​Kembara Xtra - Medicine - Periodic Limb Movement Disorder

​Kembara Xtra - Medicine - Periodic Limb Movement Disorder 
Periodic limb movements while sleeping (PLMS) along with considerable sleep disruption and/or functional impairment during the day:  Evidence of periodic limb movements during sleep (PLMS) during polysomnography PLMS are tibialis anterior muscle contractions that happen repeatedly, mostly during non-rapid eye movement (NREM) sleep.
Movements include rhythmical big toe extension and ankle dorsiflexion, either unilaterally or bilaterally, simultaneously or not.
Occasionally, knee and hip flexion is seen.
Less frequently, people move their arms or make more broad motions.
Unbeknownst to the patient, movements may be linked to cortical arousals from sleep (PLMs with arousals—PLMA).
The diagnosis requires a clinical history of substantial sleep disruption and/or functional impairment.
Insomnia, unrestorative sleep, daytime tiredness, and somnolence are some of the complaints.
The patient's bed mate could gripe about their motions.
The PLMS cannot be explained by other sleep disorders such obstructive sleep apnea (OSA), narcolepsy, or restless legs syndrome.
If there is concomitant sensory perception or restlessness, the diagnosis is not PLMD but may instead be restless leg syndrome (RLS). No related restlessness or dysesthesia while awake.
 Nervous and musculoskeletal systems are both affected  Other names for the PLMS include nocturnal myoclonus and sleep myoclonus. 

Prevention Incidence
PLMD is uncommon and affects both adults and children (1).
More than 15% of people with insomnia have PLMS.
PLMS are common in OSA, narcolepsy, and while starting CPAP.
Prevalence
Age-related increases in PLMS 45 percent of patients over 65 display PLMS > 5/hr but not PLMD.
PLMD is substantially less frequent; 85% of RLS patients have PLMS, which is underdiagnosed in 5% of adults.


Pathophysiology and Etiology 
Understudied; the majority of data on PLMS as it relates to RLS states: - Increased incidence of PLMS in untreated Parkinson disease (PD) and lower incidence of PLMS in schizophrenia support CNS dopamine dysregulation.
 Exacerbating and triggering factors: - Renal failure - Arthritis - Peripheral neuropathy
Spinal cord damage and pregnancy
 Negative consequences of medication:
- Lithium and the majority of antidepressants (but not bupropion or desipramine); - Some antipsychotic and antidementia drugs
- Dopaminergic antiemetics
Antihistamines that are sedative
RLS patients without PLMS but those with BTBD9 on chromosome 6p are genetically related with PLMS.

Risk factors include a history of premature birth, an iron shortage and related illnesses, and a family history of RLS.

Prevention: Encourage enough sleep and steer clear of PLMS causes such iron deficiency, which is typically seen in young children.


Accompanying Conditions 

End-stage renal disease, cardiovascular disease, stroke, narcolepsy, and gastric surgery
 Peripheral neuropathy Insomnia, insufficient sleep, parasomnias Pregnancy Arthritis Lumbar spine disease; spinal cord injury  ADHD, worry, and oppositional behavior Child Safety Considerations
PLMD may exist for years before overt RLS.
 RLS is more frequently associated with.
 Relationship and differential diagnosis with rising pain, oppositional behaviors, mood disorders, and restless sleep disorder

 Pregnancy considerations: Usually goes away after delivery; may be linked to iron or folate insufficiency; most severe in the third trimester
Aspects of Geriatrics
 PLMS may raise the incidence of atrial fibrillation in the elderly. May cause or exacerbate circadian disruption and "sundowning"

Diagnosis 
Insomnia, which is the inability to stay asleep, nonrestorative sleep, daytime exhaustion, and somnolence, as well as oppositional behaviors, memory impairment, depression, and ADHD, especially in children, are all symptoms of disturbed sleep.

clinical assessment 
No particular findings


Multiple Diagnoses 

PLMS associated with RLS, RBD, or narcolepsy are not PLMD; rather, they are related to the sleep disease.
PLMS that coexists with OSA may be linked to respiratory complications but is not PLMD.
Sleep-related leg cramps are isolated, painful, and muscle knots. Fragmentary myoclonus is characterized by 75 to 150 ms of electromyographic (EMG) activity, minimal movement, and no periodicity. Sleep beginnings are nonperiodic, widespread, and only occur at wake-sleep transition.  Fasciculations and tremor: no sleep relationship Nocturnal seizures: epileptiform EEG, motor pattern incongruent with PLMs  Sleep-related rhythmic movement disorder (SLRMD): voluntary movement during the wake-sleep transition that occurs more frequently than PLMs Restless sleep disorder (RSD): big, irregular bodily motions 

Laboratory Results 
Polysomnography (PSG) exhibiting PLMS: EMG amplitude rise >8 V from baseline Tibialis ant EMG activation lasting 0.5′′ to 10.0′′ A series of four movements take place every five to ninety seconds.
 Correlated with alterations in heart rate brought on by autonomic level arousals The majority of PLMs events start within the first NREM sleep cycles.
Variability in PLMS from night to night is typical.

Initial examinations (lab, imaging)

ferritin, transferrin, iron-binding capability, and other serum iron storage 

Tests in the Future & Special Considerations
If there is a suspected change or the patient is not responding to treatment, check iron reserves, at least ferritin. Other diagnostic procedures, such as EMGs and, if necessary, nerve conduction tests for peripheral neuropathy and radiculopathy Children's PLMSI >5/hr and adults' PLMSI >15/hr in the PSG test

Similar to the RLS treatment paradigm, but all drugs are used for PLMD off-label.

General Actions 
Assess iron deficiency and address it; get enough sleep each night; engage in regular, low-impact activity in the evening; and use a weighted blanket to warm the legs (or long socks, leg warmers, an electric blanket, etc.). Pre-bedtime warm soaks and hot/leg baths are recommended. Avoid caffeine and alcohol.

Use the bare minimal effective dose of medication.
Medication objectives include: - Improving perceived sleep quality.
- Manage PLMS and how they affect slumber.
Consider the dangers, side effects, and interactions in various populations (such as the use of benzodiazepines in geriatric patients).
Treatment should reduce daytime sleepiness.

Initial Line
Dopamine agonists decrease PLMS, improve sleep quality, but have no impact on irregular sleep patterns; start low and titrate gradually to the recommended amount.
- Pramipexole, brand name Mirapex: 0.125 to 0.5 mg; titrate by 0.125 mg; take 2 hours HS
Ropinirole (Requip): 0.25 to 4.00 mg; titrate by 0.25 mg; take half an hour to one hour after a meal; preferable in renal impairment - Transdermal rotigotine (Neupro): 1 to 3 mg/24 hr patch; start at 1 mg/24 hr and gradually increase to 3 mg for maximum impact.
Avoid dopamine agonists in psychotic patients, especially if they are also taking dopamine antagonists, as they may have a stimulant impact that makes it more difficult to fall asleep.

Next Line
Voltage-gated calcium channel 2 subunit ligands: beneficial for related neuropathy; reduce PLMS and enhance sleep architecture; use cautiously with renal impairment. Gabapentin enacarbil (Horizant): 600 mg early evening.
Benzodiazepines and agonists, most frequently used for its ability to promote sleep; use with caution in the elderly - Clonazepam (Klonopin): 0.5 to 2.0 mg QHS - Zaleplon, zolpidem, temazepam, triazolam, alprazolam, diazepam


Referrals to movement disorders, neurology, and sleep medicine clinics include the following:
 Sx getting worse while taking medicine Uncontrolled symptoms in adults and specific populations due to intractable iron insufficiency
Child Safety Considerations
First-line therapy: non-pharmacologic Determine and remedy an iron deficit.
0.1 to 0.3 mg of low-dose clonidine may be used; orthostatic hypotension should be avoided.

pregnant women's issues
Initial strategy: nonpharmacological treatments and iron supplements (5) Refractory PLMD—may take oxycodone in the second and third trimesters: Stop 2 weeks before birth. Clonazepam 0.25 to 1 mg QHS. CarbiDOPA/levoDOPA 25/100 to 50/200 ER.
Aspects of Geriatrics
Avoid giving weak or fragile individuals any medications that could make them woozy or unsteady.


Furthermore Treated 

If iron is lacking, take 325 mg of ferrous sulfate and 200 mg of vitamin C between meals. BID or the complete dose QD - Repletion may take several months of therapy.
0.05 to 0.30 mg/day of clonidine; minimal data; Relaxis leg vibration device. 

Surgical Techniques 

correction of peripheral vascular, neuropathic, or orthopedic issues 

Alternative Medicine 
Supplements with vitamins and minerals, such as calcium, magnesium, vitamin D, vitamin B12, and folate, may be beneficial.

Patient Follow-Up Monitoring
Until the condition is stable, assess the severity of the symptoms, the adverse effects of the drug, and any augmentation.
A repeat iron blood test should be done if it was previously low.

Diet 
Avoid alcohol and caffeine, especially late in the day.


Primary PLMD has no known cure and is prognosed to be lifelong. Secondary PLMD may improve if the underlying cause(s), such as inadequate iron reserves, are treated. Current treatments typically manage symptoms, and PLMD frequently occurs before the onset of RLS.

Complications 
Tolerance to medications needing higher doses Increased PLMs, sleep disruption, and the onset of RLS are all effects of dopamine agonists. - Risk rises with higher doses.
- Anemia raises the chance of augmentation.
Iatrogenic PLMD (from antidepressants, etc.) - Add alternative medication and then progressively reduce dopaminergic drug.