​Kembara Xtra - Medicine - Restless Leg Syndrome

​Kembara Xtra - Medicine - Restless Leg Syndrome 
Sensorimotor dysfunction, which is characterized by a powerful, almost insurmountable need to move the limbs. Usually, legs are afflicted first, although arms or other body parts may be affected as well.
The following signs (Sx):
- Start or get worse while you're at rest or inactive
- Recur with inactivity but are eased by movement. If not right now, previous relief from movement - Preferably at night or in the evening. Previously reported circadian aspect if not current Leg jerks recorded while awake or asleep.
Early (age 45) versus late (age >45) onset - Phenotype with early onset: Rapid progression is prevalent; familial, stable, slow development of Sx is present in 40–92% of cases; late start phenotype has higher aggravating variables.
A similar term is Willis-Ekbom illness. 

Epidemiology 

Parous females are twice as likely to have the condition as parous males. Incidence: 0.8-2.2% annually; onset: any age.
Temperature (cold temperatures and other environmental conditions may cause or enhance the occurrence of Sx) 


Prevalence

One to three percent of Caucasians (likely underdiagnosed) Lower in non-Caucasians (excluding Koreans) and increases with age 


Pregnant women's issues
10–30% prevalence; causes or aggravates RLS
Predictors include prior history (Hx), family history (Hx), iron deficiency (ID), and Hgb 11 g/dL. The majority of cases are relieved by one month after delivery.

Pathophysiology and Etiology 

 Brain iron insufficiency (BID), which results in CNS dopamine dysregulation due to either low serum iron levels or poor iron transport into the brain: - Dopamine (DA) levels that are higher than usual in the morning and lower than usual at night cause the D2 receptors for DA to be downregulated. - Hyperarousal and sleeplessness caused by an increase in glutamate and a reduction in adenosine; anomalies in the sensorimotor pathways and an increase in motor excitability brought on by extended immobility, such as hospitalizations;
Medically induced:
- All but bupropion antidepressants
- Antiemetics with DA blockers (such as metoclopramide and prochlorperazine); - Antipsychotics with phenothiazines (such as risperidone, clozapine, olanzapine, quetiapine, etc.).
One possible exception is the partial D2 agonist aripiprazole. Memantine, other xanthines including theophylline, and other drugs that improve cognition
sedating antihistamines, over-the-counter cold remedies

Genetics: 2p14, 2q, 6p21.2, 9p, 12q, 14q, 15q23, and 20p susceptibility loci; MEIS1, MAP2K5/LBXCOR1, BTBD9, PRPRD, and TOX3 genes

Risk factors include family history, chronic renal failure, sleep deprivation, alcohol use, and caffeine (limited data). ID: ferritin levels below 75 ng/mL or transferrin saturation (TSAT) below 16, respectively. 

Prevention 
Regular exercise and physical activity during the day, followed by low-impact nighttime activities like stretches and walks.  Get enough sleep, and if you can, put off getting up.
Avoid these substances primarily in the evening.
 Steer clear of drugs that could cause RLS.


Accompanying Conditions 

Parkinson disease, multiple sclerosis, peripheral neuropathy, Machado-Joseph disease, migraine, insomnia, sleep walking, delayed sleep phase, iron deficiency, renal disease/uremia/dialysis, gastric surgery, IBS, liver disease, anxiety, depression, ADHD, cardiovascular disease, coronary artery disease, and stroke. Orthopedic issues, arthritis, and fibromyalgia; venous insufficiency/peripheral vascular illness; pulmonary hypertension; lung transplantation; chronic obstructive pulmonary disease (COPD); 

Clinical, Hx-based diagnosis that is "difficult to describe"
For an RLS diagnosis, each requirement must be satisfied: - A compulsion to move one's legs, generally accompanied by or believed to be brought on by uncomfortable and unpleasant leg feelings. The urge must: Start or get worse when you're resting or inactive, as when you're lying down or sitting  Be eased partially or completely by motion, such as stretching or walking, at least during the duration of the activity. Even if relief from movement might not be apparent, it must have been previously documented.
 Take place solely or primarily at night or in the evening as opposed to during the day. Even if the circadian feature might not be apparent, it must have been previously noted.
- The aforementioned characteristics are not simply explained by "mimics" or other sleep, health, or behavioral issues. Leg cramps, uncomfortable positions, repetitive foot tapping, arthralgias/arthritis, myalgias, leg edema, peripheral neuropathy, and radiculopathy are examples of mimics, however some of these conditions may coexist. - RLS symptoms can lead to anxiety or discomfort, sleep disruption, or impairment in one or more areas of functioning, including mental, physical, social, occupational, educational, behavioral, or another.

History: 35% of patients report pain.
Examples of such symptoms include: antsy, burning, achy, itchy, and "can't get comfortable." The sole "discomfort" may be the want to move.
Some patients need to get up and move around.
- 80% of patients have PLMS
- Insomnia, exhaustion, worry, and sadness
 Range in severity: from infrequent, slight issue to daily, mild to moderate, to severe impact on quality of life 

Child Safety Considerations
PLMS, RLS in close biological relatives, and insomnia or sleep disturbance are additional results that are supportive.

Clinical evaluations are often normal.

Multiple Diagnoses 
Vascular compression: A simple posture shift can relieve discomfort without the need for repeated motions.
Claudication: Moving doesn't make the ache go away.
Peripheral neuropathy: prominent daytime component unresponsive to dopamine agonists (DAs); Motor neuron disease fasciculation/tremor: no discomfort or circadian pattern; Dermatitis/pruritus: movement only to scratch; no circadian pattern; Sleep-related leg cramps: presence of muscle knot; PLMD: no waketime urge to move; Growing pains: no urge to move or relief by movement

Laboratory Results Serum iron reserves are evaluated using ferritin, TSAT, iron-binding capacity, and serum iron.


Other/Diagnostic Procedures

The diagnosis is supported by frequent PLM during wakefulness and before going to sleep, as well as frequent PLMS on sleep study (PSG) data.
Suggested immobilization test (SIT) or multiple immobilization test (m-SIT) performed prior to or in addition to nocturnal PSG
- The patient tries to remain motionless in bed for one hour (SIT) or four one-hour periods every two hours (m-SIT), while filling out a VAS or m-SIT disturbance scale every ten minutes.
- RLS may be present if SIT >40 movements per hour.


Management 
If you need more iron, take 325 milligrams of FeSO4 in the evening along with 100 mg of vitamin C.
- Repletion is not complete until serum ferritin is above 75 ng/mL and TSAT is above 16%.
 Daily exercise; stay away from things that make RLS worse.
Avoid aggravating influences and get regular rest.
Hot baths, warm soaks, and leg massages are all recommended. In bed, use a weighted blanket and long socks. Obstructive sleep apnea (OSA) should be treated if it is present.  Extensive mental exercise (puzzles, games, etc.)

Medication 
Consider delaying the use of drugs in mild to moderate instances until all other options have been exhausted. Use the lowest effective dose to manage Sx, including sleep disruption.
 Determine the severity of Sx at every interaction using a scale such the John Hopkins (JHRLSS), IRLS, or sIRLS.
 Select choices with extended acting times.
Refractory RLS could need a mix of treatments.


Initial Line

Anticonvulsants are more efficacious and less likely to cause augmentation in patients who are DA-naive. - 300 to 1,200 mg of gabapentin enacarbil (Horizant) per day by 5:00 PM
50 to 450 mg of pregabalin (Lyrica) per day (off-label)
- Off-label dosage of 100 to 2,400 mg/day for gabapentin (Neurontin)
Every meeting with DA: Examine your impulse control disorders (ICD) and augmentation.
- Pramipexole (Mirapex): titrate by 0.125 mg every 4 days; take 0.125 to 0.5 mg 1 to 2 hours prior to Sx.
- A tablet of pramipexole ER 0.375 mg
- Ropinirole (Requip): titrate by 0.25 mg every 4 days from 0.25 to 4.0 mg 30–1 hour before Sx.
- 2 mg of ropinirole XL
Transdermal rotigotine (Neupro): Start at 1 mg/d; titrate by 1 mg/wk.
Avoid DAs in people with psychosis, especially if you're also taking dopamine antagonists.
Don't go beyond the DA-recommended dose.


Next Line
Off-label: Benzodiazepines and agonists, insomnia/anxiety; buprenorphine naloxone 20/0.5 QD-BID Temazepam, triazolam, alprazolam, zaleplon, zolpidem, and diazepam are short-acting DAs for sporadic symptoms. Carbidopa/levodopa (Sinemet or Sinemet CR): 10/100 to 25/250; PRN up to twice per week. Clonazepam (Klonopin): 0.5 to 3.0 mg/day.

Pregnant women's issues
Initial strategy: nonpharmacological treatments, evaluate/correct ID
 Steer clear of drugs in classes C or D.
If severe and the aforementioned treatments fail in the third trimester, low-dose clonazepam, clonidine, carbidopa/levodopa, or opioids may be an option. 

Child Safety Considerations

 Nonpharmacologic therapies, good sleep hygiene, and determining and treating iron deficiency are the first-line treatments. For sleep, think about low-dose, age-appropriate gabapentin, clonidine, and melatonin.
Aspects of Geriatrics
Avoid taking drugs that make you woozy or unsteady because many drugs might aggravate or start RLS in elderly people.

Referral 
severe, persistent symptoms


Further Therapies 

Clonidine: 0.05 to 0.10 mg/day; Baclofen: 20 to 80 mg/day; vitamin and mineral supplements: Ca, Mg, D, B12, folate;

Orthopedic, neuropathic, or lower extremity vein disease surgical procedures (laser ablation, sclerotherapy)

Alternative Therapies 
Compression stockings, enhanced external counterpulsation, Relaxis leg vibration device (FDA-approved), pneumatic leg compression devices, yoga, acupuncture, and MicroVas treatment.

Admission 
Long-term hospitalization can cause or exacerbate RLS.

Patient Follow-Up 
Monitoring
If taking iron, reassess iron reserves, at least ferritin, at 1- to 4-week intervals until stable and thereafter once a year. If status changes, evaluate for augmentation, ICD, concomitant conditions, and medications.
DIET Steer clear of alcohol and caffeine, especially in the evening.


Early onset: a chronic, incurable condition with no known cure; late onset/secondary: a chronic, progressive disorder that may go away with the elimination of precipitating events. Current therapies often manage symptoms.

Complications The presence of worsening symptoms after DA therapy should be monitored at each visit: - Sx spread to different body areas or have a stronger intensity. Sx may also progress by 2 to 4 hours with a shorter latency during rest.
- Risk increases with dose, and Sx gets worse as dose increases.
- Higher risk when using medications with shorter half-lives
- A lack of iron raises danger.
- Decrease dosage and stop using DAs for at least 10 days; add an alternative medicine or continue treatment beyond that. Every time a patient receiving DA receives a visit, the possibility of ICD/Sx must be considered.
Iatrogenic RLS (occurring after blood donation or loss)

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