debut at age 13; diagnosed at 25 with Restless Leg Syndrome (RLS) by GP.
- Initially, no therapy was available.
- Treatment began 15 years ago with Pramipexole (Sifrol).
What are the key considerations for using oral iron in the treatment of RLS?
- Iron deficiency RLS:
- Ferritin < 50-75 ng/ml
- % Iron saturation < 16%
- TIBC > 400%
- Iron < 60 ng/ml
- 325mg Ferrous Sulfate (65mg elemental iron)
- Combine with low-dose Vitamin C
- Maintain 2-hour interval with dopaminergic medication
How did Peter's RLS symptoms progress, and what changes were made to his treatment?
- Strong fluctuations in symptoms; worse after age 50.
- Switched to Rotigotine patches in 2014 as Pramipexole was ineffective.
- Symptoms intensified, requiring higher doses.
What are the key components of dopaminergic therapy for RLS?
- Dopamine agonists: Pramipexol, Ropinirol, Rotigotine.
- Dosing: Schedule 2 hours before symptom onset.
- Strategy: Lower and slower total dose.
- Levodopa: Occasionally used due to high augmentation rate.
What are the guidelines for administering intravenous iron for RLS?
- Use for patients with low/normal ferritin levels intolerant of oral iron
- Rapid response needed (effect in 6 weeks)
- No immediate effects expected
- Iron dextran has an anaphylaxis risk
- Monitor iron overload: % Iron saturation > 45%
- Recheck serum ferritin every 3-4 months, then less frequently
Describe Peter's current symptoms and how they affect his daily life.
- Symptoms start early afternoon, become painful in the evening.
- Involuntary movements disturb sleep, affecting him and his wife.
- Afraid to change medication or go to bed.
What lifestyle changes are recommended for severe IRLS scores?
- Regular sleep/wake cycles
- Regular exercise
- Stop smoking
- For severe cases: Importance of lifestyle adjustments and discussing RLS medication options.
When should α₂δ calcium channel ligands be considered for RLS treatment?
- First-line when pain, anxiety, insomnia, or augmentation are factors.
- More effective in symptom onset after 40+ years.
- Includes Gabapentin, Gabapentin enacarbil, Pregabalin.
What medications is Peter currently using for his RLS and other conditions?
- Simvastatin 20mg once daily
- Montelukast 10mg once daily
- Gabapentin 600mg twice daily
- Oxycodone 5mg as needed
- Oxycodone SR 10mg twice daily
- Rotigotine patch 2mg/24hr
What are the treatment categories for a 48-year-old with varying severity on the IRLS scale?
- Mild (0-10):
- Lifestyle: Adjustments advised
- Underlying disease: Evaluate and treat
- Medication: Review current meds
- RLS medication: Unlikely needed
- Moderate (11-20):
- Lifestyle: Encourage improvements
- Underlying disease: Address conditions
- Medication: Potential changes
- RLS medication: Consider if symptoms persist
- Severe (21-30):
- Lifestyle: Significant changes recommended
- Underlying disease: Critical treatment
- Medication: Assess necessity for change
- RLS medication: Likely needed
- Very severe (31-40):
- Lifestyle: Intense modification
- Underlying disease: Urgent management
- Medication: Discontinue harmful drugs
- RLS medication: Essential intervention
Discuss the use of opioids in RLS treatment.
- Short-acting: Codeine, oxycodone, hydrocodone (T₁/₂ 4 hrs), Propoxyphene (T₁/₂ 6 hrs).
- Long-acting: Oxycontin (T₁/₂ 8-10 hrs), Methadone (T₁/₂ 16-22 hrs), Fentanyl patch (T₁/₂ 72 hrs).
What is the severity of RLS for a 48-year-old female and how is it measured?
- Frequency: Daily
- John Hopkins RLS Severity Scale (JHS):
- 0: No RLS
- 1: Bedtime/night complaints = Mild RLS
- 2: 18.00 hrs complaints = Moderate RLS
- 3: Afternoon/whole day complaints = Severe RLS
- International RLS Scale:
- 10-item scale: 28/40 = Severe RLS
What should be considered when using (non) benzodiazepines for RLS?
- No preference: Clonazepam vs. others.
- Short T₁/₂ advised to minimize side effects.
- Particularly important for elderly.
- Options: Temazepam, Zolpidem, Zopiclone.
What are the key details about a 48-year-old female with RLS?
- Condition: Restless Legs Syndrome (RLS)
- Type: Idiopathic
- Family history: Present
- Triggering features:
- Medical history: S1 Radiculopathy
- Physical examination: Normal
- Blood examination: Hb, ferritin (85 mcg/l), CRP normal
- Medication: None
What are the differences between S1 radiculopathy and RLS in a 48-year-old woman?
- S1 radiculopathy:
- One side (right)
- Same anatomic location
- Other sensation
- RLS (Restless Leg Syndrome):
- Two-sided (simultaneous/alternating)
- Diverse locations (calves, upper legs, arms)
- Physical examination shows no signs of radiculopathy.
What are the essential criteria for diagnosing Restless Legs Syndrome (RLS)?
- Urge to move/dysaesthesia
- Begins or increases at rest
- Relieved by movement
- Worse in the evening/night
- Not solely due to another condition
- Causes concern, distress, or daytime impairment
What is the difference in prevalence of PLMS between those with RLS and healthy individuals?
- PLMS is more common in individuals with RLS than in healthy individuals.
- PLMS is significantly larger in the RLS group.
- In healthy people, only minor representation indicates the presence of LMS.
What are the associated criteria linked with Restless Legs Syndrome (RLS)?
- PLMS & PLMW present
- Effect from dopaminergic medication (unclear)
- Positive 1st-grade family history
- Lack of sleepiness during the day
What information is provided in the limb movement analysis?
- Limb Movements (LM):
- Total Number: 113
- Rate: 31.8/hour
- Periodic Limb Movements (PLM):
- Total Number: 97
- Rate: 27.3/hour
- With Arousal: 21.4/hour
- Mean Duration:
- Full: 2.5-2.6s
- Interval:
- PLM Mean Interval: 30.2 seconds
- Index:
- Periodicity Index: 0.877
How does the prevalence of PLMS change with age?
- 20 – 40 years: Prevalence of PLMS is around 10%.
- 40 – 60 years: Increases to approximately 30%.
- Over 60 years: Prevalence exceeds 40%.
What are the essential criteria for diagnosing Restless Leg Syndrome (RLS)?
- Urge to move/dysaesthesias:
- Begins or increases at rest
- Relieved by movement
- Worse in the evening/night
- Not accounted for by other conditions
- Symptoms cause concern, distress, or impairment
What health factors might be associated with a 48-year-old woman smoking 20 cigarettes per day?
- Possible Restless Legs Syndrome association.
- Intoxication: 20 cigarettes/day.
- Family history: Mother and daughter with similar complaints.
What are the associated criteria for Restless Leg Syndrome (RLS)?
- PLMS & PLMW: Uncertain
- Effect of dopaminergic medication: Uncertain
- Positive family history (1st grade): Present
- Lack of sleepiness during the day: Present
What are the key symptoms and characteristics described for the 48-year-old patient?
- Symptoms since age 37
- Itching in calves, urge to move
- Symptoms worsen at rest
- Start late afternoon (17:00 PM)
- Movement alleviates symptoms
- Frequency increased to 5-6x/week
- Intensity VAS 8/10
- Sleep initiation/maintenance issues
- Daytime tiredness, no EDS
What are the key issues experienced by the 48-year-old female patient?
- Problems initiating and maintaining sleep
- Daytime tiredness
- Potential restless legs
- History includes Radiculopathy S1 R (1998) and tonsillectomy
- No current medication
What are some nonpharmacological treatment options for RLS to try?
- Cold/hot baths or showers
- Massage
- Relaxation/Yoga
- Mental engagement
- Light to moderate exercise
- Appropriate sleep-wake schedule
- CBT
- Counter pressure
What are Eva's key health details and recommendations?
- Age: 36 years
- Ferritin levels: 118 μg/L
- Caffeine intake: 14 units/day
- Recommendation: Stop drinking coffee and black tea
- Outcome: RLS acceptable, occasional sensations (~once a month)
What should be avoided in nonpharmacological treatment for RLS?
- Nicotine, caffeine, alcohol
- Antidepressants
- Central-acting antihistamines
- Dopaminergic antiemetics
- Antipsychotics
- Sleep deprivation
- Excessive exercise
What is included in the essential criteria for Restless Legs Syndrome (RLS)?
Key factors for RLS include:
- Urge to move/dysaesthesias:
- Begins/increases at rest
- Relieved by movement
- Worse in evening/night
- Not solely another condition
- Causes concern/distress/sleep disturbance
What are the essential criteria for diagnosing RLS according to the chart?
- Urge to move or dysaesthesia:
- Begins or increases at rest
- Relieved by movement
- Worse in the evening/night
- Not solely from another condition
- Causes distress or daytime impairment
Describe the associated criteria for Restless Legs Syndrome (RLS).
Factors connected to RLS are:
- PLMS & PLMW: Not specified
- Effect of dopaminergic medication: Not specified
- Positive family history (1st grade): Present
- Lack of sleepiness during the day: Mixed presence
What are Eva's symptoms and previous treatments?
- Insomnia since pregnancy of her 2-year-old boy
- Keeps busy at night
- Strange feelings in calves/feet
- Tiredness and lack of energy during the day
- Previous treatment:
- Inhibin: no effect
- Pramipexole 0.125mg: side effects
What are the associated criteria for RLS in the chart?
- PLMS & PLMW
- Effect of dopaminergic medication
- Positive family history (1st grade)
- Lack of sleepiness during the day
What are some common descriptions of Restless Legs Syndrome (RLS) symptoms?
Common Restless Legs Syndrome symptoms include:
- Creeping and crawling
- Restless and itching
- Aching and searing
- Tugging and drawing
- Burning and electric
- Current and painful
- Soda pop and worms
- Ants and bugs
- Water flowing and indescribable
What are the ICSD-3 criteria for RLS?
- Criteria A-C must be met for RLS diagnosis.
- A: Urge to move legs with uncomfortable sensations.
- Worsens during rest.
- Relieved by movement.
- Predominantly in evening/night.
- B: Not explained by another condition.
- C: Causes distress or day function impairment.
What genetic and iron-related factors are associated with PLMS?
- Genetic Factor: BTBD-9 gene
- Iron Deficiency: Ferritin < 25 ng/ml found in ~40% of extreme PLMD cases
What conditions need careful exclusion when diagnosing PLMD?
- Depression: a mental health disorder.
- Insufficient sleep syndrome: chronic sleep limitation.
- Circadian changes: disturbances in sleep-wake cycle.
- Obstructive sleep apnea: blocked airway causing disrupted sleep.
What hypothesis related to CVR is associated with PLMS, and what changes occur before PLM?
- Hypothesis (CVR): Not proven yet
- Autonomic Function: Higher
- Heart Rate and Blood Pressure: Increased
- Arousal: ~40% before PLM
What are the diagnostic criteria for PLMD according to AASM 2014?
- PLMI must be greater than 15 per hour.
- Causes clinically significant sleep disturbance or impairment in functioning.
- Symptoms not explained by another disorder, medical or mental.
How is extreme PLMD characterized and detected?
- Characterized by: vigorous sleep behaviors (kicking, punching, gesticulations).
- V-PSG (Video-Polysomnography) detects this via high PLMS index (~60/hr).
- PLMS: periodic limb movements involving whole body, causing arousals.
What are the origins and consequences of PLMS according to the postulated model?
- Origins:
- Spinal Cord Hyperexcitability
- Supraspinal Structures
- Genetics
- Consequences:
- Arousals
- Autonomic Features
- Inflammation
- Vascular Risk
What is the prevalence and clinical relevance of PLMS in the general population without sleep complaints?
- Prevalence of PLMI > 15 is greater than 29%.
- The prevalence increases with age.
- It is often a common incidental finding.
- Lacks apparent clinical relevance.
What should be considered when diagnosing the impact of PLMS on sleep or daytime functioning?
- Assess the reasonable cause-effect relationship.
- Do not diagnose PLMD if the only complaint is of being kicked during sleep.
What improvement occurs with dopaminergic medication in PLMD?
- Enhances day and nighttime complaints.
- Dopaminergic medication is the only drug that effectively suppresses PLMS (Periodic Limb Movements in Sleep).
In what conditions are PLMS found to be aspecific?
- Common in:
- Normal Healthy Persons
- Narcolepsy, RBD, OSA
- Neurodegenerative Disorders: MSA, PD, LBD, MS, Myelopathies, SCA
- ESRF, Iron Deficiency Anemia
- ADHD
- Secondary to Medications: TCA, SSRI
What are the causes and treatments related to iron deficiency in RLS?
- Brain iron deficiency is linked to:
- Ferropenia and related conditions.
- Downregulation of adenosine A1 receptors.
- Treatments:
- Oral or intravenous iron.
- Dipyridamole increases extracellular adenosine and blocks ENT-reuptake mechanisms.
What treatments are used for pediatric Restless Legs Syndrome (RLS) when iron levels are below 50 µg/L?
- Iron levels
How do dopamine and glutamate relate to RLS symptoms?
- Hyperdopaminergic state:
- Increased dopamine in corticostriatal pathways.
- Hyperglutamatergic state:
- Elevated glutamate in corticostriatal pathways.
- Treatments include:
- Selective AMPA-glutamate receptor antagonist Perampanel.
- Alpha-2 delta ligands reduce glutamatergic release.
What is the prevalence and impact of RLS in childhood?
- Prevalence ranges from 1-2%.
- Age-appropriate language helps report symptoms.
- Positive family history and PLMI >5/hr support diagnosis.
- Causes sleep fragmentation.
- Behavioral and educational functioning are mainly impacted.
Which drugs are off-label treatments for pediatric RLS, and what is FDA & EMA's stance?
- No FDA/EMA-approved drugs for pediatric RLS.
- Gabapentin and clonazepam: Used off-label as second-line options.
- Dopaminergic agonists: Restricted to pediatric sleep specialists.
What are the clinical consequences and genetic factors of RLS?
- Clinical consequences:
- Sensitive symptoms (dysaesthesia).
- PLMS (Periodic Limb Movements in Sleep).
- Sleep disturbance and hyperarousability.
- Genetic factors predispose individuals to RLS.
- Dopamine agonists may be involved in treatment.
What are the teratogenic effects of Levodopa/carbidopa when used for restless legs syndrome (RLS) in pregnancy?
- Class: C
- Limited human data
- Levodopa & combinations with carbidopa cause visceral & skeletal malformations in lab animals (rabbits).
How is secondary RLS in children identified and managed when associated with ADHD?
- Secondary RLS: Associated with medications, kidney disease, anemia, neuropathy.
- ADHD presence: Refer to a neurodevelopmental psychiatrist.
- Use gabapentin or clonazepam.
Describe the effects of Pramipexole on pregnancy.
- Class: C
- Dopaminergic medication
- Inhibits prolactin synthesis
- Diminishes lactation
What are the steps for accurately diagnosing RLS/WED in pregnancy?
- Confirm 4 key RLS/WED features.
- Exclude mimics like leg cramps, edema.
- Assess severity: frequency and impact.
- Check for comorbid depression.
How should depression or anxiety associated with pediatric RLS be addressed?
- Assess symptoms: Depression, anxiety.
- Referral: Psychiatrist needed.
- Consider nonpharmacological interventions alongside treatment.
What are some key points about RLS in pregnancy?
- Affects 25% of pregnant women
- First occurs during pregnancy for many
- Severity increases with pregnancy progression
- Symptoms drop/disappear post-delivery
- 3rd most common cause of insomnia during pregnancy
What nonpharmacologic strategies are recommended for RLS/WED during pregnancy?
- Educate about RLS/WED in pregnancy.
- Assess iron status.
- Engage in moderate-intensity exercise.
- Avoid exacerbating factors.
- Consider other interventions.
What are the effects of Clonazepam on pregnant women?
- Class: D
- Causes neonatal withdrawal syndrome if taken late in pregnancy
- Increases risk of birth defects, fetal dependency, floppy baby syndrome after birth
What should be considered during a dopamine drug holiday?
- Duration: Clearly define how long it will last.
- Patient Communication: Thoroughly inform the patient about the process.
- Depression/Anxiety: Be cautious of potential symptoms.
- Psychological Guidance: Provide support if necessary.
- Reality Check: Clarify that it's not an actual "holiday."
- Post-Holiday Steps: Plan for the period after the break.
How is iron status assessed and treated in pregnant women with RLS/WED?
- Check hemoglobin, serum ferritin, iron, TIBC, % saturation.
- Ferritin >75 mcg/L: monitor.
- Ferritin
How does Oxycodone affect pregnancy and newborns?
- Class: B; Class D if chronic use
- Causes neonatal withdrawal syndrome
- Excreted in breast milk
- Causes sedation in newborns
What are the prevention strategies for augmentation in RLS?
- Maintain ferritin levels > 100 µg/l.
- Avoid dopaminergic treatments if possible.
- Use low, slow doses if needed.
- Taper down in positive phases.
- Strive for bearable RLS symptoms.
- Inform the patient.
- Make shared decisions.
What treatments are suggested for refractory RLS/WED in pregnancy?
- Pregnancy: Carbidopa/levodopa, low-dose clonazepam.
- Severe cases: low-dose oxycodone or tramadol.
- Reassess medication periodically and at delivery.
What are the considerations for using Methadone in pregnancy?
- Class: B/C; D if high dosage
- No congenital defects increase
- Risks: low birth weight, neonatal withdrawal, infant death syndrome
- Compatible breastfeeding
What is known about the use of Clonidine in pregnant women?
- Class: C
- Inadequate studies in humans
- Excretion in human milk
What is augmentation in the context of RLS?
- Increase in RLS symptomatology
- Symptoms spread to other body parts
- Earlier onset during the day
- Related to chronic dopaminergic therapy
- Pseudo-progression may lead to incorrect strategies
- After >6 months stable on treatment, clinical situation worsens
What are the treatment strategies for augmentation in RLS?
- Reduce dopaminergic medication gradually.
- Cross-titrate with alternatives:
- Use Alfa 2 delta ligands.
- Consider opioid treatment.
How is RLS/WED managed during lactation?
- Reassess iron status.
- Gabapentin: 300 to 900 mg in the evening/night.
- Low-dose clonazepam if needed.
- Severe cases: Consider low-dose tramadol.
When are opioids considered as a treatment option?
- Used if the 3 first-line medicines did not help.
- Can be used in mono or polytherapy.
How are Folate, Iron, and Magnesium supplements considered during pregnancy?
- Folate: Class A, essential for multivitamin prep.
- Iron: Class A, essential for multivitamin prep.
- Magnesium: Class B, used for eclampsia, beneficial for RLS
What conditions are addressed by Alfa-2-delta ligand?
- Anxiety
- OCD
- Insomnia
- Neuropathic pain
What are the short acting opioid medications and their half-life?
- Short-acting medications (TMax 30–60 minutes):
- Codeine, oxycodone, hydrocodone (T1/2 4 hrs)
- Propoxyphene (T1/2 6 hrs)
What conditions are addressed by Dopaminergica?
- PLMS
- Obesitas
- Cognitive disorders
- Depression/suicidal
- Risk of falling
What are the dosage and pharmacokinetic properties of Gabapentin Enacarbil?
- Dose: 600-1200mg
- Tmax: 5-7 hrs
- T1/2: Stable plasma levels 18-24 hrs, elimination half-life 6 hrs
What are the long acting opioid medications and their half-life?
- Long-acting medications:
- Oxycontin (T1/2 8-10 hrs)
- Methadone (T1/2 16-22 hrs)
- Fentanyl patch (T1/2 72 hrs)
What are the dosage and pharmacokinetic properties of Pregabalin?
- Dose: 25-450mg
- Tmax: 1.5 hrs
- T1/2: Approximately 6 hrs
What are the key characteristics and side effects of dopaminergic drugs?
- Ropinirol
- Dose: 0.25-4 mg
- Tmax: 2-3 hrs
- T1/2: 6 hrs
- Pramipexol
- Dose: 0.125-0.75 mg
- Tmax: 2-3 hrs
- T1/2: 8-12 hrs
- Rotigotine
- Dose: 1-3 mg
- Tmax: 1-3 hrs
- T1/2: 5-7 hrs
- Side effects: OCD and augmentation
What are the dosage and pharmacokinetic properties of Gabapentin?
- Dose: 300-3600mg
- Tmax: 2 hrs
- T1/2: 6-8 hrs
What are key points to consider about oral iron supplementation?
- Absorption is autoregulated by body iron stores.
- Ferrous sulphate 325 mg taken 1-2 times daily with vitamin C.
- 3 months and control serum levels advised.
What are the criteria for iron replacement therapy according to the given data?
- Serum ferritin: < 100 ug/ml
- Transferrin saturation: < 45%
- Serum ferritin > 100 ug/ml: May still respond due to low brain iron despite higher peripheral iron.
When might IV iron be preferred over oral iron?
- Presence of intestinal malabsorption (e.g., celiac disease).
- Previous oral iron treatment failure or intolerance.
- Need for faster response.
- Use of Ferric carboxymaltose (FCM) 1,000 mg in single or divided doses.
What are the key serum tests and treatments involved in iron replacement therapy?
- Serum tests:
- Haemoglobin
- Serum transferrin
- Serum ferritin
- Total iron-binding capacity
- Serum iron
- Transferrin saturation
- Serum CRP
- Treatment criteria:
- Serum ferritin < 100 ug/ml
- Transferrin saturation < 45%
- Patients with serum ferritin > 100 ug/ml may also benefit due to low brain iron.
What are the pharmacological treatments listed?
The following treatments are mentioned:
- Iron replacement therapy
- Dopaminergic agents
- Alfa 2 delta ligands
- Opioids
What are some conservative treatments for insomnia?
- Good sleep hygiene practice.
- Behavioral strategies for alertness.
- Avoid caffeine, nicotine, and alcohol.
- Tactile stimulation via massage or hot baths.
- Exercise programs.
- Less evidence for behavioral therapy than in primary insomnia.
- Comorbid insomnia may use CBT-I, avoid bedtime restriction.
What factors are considered in Step 3 for appropriate treatment of RLS?
Several factors determine appropriate treatment for Restless Legs Syndrome (RLS):
- International RLS severity scale (0-40)
- Frequency of symptoms
- Time-onset RLS complaints
- Effect on sleep and wake cycles
- Comorbidity (important for drug choice)
What are the conservative measures for Restless Legs Syndrome (RLS) according to Step 2?
- Optimal Treatment for Underlying Disorders:
- Iron deficiency: ferritin < 75 µg/l
- Pregnancy
- Renal failure
- Stop or Reduce RLS Inducing Medicine:
- D2 antagonists (metoclopramide, prochlorperazine)
- Traditional antipsychotics (phenothiazines)
- Atypical neuroleptics (olanzapine, risperidone)
- Antidepressants (norepinephrine/SSRIs)
- Sedating antihistamines (diphenhydramine)
- Possibly anticonvulsants (zonisamide, phenytoin, methosuximide)
- Some benzodiazepines (chlordiazepoxide)
What are some known mimics of Restless Legs Syndrome (RLS)?
- Polyneuropathy
- Compression neuropathy
- Akathisia
- ADHD
- Many more (Benes et al, Mov disorders 2007)
What are the steps in the management strategy for RLS?
- Confirm if it's RLS by excluding mimics.
- Address co-morbidities and adjust medications that may worsen or cause RLS.
- Choose treatment based on RLS severity and effectiveness, considering short and long-term outcomes (conservative vs. medication).
What are the co-morbidities or associations with RLS?
- Sleep disorders
- Neurological disorders
- Medical disorders
- Psychiatric disorders
- Drug induced
- Causal effect not always proved
- Multimorbidity is a high-risk factor for RLS (OR 2.5-4.3 vs 1 comorbidity 1.3-1.6)
- Cumulative disease burden is more important
What scales are used to quantify the clinical severity of Restless Legs Syndrome (RLS)?
- International Restless Legs Syndrome Study Group (IRLSSG)
- Self-Completed Restless Legs Syndrome Rating Scale
- Johns Hopkins Restless Legs Severity Scale
- RLS-6 scale
- Quantify clinical severity at a single time point
- Monitor medication effects
What are the steps involved in the diagnosis process mentioned?
- Gather a typical history.
- Conduct a (normal) neurological examination.
- Exclude exacerbating medication.
- Use PSG to identify PLMS.
- Perform EMG.
- Conduct a blood examination.
How do opioid receptor agonists and naloxone affect Restless Legs Syndrome (RLS)?
- Opioid receptor agonists:
- Improve RLS symptoms.
- Naloxone (opiate receptor blocker):
- Exacerbates RLS.
What are the effects of iron deficiency on A1-R cortico striatal regulation?
- Iron deficiency leads to A1-R downregulation in the cortico striatal region.
- Less inhibition on Glu results in increased glutamate release.
- Downregulated A1-R decreases striatal dopamine release.
- Results in less D1-R inhibition.
What hypothesis is suggested regarding central pain processing in Restless Legs Syndrome (RLS)?
- Central pain processing alteration:
- PET studies indicate more severe RLS with higher release of endogenous opioids.
- Post-mortem studies show decreased thalamic p-endorphins.
What are AMPA and NMDA receptors, and how do their inhibitors affect RLS?
- AMPA and NMDA are two glutamate receptors.
- NMDA inhibitors like ketamine and methadone improve RLS.
- AMPA inhibitors such as perampanel also improve RLS.
How does iron deficiency affect medium spiny neurons (MSN)?
- Causes hyperactivation of DIRECT pathway (medium spiny neurons are part of the gabenergic inhibitory cell).
- Leads to inhibition of INDIRECT pathway (output structure is inhibition).
- Final common result: spinal hyperexcitability.
How do opioid agonists function in relation to receptors involved in Restless Legs Syndrome (RLS)?
- Opioid agonists:
- Act on multiple receptors.
- Include histamine, NMDA, and dopamine receptors, besides opioid receptors.
What are the cerebral and spinal regions associated with dopamine?
- Cerebral Regions
- Cortico
- Striatum
- Spinal Regions
- Dorsal-posterior hypothalamus
- A11 region
How do Alfa-2 delta ligands and voltage-gated Ca2+ channels influence RLS?
- Alfa-2 delta ligands affect voltage-gated Ca2+ channels.
- They exert presynaptic inhibition of glutamatergic transmission.
- This action improves RLS symptoms.
Describe the differences in brain conditions with normal and deficient iron levels.
- Normal conditions: Adequate A1-R regulation; balanced Glu and DA activities.
- Iron deficiency: A1-R downregulation, increased Glu release.
- Results in decreased DA levels; indirect MSN inhibition reduced.
What changes occur in the presynaptic hyperdopaminergic state in RLS patients?
- Reduced fluoro-3,4-dihydroxyphenylalanine (f-DOPA) uptake
- Increased tyrosine hydroxylase (TH) staining
- Decreased dopamine transporter
- Increased CSF biopterin and 3-ortho-methyldopa
- Changes in dopamine D2 receptor (D2R) activity
What circuits and pathways are depicted in the diagram related to dopamine?
- Circuits
- Somatic circuits
- Autonomic circuits
- Pathways
- Muscle afferents
- Dorsal horn
- Motoneurons
- Postganglionics
- High threshold
- Low threshold
- NA adrenaline
- SSRIs
- IML
What does the MRI study reveal about glutamate levels in RLS patients?
- MRI studies show increased basal glutamate levels.
- These increases are observed in the thalamus of patients with RLS.
What is the relationship between RLS prevalence and iron availability?
- RLS prevalence is higher with insufficient iron availability.
- Iron-deficient anemia RLS prevalence is 30%.
- This is six times higher than the general population's RLS prevalence.
How does brain iron deficiency in rodents relate to dopaminergic profiles in RLS patients?
- Striatal D2 receptor density decreases
- Dopamine transporter (DAT) reduces
- Phosphorylated tyrosine hydroxylase (TH) expression increases
What are common disease-common variant genetics and their associations?
- Common disease-common variant approach
- Not related to:
- Protein coding
- Candidate genes for RLS (iron metabolism)
- Related to:
- Regulatory regions
- Neurogenesis
- Neuronal differentiation
- Axonal path finding
- Synaptogenesis
Describe brain iron deficiency in the context of RLS.
- Brain iron deficiency includes:
- Reduced CSF ferritin (intracellular iron storage protein).
- Elevated CSF transferrin levels (extracellular iron-carrier protein).
- Normal serum levels of ferritin and transferrin in RLS.
- Substantia nigra and thalamus show low brain iron levels.
What is the heritability percentage and nature of the disorder described in the genetics of pathophysiology?
- Heritability: 50%-60%
- Nature: Familial disease
- Type: Complex multifactorial disorder
- Factors: Genetic and non-genetic susceptibility
What causes a reduction in brain iron in RLS?
- Causes include:
- Epithelial cells of the choroid plexus affect iron transport.
- Reduction of iron ferritin, up-regulation of transferrin receptor.
- Iron transport via transferrin impaired in RLS.
What is the role of PLMS in spinal cord flexor reflex?
- PLMS linked with acute spinal cord injuries.
- No circadian pattern.
- Not associated with cortical micro-arousals.
What are the findings related to GWAS in the context of pathophysiology genetics?
- Risk Loci: MEIS1, BTBD9, PTPRD, MAP2K5, SKOR1, TOX3
- Additional Loci: 13 new risk loci
- Risk Increase: Each variant by ~50%
- Heritability Explained: 19.6%
Describe spinal hyperexcitability and its mechanism.
- Mediated by supraspinal mechanisms.
- Lower threshold of flexor reflex during sleep.
- Leads to spinal cord hyperexcitability.
What are the factors involved in the pathophysiology diagram?
- Iron Deficiency leads to hypo-adenosinergic state and hyper-arousal.
- BID and Genes lead to hyper-glutamatergic and hyper-dopaminergic states.
- Dysfunction of C-S-T-C circuits results in PLMS/Akathisia.
How is sensory-motor integration affected in CSTC circuits?
- TMS: Cortical hyperexcitability, reduced short-latency intra-cortical inhibition.
- fMRI: Striatum, thalamus, frontal regions altered in RLS vs controls.
- Decreased cortical thickness in sensory cortex, corpus callosum.
What are the features to consider for a comprehensive diagnostic assessment of Restless Legs Syndrome?
- Gender
- Age and age of onset
- History of the course of the disease
- Sleep disturbance
- Degree of pain vs discomfort for RLS symptoms
- Parts of the body involved
- Daily pattern of symptoms and activity levels
- History of pregnancy
- History of iron deficiency
What occurs due to enhanced arousal state impairment?
- Impaired neural mechanisms:
- Regulate the arousal-sleep drive.
- Govern sensory motor function.
What are the prevalences of RLS and PLMs in different age groups?
- 20-40 years:
- RLS: ~3%
- PLMs: ~5%
- 40-60 years:
- RLS: ~5%
- PLMs: ~25%
- >60 years:
- RLS: ~10%
- PLMs: ~40%
- PLMs are sensitive but not specific for RLS.
What are the genetic and developmental factors in this pathophysiology?
- Genetically modulated alterations in brain iron homeostasis.
- Developmental abnormalities of the cortico-striato-thalamo-cortical (CSTC) circuit.
- Increased dopaminergic and glutamatergic function.
What are the criteria for leg movement in PLMS according to the AASM?
- Recorded using m. tibialis anterior bilateral surface electrodes.
- Duration: 0.5-10 seconds.
- Onset: 8 µV increase above resting EMG.
- Offset: At least 0.5 seconds, not more than 0.2 µV above resting EMG.
- Excluded: 0.5 seconds before/after respiratory events.
What are the essential criteria for Restless Legs Syndrome?
- Urge to move and dysaesthesias
- Increase at rest
- Relief by movement
- Worse in the evening
- RLS mimic excluded
What defines periodic leg movements (LM) in sleep (PLMS)?
- Requires at least 4 leg movements in a row.
- Interval between movements: 5-90 seconds.
- Association: Arousal and PLM are linked if
What defines chronic persistent and intermittent conditions in this classification?
- Chronic – persistent:
- Occurs when untreated.
- At least 2 times per week over the past year.
- Intermittent:
- Occurs when untreated.
- Less than 2 times per week for the past year.
- At least five lifetime events.
How is the PLM Index calculated?
- Represents the number of periodic leg movements per hour of sleep.
What supportive criteria help diagnose Restless Legs Syndrome?
- Periodic Limb movements in sleep (PLMS)
- Response to dopaminergic medication
- Family history in 1st degree relatives
- Lack of expected daytime sleepiness
What are the diagnostic criteria for Restless Legs Syndrome (RLS)?
Diagnostic criteria for RLS include:
- A: Urge to move & dysaesthesias, increase at rest, relief by movement, worse in the evening.
- B: RLS mimic excluded.
- C: Impact assessment.
What disclosures are included in the presentation by ISMC?
- There are no disclosures listed in the presentation.
- The word "NONE" is used to indicate the absence of any disclosures.
Who presented on Restless Legs Syndrome and PLMS at ISMC 2022?
- Presenter: Roselyne M. Rijsman, MD, PhD
- Affiliation: Sleep Center
- Institution: Haaglanden Medical Center
- Location: The Hague, The Netherlands
- Event: ISMC 2022
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