RLS is characterized by the irresistible urge to move the legs when at rest or while trying to fall asleep. RLS prevalence in the general population has been estimated to be approximately 5 % . high in women

2. Restless Leg Syndrome
MODERATOR – Dr. Sumit Khattri(H.O.D.)
Dr. Mohan Dhyani
(Associate Professor)
By Dr Rashi Agarwal (PG-2)

3. RLS also known as
Willis-Ekbom disease

4. • RLS is a neurologic disorder presenting with
sensory-motor symptoms, usually creepy or
crawling sensations in the extremities
characterized by the irresistible urge to move
the legs when at rest or while trying to fall
asleep.

5. The patient-
• feels an initial or worsening urge to move the legs
during rest or inactivity
• feels some or total relief of the sensation when
moving the legs
• feels these urges more (or only) in the evening or at
night compared with during the day.
• The symptoms -produce significant distress or
impairment; cannot be explained another medical,
psychiatric, or medical condition; and are not drug
(or substance) related.

6. • Hirshkowitz M., Sharafkhaneh A, In Ch 23 Sleep Disorders in Sadock B.J. , Sadock V.A. , Ruiz P. ,
Comprehensive Textbook of Psychiatry, 10th edition Walters Kluwer Pvt Ltd;2017

8. The International Restless Legs
Syndrome Study Group (IRLSSG)
• Diagnosis can be made if all of the five criteria are met:
• A need to move the legs, usually accompanied or caused by
uncomfortable, unpleasant sensations in the legs: Any kind of sensation
may be a manifestation of RLS and a wide variety of descriptions have
been used ranging from "painful" to "burning" - some people say it feels
like they have insects inside their legs or arms. Sometimes the need to
move is present without the uncomfortable sensations and sometimes the
arms or other body parts are involved in addition to the legs.
• The need to move and unpleasant sensations are exclusively present or
worsen during periods of rest or inactivity such as lying or sitting.
• The need to move and unpleasant sensations are partially or totally
relieved by movement such as walking or stretching at least as long as the
activity continues.
• The need to move and unpleasant sensations are generally worse or
exclusively occur in the evening or night.
• Symptoms are not solely accounted for by another condition such as leg
cramps, positional discomfort, leg swelling or arthritis

9. Two different RLS phenotypes of RLS
have been reported:
• (1) Early-onset idiopathic RLS, the most frequent
form, with a prevalence onset around 20–40
years, very frequent RLS familial history, slow
disease progression, and low cerebrospinal fluid
(CSF) ferritin level.
• (2) Late-onset RLS with the onset after 40 years of
age, less frequent RLS familial history, more rapid
disease evolution, and more frequent association
with other diseases, such as renal failure,
diabetes, anemia, neuropathy, and myelopathy

10. Epidemiology
• RLS prevalence in the general population has
been estimated to be approximately 5 % . A
large population study showed a prevalence of
any restless symptoms to be 7.2%, and
moderately or severely distressing symptoms
to be 2.7%

11. Factors
• Sex-Prevalence is about twice as high in
women as in men.
• Age- RLS is generally a condition of middle to
old age, but at least one-third of patients
experience their first symptoms before the
age of 20 years
• Prevalence- increases with age
• Family history-frequently in those who
experience early symptoms.

12. • RLS can even
affect a phantom
limb

14. • Pregnancy- RLS is the most common
movement disorder occurring during
pregnancy. It develops more frequently during
the third trimester and disappears within the
first month after delivery in most cases.

15. • It is common during pregnancy, affecting
approximately one in five pregnant women in
Western countries. Many report moderate or
severe symptoms and negative impact on sleep.
• The disease was strongly related to the third
trimester of pregnancy and tended to disappear
reaching the time of delivery. Affected women
presented lower values of hemoglobin and mean
corpuscular volume compared with healthy
subjects

16. Circadian rhythm-
• Studies showed that the severity of leg
discomfort followed a circadian rhythm with a
maximum occurring after midnight. The
circadian pattern in the occurrence of RLS
symptoms has been investigated by using a
method called the “Suggested Immobilization
Test” (SIT), administered every 2–4 h during
24–28 h.

18. Childhood RLS
IT is often misdiagnosed as growing pains, limiting
access to appropriate treatment. ferritin, a
measure of iron storage, should be routinely
assessed in children with RLS. Oral iron
supplementation should be considered for ferritin
below <50 mcg/L
An abnormal dopaminergic system may be
responsible for the association between RLS and
ADHD; approximately one-quarter of individuals
with RLS have attention problems and conversely,
13% to 35% of individuals with ADHD meet
criteria for RLS.

19. • Most patients report difficulty falling asleep,
but some patients fall asleep rapidly and wake
up shortly after with unpleasant legs
sensations that force them to get up and walk
around also awakening the partner

20. Genetics
• Several loci have been found on chromosomes
12q, 14q, 9p, 2q, 20p
• Linkage on 12q seemed the best defined and
has been designated RLS1, on 14q for a few
families and has been designated RLS2 , on
9p24–22 has been designated RLS3

21. • Association of gene variants BTBD9, MEIS1,
MAP2K5/LBXCOR, and PTPRD with RLS has been found
and replicated, indicating a genetic substrate upon which
environmental factors might act.
• Single nucleotide polymorphism- BTBD9 is estimated to
confer a population attributable risk (PAR) of 50 % for RLS.
Together, all account for 70 % of the PAR for RLS in
individuals with European ancestry.

22. For children, iron supplementation and
nonpharmacologic treatments are indicated for mild
cases. Moderate to severe cases should be referred for
medication trials in the setting of long-term specialty
care.
The incidence is high in children aged between 8-18
years with iron deficiency, or iron deficiency anemia,
or both. This finding supports the importance of iron
replacement therapy especially during the growth and
development of children.
• Restless legs and peripheral movement disorders BV DOI: 10.1016/B978-1-4377-2369-4.00023-2011 Elsevier Ltd, Inc, 8

23. Picchietti DL, Bruni O, de Weerd A, et al.: Pediatric restless legs syndrome diagnostic criteria: an update by the International Restless Legs Syndrome Study
Group. SleepMed14(12):1253–1259,2013.
Picchietti MA, Picchietti DL: Advances in pediatric restless legs syndrome: iron,genetics, diagnosis and treatment. Sleep Med 11(7):643–651.
Halac G.et. al. , The relationship between Willis-Ekbom disease and serum ferritin levels among children in Northwestern Turkey Neurosciences 2015; Vol. 20 )
• For children, iron supplementation and
nonpharmacologic treatments are indicated for
mild cases. Moderate to severe cases should be
referred for medication trials in the setting of
long-term specialty care
• The incidence is high in children aged between 8-
18 years with iron deficiency, or iron deficiency
anemia, or both. This finding supports the
importance of iron replacement therapy
especially during the growth and development of
children.

24. Mimics
• Akathisia
• Arthralgias/arthritis
• Panic attacks
• Painful legs.
• Leg cramps,
• Positional discomfort,
• Myalgias, leg edema
• Habitual foot tapping
• Polyneuropathies, radiculopathy,
• Meralgia paraesthetica
• Sleep onset myoclonus and nocturnal myoclonus

25. Periodic limb movements of sleep
(PLM or PLMS)
• Brief repetitive
movements
• Mostly of legs
• Occur every 20-40
seconds.
• Often present in RLS
patients
• Initial jerk followed by
tonic spasm.
• Dorsiflexion of big toe,
foot and even leg
• Occurs during stage I and
II of sleep

26. Conditions with increased occurrence
of restless legs syndrome
Iron deficiency, Uremia, Pregnancy
Medications -serotonergic/norepinephrine
agents, dopamine receptor antagonists
antihistamines
Medical conditions: Celiac disease, Crohn’s
disease, Rheumatoid arthritis, Fibromyalgia
diabetes
Psychiatric conditions-Anxiety, Depression

27. Pathology and Pathophysiology-
• The pathophysiology of RLS is still unclear but various
studies have linked RLS to several neurological factors
like to iron and dopamine metabolism. Iron is a
cofactor for tyrosine hydroxylase, which is essential for
dopamine synthesis.
• Neuropathological studies showed marked decreases
in iron, ferritin heavy chain, transferrin receptor, and
iron transport proteins contrasting with normal ferritin
light chain and tyrosine hydroxylase in the substantia
nigra of RLS patients.
• Connor JR, Wang XS, Patton SM, Enzies SL, Troncoso JC, Earley CJ, Allen RP. Decreased transferring receptor expression by
neuromelanin cells in restless legs syndrome. Neurology. 2004;62:1563–7

28. • Ref: Nagatsu, T. & Nagatsu, I. J Neural Transm (2016) 123: 1255. https://doi.org/10.1007/s00702-
016-1596-4

29. Work up
• Detailed history and physical examination are
important part of RLS workup.
• The International Restless Legs Syndrome
Study Group (IRLS) Rating Scale a ten-item
self-administered scale, has become the gold
standard to measure severity and impact of
RLS in clinical trials

30. • There are no investigations to confirm the diagnosis of
restless legs syndrome (RLS).Test for 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.
• Basic organ functions, chemistry, and thyroid hormone
levels. Needle electromyography and nerve conduction
studies to differentiate from signs of nerve problems
like neuropathy

32. Suggested Immobilisation Test
• It looks at electromyelogram reading and
discomfort ratings of a subject asked to lie still
for an hour during the daytime. In RLS the
subject will have significantly higher levels of
discomfort and restlessness than normal
subjects.

33. POLYSOMNOGRAPHY
• Records PLMS
• Correlates strongly but indirectly with RLS
• Useful measure for diagnosing RLS and
monitoring of treatment.
• Tibialis anterior muscle-recorded PLM scoring-
pathological value >five PLM/hour of sleep.
• Evidence of arousal.

35. Management
• Pharmacological therapy should be limited to those
patients who suffer from clinically relevant RLS
symptoms including intermittent RLS with impaired
sleep quality or quality of life
• Agents used to treat RLS include dopamine precursors
(e.g., levodopa)
• The dopaminergic agonists pramipexole, rotigotine
and ropinirole are FDA approved and represent the
treatment of choice.
• Antiepileptic drugs α-2-δ ligands, including gabapentin,
gabapentin enacarbil, and pregabalin.
• Sometimes the alpha-2 agonist clonidine is also used.

37. Augmentation
• Dopaminergic drugs can specifically worsen
overall disease severity from pretreatment levels
through a process called augmentation. An
increase in the severity of symptoms, a shift in
time for the start of symptoms to earlier in the
day, a shorter latency to symptoms when resting,
and sometimes spread of symptoms to other
body parts.
• Increase of dopamine concentration in the CNS
with dopaminergic overstimulation, particularly
of the D1 receptor.

38. PREVENTING AUGMENTATION-
The most effective preventive strategy involves reducing
the dopaminergic load by using the lowest effective
dose
First‐line treatment of de novo patients- therapeutic trial
with alpha‐2‐delta ligands (i.e. gabapentin enacarbil,
pregabalin), as these are alternative, effective first‐line
treatment forRLS without risk of augmentation
Intermittent (non‐daily) treatment of RLS/WED to
prevent augmentation- Levodopa may be used for
intermittent treatment at most two to three times a
week.
Using longer acting dopamine agonists
Dose reduction
Switching to an alternate dopaminergic agent

39. TREATMENT OF AUGMENTATION
• Elimination of exacerbating factors -The patient’s serum
ferritin level should be measured, and, if the concentration
is < 50‐75 μg/L, or if transferrin saturation is less than 20%,
supplementation with orally administered iron is
recommended unless poorly tolerated or contraindicated.
Intravenous (IV) iron can also be considered.
• It is important to ask the patient about any lifestyle
changes (sleep deprivation, alcohol use, decreased
mobility), or changes in medical factors (use of dopamine‐
antagonists, antihistamines or antidepressants, recent
opioid discontinuation, blood loss), that can contribute to
an earlier onset or an increase in the severity of RLS/WED
symptoms.

40. Mild symptoms of augmentation-
• Dopaminergic monotherapy is at a total daily
dose at or below maximum recommended
levels
• Continue current dopamine agonist therapy,
• Complete switch- an α2δ calcium‐channel
ligand (pregabalin, gabapentin enacarbil),
rotigotine
• Severe augmentation

41. Coping and support
• RLS/WED is generally a lifelong condition. Living with RLS/WED involves
developing coping strategies that work for you, such as:
• Tell others about your condition. Sharing information about RLS/WED will
help your family members, friends and co-workers better understand
when they see you pacing the halls, standing at the back of the theater or
walking to the water cooler many times throughout the day.
• Don't resist your need for movement. If you attempt to suppress the urge
to move, you may find that your symptoms worsen.
• Keep a sleep diary. Keep track of the medications and strategies that help
or hinder your battle with RLS/WED, and share this information with your
doctor.
• Stretch and massage. Begin and end your day with stretching exercises or
gentle massage.
• Seek help. Support groups bring together family members and people
with RLS/WED. By participating in a group, your insights not only can help
you but also may help someone else.

42. Lifestyle and home remedies
• Making simple lifestyle changes can help alleviate symptoms of
RLS/WED:
• Try baths and massages. Soaking in a warm bath and massaging
your legs can relax your muscles.
• Apply warm or cool packs. Use of heat or cold, or alternating use of
the two, may lessen your limb sensations.
• Establish good sleep hygiene. Fatigue tends to worsen symptoms of
RLS/WED, so it's important that you practice good sleep hygiene.
Ideally, have a cool, quiet, comfortable sleeping environment; go to
bed and rise at the same time daily; and get adequate sleep.
• Exercise. Getting moderate, regular exercise may relieve symptoms
of RLS/WED, but overdoing it or working out too late in the day may
intensify symptoms.
• Avoid caffeine. Sometimes cutting back on caffeine may help
restless legs. Try to avoid caffeine-containing products, including
chocolate and caffeinated beverages, such as coffee, tea and soft
drinks, for a few weeks to see if this helps.

43. rTMS
• High-frequency rTMS can markedly alleviate the
motor system symptoms, sleep disturbances, and
anxiety in RLS patients. These results suggest that
rTMS might be an option for treating RLS.

44. THANK YOU