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Restless Legs Syndrome: A Review

Author/s: 
John W. Winkelman, Benjamin Wipper

Importance Restless legs syndrome (RLS) is a sleep-related movement disorder that affects approximately 3% of US adults to a clinically significant extent and can cause substantial sleep disturbance.

Observations Restless legs syndrome is characterized by an overwhelming urge to move the limbs, typically the legs, often accompanied by unpleasant limb sensations (eg, achiness, tingling). Symptoms, provoked by immobility, are relieved while moving and are typically present or most severe in the evening or at night. Restless legs syndrome symptoms may lead to difficulty falling asleep, staying asleep, or returning to sleep. According to population-based studies, approximately 8% of US adults experience RLS symptoms of any frequency annually and 3% experience moderately or severely distressing symptoms at least twice weekly. Patients with RLS have impaired quality of life and elevated rates of cardiovascular disease (29.6% with coronary artery disease, stroke, or heart failure), depression (30.4%), and suicidal ideation or self-harm (0.35 cases/1000 person-years). Restless legs syndrome is common among patients with multiple sclerosis (27.5%), end-stage kidney disease (24%), and iron deficiency anemia (23.9%); during pregnancy and especially in the third trimester (22%); with peripheral neuropathy (eg, diabetic, idiopathic; 21.5%); and with Parkinson disease (20%). Other risk factors include family history of RLS, northern European descent, female sex (2:1 vs male sex), and older age (RLS prevalence of 10% in adults ≥65 years). Restless legs syndrome is diagnosed based on clinical history; polysomnography is not recommended for diagnosis. Iron supplementation with ferrous sulfate (325-650 mg daily or every other day) or intravenous iron (1000 mg) should be initiated for serum ferritin level less than or equal to 100 ng/mL or transferrin saturation less than 20%. If possible, medications associated with RLS, including serotonergic antidepressants, dopamine antagonists, and centrally acting H1 antihistamines (eg, diphenhydramine), should be discontinued. Gabapentinoids (eg, gabapentin, gabapentin enacarbil, pregabalin) are first-line pharmacologic therapy. In randomized clinical trials, approximately 70% of patients treated with gabapentinoids had much or very much improved RLS symptoms vs approximately 40% with placebo (P < .001). Dopamine agonists (eg, ropinirole, pramipexole, rotigotine) are no longer recommended as first-line medications due to the risk of augmentation, an iatrogenic worsening of RLS symptoms, which has an annual incidence of 7% to 10% with these medications. Patients who do not improve with first-line treatment or have augmented RLS often benefit from low-dose opioids (eg, methadone 5-10 mg daily).

Conclusions and Relevance Restless legs syndrome affects approximately 3% of adults and can have negative effects on sleep and quality of life. Initial management includes cessation of exacerbating medications, as well as iron supplementation for patients with low-normal iron indices. If medication therapy is indicated, gabapentinoids are first-line treatment.

Keywords 
Restless Legs Syndrome sleep quality of life methadone

Approach to pelvic venous disorders

Author/s: 
Andrew D Brown

Objective: To provide a practical guide to help family physicians recognize, diagnose, and manage patients with pelvic venous disorders (PeVDs), often overlooked as causes of chronic pelvic pain and varicose veins.

Sources of information: This review is based on guidelines from the American Venous Forum, the Society for Vascular Surgery, the American Vein and Lymphatic Society, the Society of Interventional Radiology, and the European Society for Vascular Surgery.

Main message: PeVDs are common, though frequently misdiagnosed, causes of chronic pelvic pain and varicose veins predominantly in female patients. These conditions arise from venous reflux or obstruction, which can cause varicose veins and venous hypertension in the renal hilum, pelvis, perineum, and lower extremities. Family physicians should recognize the clinical signs of PeVDs and use appropriate imaging to confirm diagnoses. Interventional treatments, including embolization and stenting, are effective for symptom management and improving patient outcomes.

Conclusion: Early recognition of patients with PeVDs by family physicians is crucial for timely and effective treatment. By using appropriate diagnostic tools and making timely referrals, physicians can substantially improve patients' quality of life.

Keywords 
Perineum female quality of life physicians family Radiology Interventional Varicose Veins Vascular Surgical Procedures hypertension

Restless Legs Syndrome in Adult Primary Care

Author/s: 
Mathur A, Bhat A, Gohar A

Restless Legs Syndrome (RLS) or Willis‑Ekbom Disease is a sensorimotor condition marked by an irresistible need to move the legs, typically accompanied by uncomfortable sensations that peak during periods of rest and disrupt nightly sleep. Early identification in primary care is essential, as timely intervention can dramatically improve the patient's quality of life. Diagnosis relies on a focused clinical history, guided by targeted questions that explore symptom timing, triggers, and relief measures. Management begins with non‑pharmacological strategies, such as optimizing sleep hygiene and correcting iron deficiency, before progressing to pharmacologic options like gabapentinoids or dopamine agonists when needed. By combining lifestyle modifications with tailored medication plans, clinicians can effectively reduce symptoms and improve sleep quality.

Keywords 
Restless Legs Syndrome Dopamine Agonists Sleep Hygiene Sleep Quality Leg quality of life

Canadian guideline for Parkinson disease

Author/s: 
David Grimes, Megan Fitzpatrick, Joyce Gordon, Janis Miyasaki, Edward A Fon, Michael Schlossmacher, Oksana Suchowersky, Alexander Rajput, Anne Louise Lafontaine, Tiago Mestre, Silke Appel-Cresswell, Suneil K Kalia, Kerrie Schoffer, Mateusz Zurowski, Ronald B Postuma, Sean Udow, Susan Fox, Pauline Barbeau, Brian Hutton

KEY POINTS

This guideline update reflects substantial changes in the literature on diagnosis and treatment of Parkinson disease, and adds information on palliative care.

Impulse control disorders can develop in a person with Parkinson disease who is on any dopaminergic therapy at any stage in the disease course, especially for those taking dopamine agonists.

Advanced therapies like deep brain stimulation and intrajejunal levodopa-carbidopa gel infusion are now routinely used in Parkinson disease to manage motor symptoms and fluctuations.

Evidence exists to support early institution of exercise at the time of diagnosis of Parkinson disease, in addition to the clear benefit now shown in those with well-established disease.

Palliative care requirements of people with Parkinson disease should be considered throughout all phases of the disease, which includes an option of medical assistance in dying.

Parkinson disease is chronic and progressive in nature, decreasing the quality of life for both patients with the disease and their caregivers and placing an onerous economic burden on society.1

The first Canadian guideline on Parkinson disease was published in 2012.2 Since that guideline, there have been substantial advances in the literature on the disease, particularly with respect to diagnostic criteria and treatment options. Parkinson Canada undertook to update the existing guideline to reflect these advances, as well as to add information on palliative care.

With the aim of enhancing care for all Canadians with Parkinson disease, this guideline is based on the best published evidence, involves expert consensus when there is a lack of evidence, offers practical clinical advice, takes patient choice and informed decision-making into account and is relevant to the Canadian health care system. The guideline has been divided into 5 main sections to improve the ease of use: communication, diagnosis and progression, treatment, nonmotor features and palliative care. The full guideline is available in Appendix 1, at www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.181504/-/DC1.

Keywords 
Disease Progression Dopamine Agonists exercise therapy palliative care Parkinson Disease quality of life

Clinical practice guideline for management of osteoporosis and fracture prevention in Canada: 2023 update

Author/s: 
Suzanne N. Morin, Sidney Feldman, Larry Funnell, Lora Giangregorio, Sandra Kim, Heather McDonald-Blumer, Nancy Santesso, Rowena Ridout, Wendy Ward

Fracture risk increases with advancing age, as a result of declining skeletal strength and increased risk of falling. In Canada, more than 2 million people live with osteoporosis.1 Every year in Canada, about 150 people per 100 000 suffer a hip fracture, which is considered among the most serious fractures associated with osteoporosis. Fractures lead to increased morbidity, excess mortality, decreased quality of life and loss of autonomy.2 Although osteoporosis is often considered a disease of older females, males are remarkably underevaluated and undertreated for the condition despite suffering worse outcomes following fracture,3 highlighting the importance of providing guidance in males.

Osteoporosis, defined as a bone mineral density (BMD) of 2.5 or more standard deviations below the peak bone mass (i.e., T-score ≤ −2.5), is an indicator of increased fracture risk; this risk is modified by age, sex and other factors.4 A clinical diagnosis of osteoporosis can be made in people aged 50 years and older if they have sustained a low-trauma hip, vertebral, humerus or pelvic fracture after the age of 40 years, or if they have an absolute fracture risk of 20% or more over the next 10 years, using a fracture risk assessment tool (FRAX or the Canadian Association of Radiologists and Osteoporosis Canada [CAROC]).5–7

Advances in risk assessment and nonpharmacologic and pharmacologic management warranted an update to the Osteoporosis Canada 2010 clinical practice guideline for the diagnosis and management of osteoporosis in Canada

Keywords 
quality of life fracture

Diagnosis and management of depression in adolescents

Author/s: 
Korczak, D. J., Westwell-Roper, C., Sassi, R.

Depression is common among adolescents in Canada and has the potential to negatively affect long-term function and quality of life; despite this, in most affected adolescents depression remains undetected and untreated.

Management requires a multimodal approach, including risk assessment, psychoeducation, psychotherapeutic and pharmacologic treatment, and interventions to address contributing factors.

Support from child and adolescent psychiatrists may be required in the case of diagnostic uncertainty and complex presentations, as well as for patients who do not respond to first-line treatments.

Keywords 
depression diagnosis and management adolescents adolescent psychiatry quality of life

A pragmatic approach to the management of menopause

Author/s: 
Lega, I. C., Fine, A., Antoniades, M. L., Jacobson, M.

Menopause is defined as 1 year of amenorrhea caused by
declining ovarian reserve or as the onset of vasomotor
symptoms in people with iatrogenic amenorrhea. It is preceded
by perimenopause or the menopause transition, which can last
for as long as 10 years. Although many treatments exist for
menopausal symptoms, fears around the risks of menopausal
hormone therapy and lack of knowledge regarding treatment
options often impede patients from receiving treatment. In this
review, we summarize the evidence for treating menopausal
symptoms and discuss their risks and benefits to help guide
clinicians to evaluate and treat patients during the menopausal
transition (Box 1).
• Menopausal symptoms can occur for as long as 10 years before
the last menstrual period and are associated with substantial
morbidity and negative impacts on quality of life.
• Menopausal hormone therapy is indicated as first-line
treatment of vasomotor symptoms, and is a safe treatment
option for patients with no contraindications.
• Though less effective, nonhormonal treatments also exist to
treat vasomotor symptoms and sleep disturbances.
• It is critical that clinicians inquire about symptoms during the
menopause transition and discuss treatment options with
their patients.

Keywords 
quality of life menopause risk assessment fear Morbidity

Effect of an Intranasal Corticosteroid on Quality of Life and Local Microbiome in Young Children With Chronic Rhinosinusitis: A Randomized Clinical Trial

Author/s: 
Latek, M., Lacwik, P., Molinska, K., Blauz, A., Lach, J., Rychlik, B., Strapagiel, D., Majak, J., Czech, D., Seweryn, M., Kuna, P., Palczynski, C., Majak, P.

Importance: Intranasal corticosteroids (INCs) remain the first-line treatment of chronic rhinosinusitis (CRS) in both adults and children, despite the lack of evidence regarding their efficacy in the pediatric population. Similarly, their effect on the sinonasal microbiome has not been well documented.

Objective: To assess the clinical, immunological, and microbiological effects of 12 weeks of an INC in young children with CRS.

Design, setting, and participants: This open-label randomized clinical trial was performed in a pediatric allergy outpatient clinic in 2017 and 2018. Children aged 4 to 8 years with CRS diagnosed by a specialist were included. Data were analyzed from January 2022 to June 2022.

Interventions: Patients were randomized to receive intranasal mometasone in an atomizer for 12 weeks (1 application per nostril, once per day) and supplemental 3-mL sodium chloride (NaCl), 0.9%, solution in a nasal nebulizer once a day for 12 weeks (INC group) or 3-mL NaCl, 0.9%, solution in a nasal nebulizer once a day for 12 weeks (control group).

Main outcomes and measures: Measures taken both before and after treatment included the Sinus and Nasal Quality of Life Survey (SN-5), a nasopharynx swab for microbiome analysis by next-generation sequencing methods, and nasal mucosa sampling for occurrence of innate lymphoid cells (ILCs).

Results: Of the 66 children enrolled, 63 completed the study. The mean (SD) age of the cohort was 6.1 (1.3) years; 38 participants (60.3%) were male and 25 (39.7%) were female. The clinical improvement reflected by reduction in SN-5 score was significantly higher in the INC group compared with the control group (INC group score before and after treatment, 3.6 and 3.1, respectively; control group score before and after treatment, 3.4 and 3.8, respectively; mean between-group difference, -0.58; 95% CI, -1.31 to -0.19; P = .009). The INC group had a greater increase in nasopharyngeal microbiome richness and larger decrease in nasal ILC3 abundance compared with the control group. A significant interaction was observed between change in microbiome richness and the INC intervention on the prediction of significant clinical improvement (odds ratio, 1.09; 95% CI, 1.01-1.19; P = .03).

Conclusions and relevance: This randomized clinical trial demonstrated that treatment with an INC improved the quality of life of children with CRS and had a significant effect on increasing sinonasal biodiversity. Although further investigation is needed of the long-term efficacy and safety of INCs, these data may reinforce the recommendation of using INCs as a first-line treatment of CRS in children.

Trial registration: ClinicalTrials.gov Identifier: NCT03011632.

Keywords 
quality of life Lymphocytes Child, Preschool Sodium Chloride / therapeutic use Chronic Disease

Air Quality Index and Childhood Asthma: A Pilot Randomized Clinical Trial Intervention

Author/s: 
Rosser, F. J., Rothenberger, S. D., Han, Y., Forno, E., Celedón, J. C.

Introduction: To reduce air pollution exposure, the U.S. asthma guidelines recommend that children check the Air Quality Index before outdoor activity. Whether adding the Air Quality Index and recommendations to asthma action plans reduces exacerbations and improves control and quality of life in children with asthma is unknown.

Methods: A pilot, unblinded, randomized clinical trial of 40 children with persistent asthma, stratified by age and randomized 1:1, recruited from the University of Pittsburgh Medical Center Children's Hospital of Pittsburgh (Pittsburgh, PA) was conducted. All participants received asthma action plans and Air Quality Index education. The intervention group received printed Air Quality Index information and showed the ability to use AirNow. Asthma exacerbations were assessed through a questionnaire, asthma control was assessed with the Asthma Control Test and Childhood Asthma Control Test, and quality of life was assessed with the Pediatric Asthma Quality of Life Questionnaire. After randomization (July-October 2020), participants were followed monthly for 6 months (exit January-March 2021). Outcome differences between groups were evaluated at the exit visit and over time (analysis was in 2021).

Results: At randomization, there were no significant differences in age, sex, race, or asthma severity. At exit, more intervention participants checked the Air Quality Index (63% vs 15%) with no differences in the proportion of asthma exacerbations or mean Childhood Asthma Control Test or Pediatric Asthma Quality of Life Questionnaire scores. The mean change in Asthma Control Test score was higher in the intervention group (change in Asthma Control Test=2.00 vs 0.15 for the control), which was modified by time (β=1.85, CI=0.09, 3.61). Physical activity was decreased overall and showed modification by treatment and time.

Conclusions: Addition of the Air Quality Index to asthma action plans led to improved asthma control by Asthma Control Test scores but may decrease outdoor activity.

Keywords 
children quality of life asthma air pollution United States
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