Topic 6.3. Restless legs and/or sleep related periodic limb movements
This chapter of the Clinical Management Guidelines for Friedreich Ataxia and the recommendations and best practice statements contained herein were endorsed by the authors and the Friedreich Ataxia Guidelines Panel in 2022.
Topic Contents
6.3 Restless legs and/or sleep related periodic limb movements
6.3.1 Background
6.3.2 Assessment
6.3.3 Diagnosis and management
Disclaimer / Intended Use / Funding
Disclaimer
The Clinical Management Guidelines for Friedreich ataxia (‘Guidelines’) are protected by copyright owned by the authors who contributed to their development or said authors’ assignees.
These Guidelines are systematically developed evidence statements incorporating data from a comprehensive literature review of the most recent studies available (up to the Guidelines submission date) and reviewed according to the Grading of Recommendations, Assessment Development and Evaluations (GRADE) framework © The Grade Working Group.
Guidelines users must seek out the most recent information that might supersede the diagnostic and treatment recommendations contained within these Guidelines and consider local variations in clinical settings, funding and resources that may impact on the implementation of the recommendations set out in these Guidelines.
The authors of these Guidelines disclaim all liability for the accuracy or completeness of the Guidelines, and disclaim all warranties, express or implied to their incorrect use.
Intended Use
These Guidelines are made available as general information only and do not constitute medical advice. These Guidelines are intended to assist qualified healthcare professionals make informed treatment decisions about the care of individuals with Friedreich ataxia. They are not intended as a sole source of guidance in managing issues related to Friedreich ataxia. Rather, they are designed to assist clinicians by providing an evidence-based framework for decision-making.
These Guidelines are not intended to replace clinical judgment and other approaches to diagnosing and managing problems associated with Friedreich ataxia which may be appropriate in specific circumstances. Ultimately, healthcare professionals must make their own treatment decisions on a case-by-case basis, after consultation with their patients, using their clinical judgment, knowledge and expertise.
Guidelines users must not edit or modify the Guidelines in any way – including removing any branding, acknowledgement, authorship or copyright notice.
Funding
The authors of this document gratefully acknowledge the support of the Friedreich Ataxia Research Alliance (FARA). The views and opinions expressed in the Guidelines are solely those of the authors and do not necessarily reflect the official policy or position of FARA.
6.3 Restless legs and/or sleep related periodic limb movements
Sylvia Boesch, Sub Subramony, Mary G. Kearney and Louise Corben
6.3.1 Background
Restless legs and periodic limb movements during sleep are significantly more common in those with FRDA than in the general population: Restless legs syndrome (RLS) has been reported to affect 44.8% of adults with FRDA (14) compared to between 4% and 14% of the general population (15). Moreover, an international multi-center natural history study of people with FRDA found that sleep disturbance was reported by 59% (290/495) of adults and 45% (72/161) of children due to abnormal limb movements or leg cramps (14).
Types of abnormal limb movements
There are several types of abnormal limb movements:
a) Restless legs syndrome (RLS)
b) Periodic limb movements in sleep (PLMS)
c) Flexor spasms
d) Nocturnal leg cramps (NLCs)
RLS and PLMS are the most common types of abnormal limb movements in people with FRDA. It is important that the clinician makes an accurate diagnosis and does not confuse symptoms of RLS with flexor spasms or NLCs.
Restless legs syndrome
RLS is a sensory motor disorder, also known as Willis-Ekbom disorder (WED). It was first described in detail by Swedish neurologist Dr Karl Ekbom in the 1960s.
The symptoms of RLS are uncomfortable and unpleasant sensations in the legs, feet or arms associated with an urge to move them:
a) that are typified by relief of symptoms by moving the affected limb
b) occur during rest in the evening or at night
c) are associated with sleep disturbance or impairment
d) that cannot be explained by any other condition (e.g. arthritis, leg cramps, myalgias) (16).
RLS is a clinical diagnosis based on the above criteria. Given their multiple neurological and systemic issues, questions about symptoms of RLS may not be asked of people with FRDA such that RLS is currently underdiagnosed.
RLS is associated with sleep disturbance, a risk of anxiety or depression, and poorer overall health status. Polysomnography or actigraphy should be carried out in those with FRDA if there is suspicion of a sleep disorder.
Periodic limb movements in sleep
PLMS is repetitive, highly stereotyped limb movements that occur in non-rapid eye movement (non-REM) sleep. Typically, the periodic limb movements (PLMs) are characterized by extension of the big toe, often in combination with partial flexion of the ankle, the knee and sometimes the hip (16). PLMS is assessed using polysomnography, often done overnight in a sleep laboratory, or actigraphy, which uses an accelerometer in a wrist-worn device. Actigraphy has been validated to assess total sleep time and wakefulness after sleep onset (17). PLMs may also occur when the person is awake and they may be more intense.
If the number of PLMs is greater than 15 per hour in adults, or five per hour in a child over the entire night, it is considered pathological and may result in clinically disturbed sleep. PLMS may also cause daytime fatigue.
Note that periodic limb movement disorder (PLMD) is a separate condition and should not be diagnosed in conjunction with RLS. PLMS is seen in 80 to 90% of people with RLS but PLMS is not specific to RLS (18).
The relationship between PLMS and RLS is currently an active field of research (18).
Flexor spasms
Flexor spasms in people with specific disorders (other than FRDA) are typically associated with clinically evident spasticity and brisk reflexes. In FRDA they can occur in the absence of such signs because the peripheral neuropathy associated with FRDA will mask such upper motor neuron signs. Flexor spasms respond poorly to medication which makes them difficult to treat (See Chapter 3.4: Spasticity and Spasms)
Nocturnal leg cramps
NLCs cause a tight, knotted feeling in the legs that usually happens at night. NLCs are similar to spasms but usually last much longer, from several seconds to several minutes. If the cramp is severe, the affected muscle may be sore for days. NLCs are different from RLS and are present in 33% of the general population over 50 years of age.
6.3.2 Assessment
At their annual or biannual review, all individuals with FRDA should:
1) be asked about sleep disturbances and complete the Epworth sleepiness scale, a screening questionnaire for sleep disorders (https://epworthsleepinessscale.com/about-the-ess/)
2) be assessed for spasticity and spasms on physical examination.
6.3.3 Diagnosis and management
There is no evidence supporting specific management strategies for RLS or PLMS in individuals with FRDA. As such, the clinician should adopt general management guidelines for RLS and PLMS (19), with specific considerations for FRDA. In particular, it is critical that accurate diagnosis of RLS and PLMS guide management.
Diagnosis
● A diagnosis of RLS is based on patient history. However, the treating physician must be aware of the specific diagnostic criteria for RLS so they can ask the patient the correct questions. Sleep studies should be undertaken if there is any suspicion of a sleep disorder.
● A low serum ferritin, i.e. < 50 mcg/l may be associated with RLS (20). Therefore, serum ferritin in conjunction with iron studies, hematological and c-reactive protein blood tests should be part of the initial assessment.
● If PLMS is suspected, polysomnography or actigraphy should be done for confirmation of the diagnosis.
● Flexor spasms can be diagnosed from a history taken from the patient or family/carer and can be confirmed by clinical examination, as described above.
● NLC are diagnosed based on an accurate history, bearing in mind they do not usually occur every night.
Treatment of RLS
As RLS may be caused or precipitated by medication, an initial review of the person’s current medication should be undertaken, specifically asking about selective serotonin reuptake inhibitors (SSRI), tricyclics, lithium and metoclopramide, as well as some hypnotic agents, before any treatment is recommended (21).
Regular physical activity, sleep hygiene, regular hours for going to bed, avoiding the use of electronic devices in bed and reducing or avoiding caffeine, smoking and alcohol should be recommended. A review of non-pharmacological treatments for RLS reported some evidence for clinically significant effects from exercise, acupuncture, pneumatic compression devices and near infrared light (21). Up to 65% of patients with RLS regularly use alternative approaches for symptom relief (21). We suggest that non-pharmacological therapy for RLS should be tried first, especially for milder cases, before proceeding to pharmacological therapy.
If iron levels are found to be low, iron supplements may be trialed (22). However, as mitochondrial iron overload can play a role in FRDA pathogenesis, patients who are given iron supplements should be followed up with frequent reassessment of their iron and ataxia status and discontinuation of iron if ferritin reaches acceptable levels.
If correctly diagnosed, RLS responds to pharmacological treatment. Gabapentin and pregabalin are currently the preferred pharmacological choice (19). L-dopa and the dopamine agonists pramipexole and ropinirole are only recommended for occasional use in RLS due to the high risk of augmentation, characterized by an increase in the severity of RLS. These drugs can cause RLS to come on earlier in the day and have a faster onset when at rest, cause symptoms to spread to the upper limbs and trunk, and are associated with a shorter duration of the effect of treatment. Therefore, the calcium channel blockers gabapentin and pregabalin are the preferred options.
Treatment of PLMS
PLMS may be a clinical symptom of RLS and should be treated if the individual has disabling symptoms. Dopaminergic drugs such as levodopa and dopamine agonists pramipexole and ropinirole are recommended. A positive response to these medications may help confirm the diagnosis.
Prevention/lifestyle
QUESTION: Should prevention/lifestyle versus none or medication be used for individuals with restless legs syndrome (RLS) symptoms with Friedreich ataxia?
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RECOMMENDATION: We conditionally recommend the use of prevention strategies/lifestyle changes (such as reduction of alcohol and nicotine use) over no prevention strategies/lifestyle changes or medication in individuals with Friedreich ataxia with RLS.
JUSTIFICATION: RLS is a significant problem affecting 44.8% of adults with Friedreich ataxia. Lifestyle interventions such as a reduction of alcohol and nicotine especially in the evening may have an impact on RLS symptoms in general. Weighing up the balance between benefits, harms and costs, these measures appear to be acceptable. Regular physical activity, sleep hygiene, a regular time for going to bed, avoiding caffeine and the use of electronic devices in bed are likely to help RLS.
SUBGROUP CONSIDERATION: This recommendation is for individuals with Friedreich ataxia with symptoms of RLS. There is less known about prevention of RLS in children.
Evidence to Recommendation Table PDFChecking serum ferritin
QUESTION: Should serum ferritin levels be checked versus no checking be used for individuals reporting restless legs syndrome (RLS) with Friedreich ataxia?
[sg_popup id=”587″ event=”click”][/sg_popup]STRENGTH OF RECOMMENDATION: ↑
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RECOMMENDATION: We conditionally recommend investigating serum ferritin levels in individuals with Friedreich ataxia presenting with symptoms of RLS over not checking ferritin.
Serum ferritin is usually measured in combination with serum iron and transferrin saturation. Given that serum ferritin can be raised when inflammation is present, acute and chronic inflammation should be assessed at the same time by doing a white cell count and measuring C-reactive protein (CRP).
JUSTIFICATION: Research shows that serum ferritin levels are often low in those with RLS. Prior to testing serum ferritin levels, it is important to make sure that the individual with Friedreich ataxia fulfils the criteria for RLS. For a non-movement disorder neurologist, flexor spasms and RLS are easily confused. In fact, an individual may even report that they have RLS when in fact they have flexor spasm.
SUBGROUP CONSIDERATION: This recommendation is for individuals with Friedreich ataxia with symptoms of RLS. Restless legs are more common in those who have sleep disturbances. Females are generally more prone to have low ferritin levels than males.
Evidence to Recommendation Table PDFComplementary/alternative treatments
QUESTION: Should complementary/alternative treatments versus none or medication or lifestyle or physiotherapy be used for individuals with restless legs syndrome (RLS) symptoms with Friedreich ataxia?
[sg_popup id=”587″ event=”click”][/sg_popup]STRENGTH OF RECOMMENDATION: ↓
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RECOMMENDATION: We suggest alternative/complementary treatments should not be used over no treatment/medication/lifestyle/physiotherapy for RLS in Friedreich ataxia.
JUSTIFICATION: Based on no published evidence on complementary/alternative treatments in Friedreich ataxia, we suggest that regular physical activity, sleep hygiene, regular hours for going to bed, avoiding caffeine before bed and the use of electronic devices in bed may assist in managing RLS. A review of current medication is also suggested, which should focus in particular on selective serotonin reuptake inhibitors (SSRI), tricyclics and metoclopramide.
RLS is a significant problem affecting 44.8% of adults with Friedreich ataxia. Complementary/alternative treatments may have undesirable side-effects for a person with Friedreich ataxia. There is no RCT on the use of complementary/ alternative treatments on RLS in Friedreich ataxia. However, if there are no undesirable side-effects, some people with RLS may find alternative treatments as helpful as medication and without the known side-effects of medication.
It should be borne in mind when recommending any complementary/alternative treatments that they may be expensive and private insurers may not cover the cost for a person with Friedreich ataxia.
SUBGROUP CONSIDERATION: This recommendation is for individuals with Friedreich ataxia with symptoms of RLS. Restless legs are more common in those who have sleep disturbances.
Evidence to Recommendation Table PDFIron supplementation
QUESTION: Should iron supplementation versus no supplementation be used for individuals with restless legs syndrome (RLS) and serum ferritin < 50 mcg/ml with Friedreich ataxia?
[sg_popup id=”587″ event=”click”][/sg_popup]STRENGTH OF RECOMMENDATION: ↑
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RECOMMENDATION: We suggest iron supplementation could be trialed for treatment of RLS in individuals with Friedreich ataxia and serum ferritin < 50 mcg/ml, but only If other treatments have been tried and are not effective. Clinicians should only consider a trial of iron supplements if serum ferritin is < 50 mcg/ml and no acute or chronic inflammation is present, with close monitoring and a review to assess any adverse effects on ataxia after 3 to 6 months. If an individual has RLS and serum ferritin > 75 mcg/ml, they should not be given iron supplements.
JUSTIFICATION: RLS is a significant problem affecting 44.8% of adults with Friedreich ataxia. Internationally, the recommendation for the treatment of RLS in the general population is to give iron supplements if ferritin is below 50-75 mcg/ml. However, in Friedreich ataxia, the pathophysiology of iron is not clear with iron overload in the mitochondria of cells and iron deficiency in the cytoplasm. Although there is currently no strong evidence, it is thought that iron supplementation may make ataxia worse. Therefore, we recommend that alternative treatments be given before iron is used to treat RLS.
There have been no RCTs of iron supplementation to treat RLS in those with Friedreich ataxia. A survey on iron supplementation in RLS from expert clinicians involved in the care of those with Friedreich ataxia could not reach a consensus on this question. From the survey of 24 clinicians, 15 could not provide any information, one reported that iron did harm and six reported a small benefit. Therefore, the benefits of iron supplementation in the case of true iron deficiency with symptoms need to be considered against the side effects of iron supplementation. Due to the possibility of pathophysiological iron overload in the mitochondria in Friedreich ataxia, excess iron should be avoided.
As RLS can interfere with the quality of sleep, it is an important symptom and effective treatment is desirable. However, the theoretical possibility of making ataxia worse in people with Friedreich ataxia is an important consideration.
SUBGROUP CONSIDERATION: This recommendation is for individuals with Friedreich ataxia with symptoms of RLS. Restless legs are more common in those who have sleep disturbances.
Evidence to Recommendation Table PDFOral medication
QUESTION: Should oral medication versus none be used for individuals with idiopathic restless legs syndrome (RLS)/periodic limb movements in sleep (PLMS) with Friedreich ataxia?
[sg_popup id=”587″ event=”click”][/sg_popup]STRENGTH OF RECOMMENDATION: ↑
[sg_popup id=”658″ event=”click”][/sg_popup]LEVEL OF EVIDENCE: ⨁◯◯◯
RECOMMENDATION: We conditionally recommend medication for individuals with Friedreich ataxia with RLS which interferes with sleep (with or without associated PLMS) over no medication.
Gabapentin and pregabalin are the preferred choice of pharmacological treatment of RLS in Friedreich ataxia as they are as effective as levodopa but do not have the same side-effects. The dopamine agonists pramipexole and ropinirole may be helpful but should be used with caution in Friedreich ataxia due to the risk of augmentation of RLS symptoms. If PLMS is present it should be treated if the individual has disabling symptoms. Levodopa may be used intermittently when disabling RLS/PLMS symptoms are present since augmentation of RLS occurs only with long-term use. Given that levodopa alleviates symptoms of RLS rapidly, a ‘test dose’ of levodopa may be used to confirm a diagnosis of RLS in an individual with Friedreich ataxia.
JUSTIFICATION: RLS is a significant problem affecting 44.8% of adults with Friedreich ataxia. However, there is uncertainty or variability in the opinion expressed about the value of medication to treat RLS. There are no RCTs addressing the impact of vitamins, baclofen, opioids or dopaminergic drugs, L-Dopa on sleep quantity/sleep benefit, impact on behavior, cognition, mood, degree of pain versus discomfort, or HRQOL in individuals with Friedreich ataxia with RLS.
A survey of experts in Friedreich ataxia showed that the majority, 16 out of 24 clinicians, had no opinion or expertise in using these medications. Of those who had, 6 out of 8 clinicians, found that L-dopa had a modest effect on RLS. However, L-dopa can cause the undesirable side effect of augmentation which is where there is an increase in severity of RLS, faster onset of symptoms at rest, earlier onset of symptoms during the day, the symptoms spread to the upper limbs and trunk and shortened duration of treatment effect. Vitamin supplementation, baclofen and opioids and other dopaminergic drugs are of limited value in the treatment of restless legs in Friedreich ataxia.
SUBGROUP CONSIDERATION: This recommendation is for individuals with Friedreich ataxia with symptoms of RLS/PLMS. There is greater clinical experience with using medication for RLS in adults than children; therefore, even more caution needs to be exercised when prescribing medication for children.
Evidence to Recommendation Table PDFLay summary of clinical recommendations for restless legs syndrome and/or periodic limb movements in sleep in Friedreich ataxia
Restless legs syndrome (RLS) and periodic limb movements in sleep (PLMS) are five times more common in those with Friedreich ataxia than in the general population.
Restless legs syndrome
The key symptoms of RLS are an overwhelming urge to move the legs, typically late in the day while resting, such as in bed before sleeping, that is often but not always associated with uncomfortable or unpleasant sensations in the legs. These symptoms can be relieved by moving the legs or walking. This can lead to disturbed sleep. The symptoms cannot be accounted for by other medical conditions such as leg swelling, muscle aches, arthritis or habitual foot tapping.
Periodic limb movements in sleep
PLMS are spontaneous, repeated, jerky movements, usually of the leg, which occur during sleep. They often interfere with sleep and cause fatigue and sleepiness during the day. The presence of PLMS is confirmed by doing a sleep recording called polysomnography. This is usually done in a sleep laboratory where the individual spends the night. More recently it has been done with an actigraphy, which uses an accelerometer in a device on the wrist. Both devices record muscle contraction in the lower leg while sleeping. PLMS are found in 4 out of 5 people with RLS.
Why these recommendations?
It is not known why individuals with Friedreich ataxia experience RLS and PLMS more than other people and there have not been specific guidelines to help people with Friedreich ataxia manage RLS or PLMS. Based on some research and our clinical experience, we recommend the following assessments and treatments for people with Friedreich ataxia and restless legs:
● The physician that cares for your Friedreich ataxia should explore symptoms of RLS during your visits.
● A healthy lifestyle, including reducing alcohol and smoking, regular physical activity, regular hours for going to bed, and avoiding caffeine and electronic devices before sleep may help with RLS.
● A full blood count (FBC) and serum ferritin in conjunction with iron studies and C reactive protein (CRP) should be taken since abnormal values of these chemicals may be seen in RLS and correcting them may relieve the symptoms of RLS.
● All your current medications to be checked, to see if the symptoms may be linked to a medication you are taking. Anti-depressants of the types known as selective serotonin reuptake inhibitors (SSRI) or tricyclics, lithium, the anti-sickness tablet metoclopramide and some sleeping tablets are known to cause RLS.
● Some medications may help RLS that interferes with sleep. Gabapentin and pregabalin are currently the preferred choice of medication. Oral iron should be used with caution and only started if serum ferritin is less than 50 mcg/ml. Dopaminergic drugs are not recommended for RLS – although they may help the symptoms at first, they may make the symptoms significantly worse in the long-term.
What does this mean for you as a person living with Friedreich ataxia or caring for someone living with Friedreich ataxia?
It might be important for you to speak with your Friedreich ataxia healthcare professional if you are experiencing difficulties sleeping or have unexplained daytime fatigue or sleepiness. A healthy lifestyle with good sleep hygiene is recommended for those with Friedreich ataxia to try to avoid RLS and/or PLMs.
Who is this recommendation specifically for?
People with Friedreich ataxia who are experiencing restless legs before going to bed, sleep difficulties or unexplained fatigue.
Sylvia Boesch, MD, MSc
Head, Center for Rare Movement Disorders Innsbruck, Department of Neurology, Medical University Innsbruck, Innsbruck, Austria
Email: sylvia.boesch@i-med.ac.at
Louise Corben, PhD
Principal Research Fellow, Murdoch Children’s Research Institute, Melbourne, Victoria, Australia
Email: louise.corben@mcri.edu.au
Mary G. Kearney, MD
Neurology Research Fellow, Tallaght University Hospital, Dunlavin, Wicklow, Ireland
Email: marykearney@gmail.com
Sub H. Subramony, MD
Professor of Neurology and Pediatrics, University of Florida College of Medicine, Gainesville, Florida, USA
Email: s.subramony@neurology.ufl.edu
2. Birnkrant DJ, Bushby K, Bann CM, Alman BA, Apkon SD, Blackwell A, et al. Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management. Lancet Neurol. 2018;17(4):347-61.
3. Buu MC. Respiratory complications, management and treatments for neuromuscular disease in children. Curr Opin Pediatr. 2017;29(3):326-33.
4. Sheehan DW, Birnkrant DJ, Benditt JO, Eagle M, Finder JD, Kissel J, et al. Respiratory management of the patient with Duchenne muscular dystrophy. Pediatrics. 2018;142(Suppl 2):S62-S71.
5. Boentert M, Cao M, Mass D, De Mattia E, Falcier E, Goncalves M, et al. Consensus-based care recommendations for pulmonologists treating adults with myotonic dystrophy type 1. Respiration. 2020;99(4):360-8.
6. Tsou AY, Paulsen EK, Lagedrost SJ, Perlman SL, Mathews KD, Wilmot GR, et al. Mortality in Friedreich ataxia. J Neurol Sci. 2011;307:46-9.
7. Silva IS, Pedrosa R, Azevedo IG, Forbes AM, Fregonezi GA, Dourado Junior ME, et al. Respiratory muscle training in children and adults with neuromuscular disease. Cochrane Database Syst Rev. 2019;9:CD011711.
8. Williamson E, Pederson N, Rawson H, Daniel T. The effect of inspiratory muscle training on Duchenne muscular dystrophy: a meta-analysis. Pediatr Phys Ther. 2019;31(4):323-30.
9. Botez MI, Mayer P, Bellemare F, Couture J. Can we treat respiratory failure in Friedreich ataxia? Arch Neurol. 1997;54(8):1030-3.
10. Manni R, Tartara A, Marchioni E, Piccolo G. Polygraphic sleep patterns in heredoataxia: a study of nine cases. Revue d Electroencephalographie et de Neurophysiologie Clinique. 1986;16(2):117-21.
11. Corben LA, Ho M, Copland J, Tai G, Delatycki MB. Increased prevalence of sleep-disordered breathing in Friedreich ataxia. Neurology. 2013;81(1):46-51.
12. Patterson A, Almeida L, Monari E, et al. Sleep and fatigue in Friedreich ataxia. IARC Meeting; Pisa, Italy 2018.
13. Annane D, Orlikowski D, Chevret S. Nocturnal mechanical ventilation for chronic hypoventilation in patients with neuromuscular and chest wall disorders. Cochrane Database Syst Rev. 2014(12):CD001941.
14. Lynch D. FA Clinical Outcome Measures (FA-COMS) Registry (unpublished data): clinicaltrials.gov; 2017 [Available from: https://clinicaltrials.gov/ct2/show/NCT03090789
15. Ohayon MM, O’Hara R, Vitiello MV. Epidemiology of restless legs syndrome: a synthesis of the literature. Sleep Med Rev. 2012;16(4):283-95.
16. American Academy of Sleep Medicine. International classification of sleep disorders. Westchester, IL: American Academy of Sleep Medicine; 2014.
17. Marino M, Li Y, Rueschman MN, Winkelman JW, Ellenbogen JM, Solet JM, et al. Measuring sleep: accuracy, sensitivity, and specificity of wrist actigraphy compared to polysomnography. Sleep. 2013;36(11):1747-55.
18. Fulda S. The Role of Periodic Limb Movements During Sleep in Restless Legs Syndrome: A Selective Update. Sleep Med Clin. 2015;10(3):241-8, xii.
19. Winkelmann J, Allen RP, Hogl B, Inoue Y, Oertel W, Salminen AV, et al. Treatment of restless legs syndrome: Evidence-based review and implications for clinical practice (Revised 2017). Mov Disord. 2018;33(7):1077-91.
20. Frauscher B, Hering S, Hogl B, Gschliesser V, Ulmer H, Poewe W, et al. Restless legs syndrome in Friedreich ataxia: a polysomnographic study. Mov Disord. 2011;26(2):302-6.
21. Bega D, Malkani R. Alternative treatment of restless legs syndrome: an overview of the evidence for mind-body interventions, lifestyle interventions, and neutraceuticals. Sleep Med. 2016;17:99-105.
22. Trotti LM, Becker LA. Iron for the treatment of restless legs syndrome. Cochrane Database Syst Rev. 2019;1:CD007834.
These Guidelines are systematically developed evidence statements incorporating data from a comprehensive literature review of the most recent studies available (up to the Guidelines submission date) and reviewed according to the Grading of Recommendations, Assessment Development and Evaluations (GRADE) framework © The Grade Working Group.
This chapter of the Clinical Management Guidelines for Friedreich Ataxia and the recommendations and best practice statements contained herein were endorsed by the authors and the Friedreich Ataxia Guidelines Panel in 2022.
It is our expectation that going forward individual topics can be updated in real-time in response to new evidence versus a re-evaluation and update of all topics simultaneously.