Secondary RLS and comorbidities

Synthesis of the evidence on RLS/Willis-Ekbom disease arising alongside, or apparently secondary to, other medical conditions: chronic kidney disease/dialysis/transplant, pregnancy, iron-deficiency anemia, peripheral neuropathy, Parkinson disease, multiple sclerosis, ADHD, depression/anxiety, insomnia, cardiovascular disease/hypertension, diabetes, venous insufficiency, sleep apnea, migraine, and rheumatic/autoimmune disease. All claims below cite a study note filename (in knowledge-base/studies/) or a PMID. Medical disclaimer: nothing here is individual medical advice; treating any underlying comorbidity, and any change to dopamine-agonist or alpha-2-delta-ligand dosing, must be done only under physician supervision and never by stopping a medication abruptly (dopamine agonist withdrawal syndrome, DAWS, can be severe).

What is established (grade A/B)

• Chronic kidney disease/dialysis carries markedly elevated RLS prevalence (15-30% versus 5-10% in the general population per a systematic review; 2023-safarpour-ckd-rls-systematic-review.md), corroborated by a 2026 JAMA clinical review citing 24% prevalence in end-stage kidney disease (2026-winkelman-rls-jama-clinical-review.md, PMID 41563785) and by modality-stratified data showing 51.7% in hemodialysis, 40.7% in peritoneal dialysis, 26.2% in conservatively managed CKD, and only 23.8% in post-transplant patients (2025-elangovan-ckd-dialysis-iron-prevalence.md).
• Kidney transplantation can produce complete, durable remission of CKD-associated RLS: in an 11-patient case series, RLS resolved in 100% of patients within 1-21 days of transplant, and recurred rapidly (within 10 days to 2 months) if the graft failed (2002-winkelmann-kidney-transplant-reverses-rls.md) - among the strongest evidence in this knowledge base that treating an underlying comorbidity, not RLS itself, can eliminate symptoms.
• Pregnancy is a very high-prevalence RLS state: a meta-analysis of 27 studies (51,717 subjects) found pooled prevalence of 21% overall, rising by trimester (8%/16%/22%) and falling to 4% postpartum (2018-chen-pregnancy-prevalence-meta-analysis.md); a large prospective cohort found 26% prevalence at any antenatal visit and 34.7% cumulative incidence, with prior depression and family history as risk factors (2026-hackethal-life-on-pregnancy-rls-cohort.md, pre-existing).
• Multiple sclerosis: a meta-analysis of 75 studies (15,411 patients) found pooled RLS prevalence of 28% (vs 8% in controls), higher in women (30%) than men (22%) (2022-zali-meta-analysis-multiple-sclerosis-rls.md); comorbid RLS significantly worsens anxiety and depression scores in MS (2022-sevim-ms-rls-anxiety-depression.md).
• Migraine: a meta-analysis of 15 studies found pooled RLS prevalence of 17.0% in migraineurs versus 7.0% in non-migraineurs, with a stronger association in case-control (OR 3.77) than cross-sectional (OR 1.25) designs (2019-wang-migraine-meta-analysis.md).
• Rheumatic/autoimmune disease: a meta-analysis of 17 studies (2,406 patients) found RLS prevalence of 26.6% in rheumatoid arthritis, 32.5% in lupus, 38.1% in fibromyalgia, and 30.8% in ankylosing spondylitis (2023-padhan-meta-analysis-rheumatic-diseases-rls.md); celiac disease independently shows 31% RLS prevalence versus 4% in matched controls (2010-moccia-celiac-rls-prevalence.md, pre-existing).
• Cardiovascular risk factors are consistently elevated in RLS at the population level: a 9-study meta-analysis found a pooled hypertension OR of 1.36 (2017-shen-meta-analysis-hypertension-risk.md, pre-existing), and a PLMS-focused meta-analysis found elevated coronary artery disease (OR 1.57) and cardiovascular disease (OR 1.28) comorbidity (2018-huang-plms-cardiovascular-meta-analysis.md, pre-existing); a large physician cohort (n=22,786) found diabetes (OR 1.41) and prior stroke (OR 1.40) as RLS correlates (2013-winter-vascular-risk-factors-rls-men.md).
• Diabetes: prevalence of RLS in type 2 diabetes is 28.3% (33.3% women, 20.6% men), rising with diabetes duration (p=0.025) and insulin use (p=0.035), and remaining elevated (17.1%) even without other RLS comorbidities (2018-akin-type2-diabetes-rls-prevalence.md).
• Peripheral neuropathy: RLS occurs in 30% of a general polyneuropathy clinic cohort, preferentially in small-fiber, acquired/dysimmune neuropathy rather than large-fiber axonal disease (2006-gemignani-polyneuropathy-rls.md, pre-existing; diabetic-neuropathy-specific data in 2007-gemignani-diabetic-neuropathy-rls.md, pre-existing).
• Parkinson disease: a very large German case-control study (138,345 PD cases, 276,690 controls) found RLS strongly associated with subsequent PD diagnosis (OR 4.19), including when RLS preceded PD by 5-10 years (OR 3.73), identifying RLS as a genuine prodromal feature, not only a PD-era comorbidity (2023-schrag-parkinson-prodromal-risk-factors.md).
• Psychiatric comorbidity is substantial and clinically serious: population-based data show RLS severity correlates with anxiety (r=0.21) and depression (r=0.20) severity (2004-sevim-population-anxiety-depression-rls.md), and a large US claims cohort (169,373 people) found RLS independently associated with more than double the risk of subsequent suicide or self-harm (adjusted HR 2.66, rising to 4.14 after excluding depression/insomnia/OSA) (2019-zhuang-suicide-self-harm-risk-rls.md).
• Sleep apnea overlaps substantially with RLS: a 707-patient cohort found 16.1% comorbid RLS in OSA, with paradoxically lower RLS severity at higher apnea severity (2024-kim-osa-rls-depression-insomnia.md); a PRISMA-guided systematic review of 10 studies (>3,000 patients) confirmed 10-30% prevalence and found CPAP reduced RLS medication need in >70% of patients in some cohorts (2025-tam-co-rosa-systematic-review.md).
• Venous insufficiency: in a screened vein-clinic population, 22% had RLS, and sclerotherapy produced 98% initial symptom relief (recurrence 8%/28% at 1/2 years) (1995-kanter-sclerotherapy-varicose-veins-rls.md); an independent cohort found endovenous laser ablation plus foam sclerotherapy reduced mean IRLS severity by ~80% (26.9 to 5.5) (2008-hayes-endovenous-laser-ablation-rls.md).

Emerging C

• Iron-deficiency anemia outside CKD/pregnancy carries a very high RLS rate: 41.1% in women diagnosed with iron deficiency anemia at an internal medicine clinic, described by the authors as an 8-10 fold increase over general-population estimates (2016-kolukisa-iron-deficiency-anemia-rls-prevalence.md); CKD-specific iron indices are significantly worse in CKD patients with RLS than without (lower ferritin/TSAT/serum iron, higher TIBC, all p<0.01) (2025-elangovan-ckd-dialysis-iron-prevalence.md).
• ADHD-RLS overlap extends across the lifespan: pediatric prevalence ranges 11-54% across 9 studies (2025-ghayad-systematic-review-adhd-pediatric-rls.md, pre-existing), and in adults RLS occurs in 33% of ADHD patients, with iron deficiency in 35.5% (higher still in the RLS+ subgroup), suggesting a shared iron/dopamine-linked neurodevelopmental endophenotype (2019-lopez-adult-adhd-iron-deficiency-rls.md).
• Fibromyalgia-specific cohort data (64% RLS prevalence, worse sleep/daytime sleepiness with comorbid RLS) run notably higher than the Padhan 2022 meta-analytic pooled estimate (38.1%), suggesting real heterogeneity across fibromyalgia populations/diagnostic methods that is not yet resolved (2008-stehlik-fibromyalgia-rls-prevalence.md).
• CBT-for-insomnia (CBTI) meaningfully improves sleep in RLS patients with comorbid insomnia (4 sessions vs a single sleep-hygiene session), with benefits maintained to 3 months, though from a small trial (2020-song-cbti-rls-comorbid-insomnia-rct.md, pre-existing).
• Genome-wide polygenic risk scoring extends epidemiological obesity/smoking/alcohol associations with RLS risk, implying partly shared genetic liability rather than purely behavioral confounding (2020-didriksen-gwas-three-novel-variants.md, pre-existing); a prospective lifestyle cohort separately found normal weight, physical activity, and non-smoking each independently lower RLS risk (2016-batool-anwar-lifestyle-factors-cohort.md, pre-existing).
• Obesity itself associates with RLS: a case-control comparison of 143 obese (mean BMI 36.8) versus 94 non-obese (mean BMI 25.7) adults found RLS presence correlated with obesity and vascular risk factors, and obese participants had significantly higher depression, anxiety, and insomnia scores than non-obese participants, though the abstract did not report exact RLS prevalence percentages (2017-yildiz-obesity-risk-factor-rls.md).
• A large US veteran cohort found very large associations between incident RLS and subsequent mortality (HR 1.88), coronary heart disease (HR 3.97), stroke (HR 3.89), and incident CKD (HR 3.17) (2016-molnar-veterans-cohort-mortality-comorbidity.md, pre-existing) - treat as an upper-bound, hypothesis- generating estimate (see Contested section) rather than a precise risk figure.

Contested or negative findings

• After adjusting for confounders, a meta-analysis of 8 studies (644,506 patients) found RLS was NOT independently associated with cerebrovascular or cardiovascular events, only with all-cause mortality (HR 1.52) - directly contradicting a naive "RLS causes heart attacks/strokes" narrative and standing in tension with the much larger unadjusted effect sizes in the Molnar 2016 veterans cohort above (2017-katsanos-meta-analysis-cardiovascular-mortality.md, pre-existing).
• A Korean clinical cohort (n=1,163) found periodic limb movements during sleep were NOT associated with hypertension, contesting the population-level hypertension association reported elsewhere (2018-shin-plms-hypertension-negative.md, pre-existing).
• In celiac disease, RLS was NOT significantly correlated with gluten-free diet adherence or with routine iron-metabolism markers, even though hemoglobin was lower in celiac patients with RLS - complicating a simple "just correct the iron" narrative for this specific comorbidity (2010-moccia-celiac-rls-prevalence.md, pre-existing).
• Prior myocardial infarction was associated with LOWER (not higher) RLS odds (OR 0.73) in a large physician cohort, the opposite direction from prior stroke (OR 1.40) in the same study, illustrating that "cardiovascular disease" is not a uniform RLS risk direction across different vascular events (2013-winter-vascular-risk-factors-rls-men.md).
• A small Bosnian survey (n=120) found RLS in 30% of hypertensive and 30% of hypertensive-plus-diabetic patients but only 21% of diabetes-only patients, with the diabetes-only-versus-control difference not reaching significance (p=0.107) despite hypertension comparisons being significant - a caution against assuming diabetes alone (without hypertension) always shows a significant, replicable RLS association in small samples (PMID 27147785, no dedicated note; confirmed via PubMed metadata, not written up as a full study note per this knowledge base's duplication/thoroughness threshold).
• Fibromyalgia RLS-prevalence estimates range from 38.1% (17-study meta-analysis) to 64% (single 332-patient cohort), an unresolved discrepancy flagged in both notes (2023-padhan-meta-analysis-rheumatic-diseases-rls.md vs 2008-stehlik-fibromyalgia-rls-prevalence.md).

Mechanistic picture in 5 bullet points

1. Brain iron deficiency is a convergent final pathway reached by multiple different upstream routes in secondary RLS: uremic/CKD physiology, third-trimester fetal iron demand in pregnancy, malabsorption in celiac disease, and straightforward blood-loss/nutritional iron-deficiency anemia all lower iron available to dopaminergic circuits, even though the celiac data show this is not the whole story in every comorbidity (2025-elangovan-ckd-dialysis-iron-prevalence.md, 2018-chen-pregnancy-prevalence-meta-analysis.md, 2010-moccia-celiac-rls-prevalence.md, 2016-kolukisa-iron-deficiency-anemia-rls-prevalence.md).
2. Neurodegenerative and demyelinating CNS disease can unmask or amplify RLS by disrupting the A11 diencephalospinal dopaminergic pathway and spinal sensorimotor circuits: RLS is a genuine prodromal feature of Parkinson disease (OR 4.19 even 5-10 years pre-diagnosis) and is markedly more prevalent in multiple sclerosis (28% vs 8%), plausibly linked in a subset of cases to spinal cord demyelination (2023-schrag-parkinson-prodromal-risk-factors.md, 2022-zali-meta-analysis-multiple-sclerosis-rls.md).
3. Chronic systemic inflammation, independent of primary iron or renal pathology, appears to sensitize sensorimotor and pain-processing circuits: rheumatic/autoimmune diseases (rheumatoid arthritis, lupus, ankylosing spondylitis) and fibromyalgia all show markedly elevated RLS prevalence in a dedicated meta-analysis (2023-padhan-meta-analysis-rheumatic-diseases-rls.md).
4. A shared dopaminergic/iron-linked neurodevelopmental and psychiatric vulnerability plausibly links RLS to ADHD across the lifespan (pediatric 11-54%, adult 33% with parallel iron deficiency) and to mood/suicide risk (anxiety/depression severity correlating with RLS severity; independently elevated suicide/self-harm risk not explained away by comorbid depression) (2025-ghayad-systematic-review-adhd-pediatric-rls.md, 2019-lopez-adult-adhd-iron-deficiency-rls.md, 2019-zhuang-suicide-self-harm-risk-rls.md).
5. Peripheral, non-CNS mechanisms also produce an RLS-like clinical picture: venous reflux (relieved by sclerotherapy/laser ablation in 80-98% of treated cases) and small-fiber, acquired/dysimmune peripheral neuropathy demonstrate that "RLS" as a diagnostic label captures at least one mechanistically distinct peripheral phenotype that can respond to purely local, non-dopaminergic, non-CNS treatment (1995-kanter-sclerotherapy-varicose-veins-rls.md, 2008-hayes-endovenous-laser-ablation-rls.md, 2006-gemignani-polyneuropathy-rls.md).

Implications for a non-drug long-term plan for people currently on dopamine agonists or alpha-2-delta ligands

• Screen broadly and specifically for the comorbidities in this topic (ferritin/TSAT regardless of trigger; HbA1c/fasting glucose; blood pressure; mood and suicide-risk screening; sleep-apnea screening if snoring or witnessed apneas; venous duplex ultrasound if visible varicose veins) as part of any long-term re-evaluation, since several of these are independently treatable and some (venous insufficiency, transplantable CKD, celiac disease, OSA) can meaningfully reduce RLS burden without touching the RLS drug regimen at all.
• Where the underlying condition itself can be treated definitively (kidney transplantation, venous ablation/sclerotherapy, CPAP for significant OSA, gluten-free diet and disease control for celiac, disease-modifying therapy for inflammatory rheumatic disease), pursue that treatment as a parallel or prior step to tapering dopamine-agonist or gabapentinoid doses, under physician supervision, rather than assuming RLS drugs alone must carry the full symptom burden indefinitely.
• In pregnancy-onset RLS, default to iron-first, non-dopaminergic management given both the pregnancy drug-avoidance context and the fact that most cases resolve toward the 4% postpartum baseline; do not anchor a lifelong dopamine-agonist regimen to a case that began in, and may resolve after, pregnancy without reassessment.
• In neurological comorbidities (Parkinson disease, MS), combine RLS-specific care with disease-specific non-drug measures (e.g., the MS-targeted physical-activity intervention already in this knowledge base, 2021-cederberg-physical-activity-ms-pilot-rct.md) and heightened clinical monitoring (RLS as a PD prodrome), since dose escalation of the same dopaminergic drug class used for RLS carries compounded augmentation and motor-complication risk in these populations.
• Treat psychiatric comorbidity assertively and continuously, not only at diagnosis: screen for depression, anxiety, and specifically suicide/self-harm risk throughout any medication change, since the RLS-suicide association is not fully explained by comorbid depression and may be heightened during periods of worsened symptom control (e.g., during a taper).
• Address modifiable cardiometabolic risk (weight, smoking cessation, alcohol moderation, physical activity, glycemic and blood-pressure control) as standard, evidence-supported adjunct care, while communicating the Katsanos 2017 nuance honestly: current confounder-adjusted evidence does not show RLS independently causes cardiovascular events, only an association with all-cause mortality, so cardiometabolic risk reduction should be framed as good general practice rather than a proven RLS-specific cardioprotective intervention.
• For comorbid insomnia, offer CBT-for-insomnia as a non-drug, evidence-supported adjunct rather than defaulting to added sedative-hypnotics on top of an existing dopamine-agonist or gabapentinoid regimen.

Open questions

• No randomized trial has tested whether treating a specific comorbidity (CPAP for OSA, sclerotherapy for venous insufficiency, biologic therapy for autoimmune disease, transplantation timing in CKD) durably reduces or eliminates the need for dopamine-agonist or gabapentinoid therapy in comorbid RLS; essentially all evidence here is observational or small/uncontrolled.
• The operative mechanism behind kidney-transplant RLS remission (uremic toxin clearance vs. improved iron/erythropoietin status vs. other physiological change) has never been isolated (2002-winkelmann-kidney-transplant-reverses-rls.md).
• Causal direction is unresolved for most cross-sectional comorbidity associations in this topic (migraine, diabetes, mood disorders, ADHD); prospective, ideally treatment-intervention, studies are needed.
• The fibromyalgia RLS-prevalence discrepancy (38.1% meta-analytic pooled vs. 64% in one cohort) has not been resolved by a large, harmonized-methodology study.
• Whether correcting venous insufficiency (sclerotherapy/ablation) works via a genuinely local vascular mechanism, via incidental iron/inflammation effects, or via a large placebo response has never been tested in a sham-controlled trial.
• Long-term (multi-year) outcomes of non-pharmacological, comorbidity-directed RLS management specifically in high-comorbidity-burden populations (CKD, PD, MS) during a supervised dopamine-agonist taper are essentially absent from the published literature.

Notes in this topic

• 1995-kanter-sclerotherapy-varicose-veins-rls.md - 22% RLS prevalence in a vein clinic; sclerotherapy gave 98% initial relief.
• 2008-hayes-endovenous-laser-ablation-rls.md - Laser ablation + sclerotherapy cut mean IRLS severity ~80%.
• 2002-winkelmann-kidney-transplant-reverses-rls.md - Kidney transplant resolved RLS in 11/11 hemodialysis patients within 1-21 days.
• 2025-elangovan-ckd-dialysis-iron-prevalence.md - RLS prevalence by CKD modality (HD 51.7%, transplant 23.8%); iron indices significantly worse with RLS.
• 2023-padhan-meta-analysis-rheumatic-diseases-rls.md - Meta-analysis: RLS prevalence 26.6-38.1% across rheumatic diseases/fibromyalgia.
• 2008-stehlik-fibromyalgia-rls-prevalence.md - 64% RLS prevalence in a female fibromyalgia cohort; worse sleep with comorbid RLS.
• 2022-zali-meta-analysis-multiple-sclerosis-rls.md - Meta-analysis (75 studies): 28% pooled RLS prevalence in MS vs 8% controls.
• 2022-sevim-ms-rls-anxiety-depression.md - Comorbid RLS in MS significantly raises anxiety/depression scores.
• 2004-sevim-population-anxiety-depression-rls.md - Population survey: RLS severity correlates with anxiety/depression severity.
• 2014-becker-mood-disorders-review.md - Narrative review of 32 epidemiologic studies linking RLS to mood disorders.
• 2019-wang-migraine-meta-analysis.md - Meta-analysis: 17% RLS prevalence in migraineurs vs 7% controls.
• 2024-kim-osa-rls-depression-insomnia.md - 16.1% RLS in OSA; severity inversely related to apnea severity.
• 2025-tam-co-rosa-systematic-review.md - Systematic review: 10-30% RLS-OSA comorbidity; CPAP often helps, sometimes triggers PLMS.
• 2018-akin-type2-diabetes-rls-prevalence.md - 28.3% RLS prevalence in type 2 diabetes, rising with duration and insulin use.
• 2013-winter-vascular-risk-factors-rls-men.md - Large physician cohort: diabetes and stroke raise RLS odds; prior MI paradoxically lowers it.
• 2023-schrag-parkinson-prodromal-risk-factors.md - Very large case-control: RLS as a Parkinson disease prodromal marker (OR 4.19).
• 2019-zhuang-suicide-self-harm-risk-rls.md - Large cohort: RLS independently doubles suicide/self-harm risk.
• 2018-chen-pregnancy-prevalence-meta-analysis.md - Meta-analysis (27 studies): 21% pooled pregnancy RLS prevalence, falling to 4% postpartum.
• 2019-lopez-adult-adhd-iron-deficiency-rls.md - 33% RLS prevalence in adult ADHD, with parallel iron deficiency.
• 2021-manconi-nature-reviews-disease-primer.md - Disease-primer review situating comorbidity (iron, kidney, cardiovascular, diabetes) within overall RLS pathophysiology.
• 2016-kolukisa-iron-deficiency-anemia-rls-prevalence.md - 41.1% RLS prevalence in women with (non-renal, non-pregnancy) iron deficiency anemia.
• 2017-yildiz-obesity-risk-factor-rls.md - Case-control: RLS correlates with obesity; obese patients also have more depression/anxiety/insomnia.
• 2023-safarpour-ckd-rls-systematic-review.md (pre-existing) - Systematic review: 15-30% RLS prevalence in CKD/dialysis.
• 2026-hackethal-life-on-pregnancy-rls-cohort.md (pre-existing) - Prospective cohort: 26% antenatal, 34.7% cumulative pregnancy RLS incidence.
• 2026-winkelman-rls-jama-clinical-review.md (pre-existing) - 2026 JAMA review; comorbidity prevalence figures (MS 27.5%, ESKD 24%, iron-deficiency anemia 23.9%, pregnancy 22%, peripheral neuropathy 21.5%, PD 20%).
• 2025-ghayad-systematic-review-adhd-pediatric-rls.md (pre-existing) - Systematic review: 11-54% RLS prevalence in pediatric ADHD.
• 2010-moccia-celiac-rls-prevalence.md (pre-existing) - 31% RLS prevalence in celiac disease vs 4% controls; not iron-explained.
• 2006-gemignani-polyneuropathy-rls.md (pre-existing) - 30% RLS prevalence in polyneuropathy, especially small-fiber/acquired.
• 2007-gemignani-diabetic-neuropathy-rls.md (pre-existing) - RLS in diabetic peripheral neuropathy.
• 2017-shen-meta-analysis-hypertension-risk.md (pre-existing) - Meta-analysis: pooled hypertension OR 1.36 in RLS.
• 2018-huang-plms-cardiovascular-meta-analysis.md (pre-existing) - Meta-analysis: PLMS-coronary artery disease OR 1.57.
• 2017-katsanos-meta-analysis-cardiovascular-mortality.md (pre-existing) - Meta-analysis: after adjustment, RLS linked only to all-cause mortality (HR 1.52), not CV events.
• 2016-molnar-veterans-cohort-mortality-comorbidity.md (pre-existing) - Veteran cohort: very large mortality and CHD/stroke/CKD hazard ratios (upper-bound estimate).
• 2018-shin-plms-hypertension-negative.md (pre-existing) - Negative finding: PLMS not associated with hypertension in a Korean clinical cohort.
• 2020-song-cbti-rls-comorbid-insomnia-rct.md (pre-existing) - RCT: CBT-for-insomnia improves sleep in RLS+insomnia patients.
• 2017-kolla-antidepressants-rls-systematic-review.md (pre-existing) - Systematic review: mirtazapine raises RLS/PLM risk; bupropion may help.
• 2020-didriksen-gwas-three-novel-variants.md (pre-existing) - GWAS/polygenic risk score: obesity, smoking, alcohol share genetic liability with RLS.
• 2016-batool-anwar-lifestyle-factors-cohort.md (pre-existing) - Prospective cohort: healthy lifestyle factors (weight, activity, non-smoking) lower RLS risk.
• 2021-cederberg-physical-activity-ms-pilot-rct.md (pre-existing) - Pilot RCT: physical-activity intervention improves RLS severity in comorbid MS.
• 2019-calzetti-small-fiber-premotor-parkinson.md (pre-existing) - Case series: small-fiber pathology underlying RLS in pre-motor Parkinson disease.

Additional linked notes (2026-09 quality pass)

These notes carry this topic tag but are not yet woven into the prose synthesis above; listed here so they are discoverable and counted in catalog.json rather than orphaned.

• 2006-novak-kidney-transplant-insomnia-rls-hungary.md (2006) - Chronic insomnia in kidney transplant recipients: In this Hungarian cross-sectional comparison, insomnia (Athens Insomnia Scale) prevalence was 15% in wait-listed dialysis patients versus only 8% in kidney transplant recipients (p<0.001) - statistically indistinguish...
• 2009-szentkiralyi-rls-depression-ckd-hungary.md (2009) - Association between restless legs syndrome and depression in patients with chronic kidney disease: In this Budapest cross-sectional study of 949 chronic kidney disease patients, probable RLS was strongly associated with depressive symptoms: 56% of patients with RLS had depressive symptoms versus 22% without RLS (p<...
• 2011-gjerstad-parkinsons-leg-restlessness-cohort.md (2011) - Increased risk of leg motor restlessness but not RLS in early Parkinson disease: In a Norwegian population-based incident cohort of 200 drug-naive early Parkinson disease (PD) patients versus 173 matched controls, leg motor restlessness (LMR) not meeting full RLS criteria was nearly 3-fold more co...
• 2013-azmin-rls-parkinsons-disease-malaysia.md (2013) - Restless legs syndrome and its associated risk factors in Parkinson's disease: In a cross-sectional Malaysian cohort of 113 idiopathic Parkinson's disease (PD) patients, RLS prevalence was 9.7% (using IRLSSG criteria), broadly consistent with global PD-RLS prevalence estimates, and was significa...
• 2015-chatterjee-somatoform-pain-rls-prevalence.md (2015) - Prevalence of restless legs syndrome in somatoform pain disorder and its effect on quality of life: Among 192 patients with persistent somatoform pain disorder (SPD) screened using IRLSSG criteria, RLS prevalence was 28%, substantially higher than general-population estimates; RLS co-occurrence was associated with a...
• 2015-schlesinger-rls-stroke-israel.md (2015) - Restless legs syndrome in stroke patients: In an in-hospital case-control study at Rambam Health Care Campus (Haifa, Israel), 22 of 149 acute stroke/TIA patients (15%) had RLS versus 10 of 298 frequency-matched controls (3%) (p < 0.0001). After adjusting for c...
• 2015-sinniah-magnesium-deficiency-hemodialysis-rls.md (2015) - Magnesium deficiency: a possible cause of restless leg syndrome in haemodialysis patients: This letter, authored from the International Medical University Clinical School in Seremban, Malaysia, proposes magnesium deficiency as a possible contributing cause of RLS in hemodialysis patients, commenting on a pr...
• 2015-ylikoski-parkinson-insomnia-rls-finland.md (2015) - Parkinson's disease and insomnia: In a large questionnaire-based survey of Finnish Parkinson's disease (PD) patients, chronic inability to sleep (insomnia) had a prevalence of 36.9% (95% CI 33.3-40.5). In logistic regression models, restless legs synd...
• 2016-bathla-hemodialysis-wed-prevalence-india.md (2016) - Prevalence and correlates of Willis-Ekbom's disease/restless legs syndrome in patients undergoing hemodialysis: In 194 adult maintenance hemodialysis patients (mean age 54.4+-15, 58.2% male), Willis-Ekbom disease/RLS (diagnosed by IRLSSG criteria on face-to-face interview) had a prevalence of 5.2%, higher than typical general-p...
• 2016-sieminski-nocturnal-blood-pressure-rls.md (2016) - Nocturnal systolic blood pressure is increased in restless legs syndrome: In this retrospective polysomnography cohort from the Medical University of Gdansk, patients with RLS had significantly higher nocturnal and sleep-time systolic blood pressure than matched controls, and lacked the nor...
• 2017-auvinen-depression-restless-legs-finland.md (2017) - Prevalence of restless legs symptoms according to depressive symptoms and depression type: a cross-sectional study: In Finnish primary care, restless legs symptom prevalence rose steadily with the severity of depressive symptoms: 24.6% in psychiatrically healthy controls, 43.4% in those with elevated depressive symptoms but no form...
• 2018-tkachuk-pramipexole-zopiclone-diabetic-polyneuropathy.md (2018) - Aktyhrafiya dlya otsinky efektyvnosti terapiyi u khvorykh iz syndromom nespokiynykh nih na tli diabetychnoyi polinevropatiyi (Actigraphy for assessing therapy effectiveness in restless legs syndrome patients with diabetic polyneuropathy): In 43 Ukrainian patients with diabetic-polyneuropathy-associated RLS who had failed gabapentin, add-on zopiclone to pramipexole outperformed pramipexole monotherapy on both motor (actigraphy-measured periodic limb mov...
• 2019-bhagawati-ckd-stages-wed-severity.md (2019) - Impact of different stages of chronic kidney disease on the severity of Willis-Ekbom disease: In 300 CKD patients, Willis-Ekbom disease (WED, i.e., RLS) prevalence was 20% overall, was significantly more common in patients on maintenance hemodialysis than in conservatively managed CKD (p=0.0001), and both pres...
• 2019-serranova-fmd-rls-case-control-czech.md (2019) - Prevalence of restless legs syndrome in functional movement disorders: a case-control study from the Czech Republic: In this Prague case-control study, RLS diagnostic criteria were met in 43.8% of patients with functional movement disorders (FMD) (95% CI 34-54%) versus 7.9% of matched controls (95% CI 3-17%), p<0.00001. Actigraphy-c...
• 2019-zhang-rls-ischemic-stroke-cohort-china.md (2019) - Restless legs syndrome in ischemic stroke patients: clinical features and significance: Among 199 Chinese ischemic stroke patients assessed by polysomnography, 11.1% (22/199) had RLS, and low serum ferritin, subcortical infarction, and female sex were independent risk factors; RLS was associated with wor...
• 2020-auvinen-musculoskeletal-pain-depression-rls.md (2020) - The influence of restless legs symptoms on musculoskeletal pain in depression: In this Finnish primary-care cross-sectional study, restless legs symptoms were associated with continuous widespread musculoskeletal pain in controls without depression (10.5% vs 2.3% without RLS symptoms, p=0.001) a...
• 2020-srifuengfung-rls-adhd-thai-children.md (2020) - Restless legs syndrome in children and adolescents with attention-deficit/hyperactivity disorder: prevalence, mimic conditions, risk factors, and association with functional impairment: In a Thai prospective cohort of 217 children/adolescents with ADHD, RLS (2012 revised IRLSSG criteria) was found in 11%, with an additional 23% having RLS-mimic conditions (mostly myalgia and habitual foot tapping); a...
• 2021-gitai-sca3-ataxia-iron-deficiency.md (2021) - Which Factors in Spinocerebellar Ataxia Type 3 Patients Are Associated with Restless Legs Syndrome/Willis-Ekbom Disease?: RLS/Willis-Ekbom disease was found in 27.5% of Brazilian SCA3 (Machado-Joseph disease) patients versus 2.5% of controls (p=0.003); among SCA3 patients, RLS was associated with female sex, later ataxia symptom onset (a...
• 2021-hasan-sleep-disorders-stroke-meta-analysis.md (2021) - Dynamic Prevalence of Sleep Disorders Following Stroke or Transient Ischemic Attack: Systematic Review and Meta-Analysis: This systematic review and meta-analysis (169 studies, 64,047 adults), co-authored by researchers from Politeknik Kesehatan Kemenkes Malang and Universitas Muhammadiyah Malang, Indonesia, found pooled RLS prevalence o...
• 2021-ozdogar-rls-multiple-sclerosis-metaanalysis.md (2021) - Restless legs syndrome in people with multiple sclerosis: An updated systematic review and meta-analyses: This updated systematic review and meta-analysis, co-authored by Alon Kalron (Tel-Aviv University / Sheba Medical Center MS Center, Israel), searched MEDLINE, Scopus and EMBASE through April 2021 and pooled 19 studies...
• 2021-sobreira-neto-parkinson-rls-factors-brazil.md (2021) - Is restless legs syndrome in Parkinson disease patients associated with any specific factor?: In this Brazilian cross-sectional study of 88 Parkinson disease patients, 25 (28.4%) had comorbid RLS; on multivariate analysis, RLS in Parkinson disease was independently associated with smell loss (anosmia) and wors...
• 2022-plotogea-rls-liver-cirrhosis.md (2022) - The Prevalence and Predictors of Restless Legs Syndrome in Patients with Liver Cirrhosis: In a 14-month prospective cross-sectional study of 69 patients with liver cirrhosis at a Bucharest hospital, 55% met IRLSSG criteria for RLS. Age, diabetes, cirrhosis severity, serum creatinine, glomerular filtration ...
• 2023-diaconu-rls-parkinsons-romania.md (2023) - Restless Legs Syndrome in Parkinson's Disease: In a cross-sectional cohort of 131 people with Parkinson's disease treated at County Clinic Hospital Braşov, Romania, 35 patients (26.71%) met RLS diagnostic criteria, with no significant sex difference (p = 0.431). P...
• 2023-prajjwal-ms-fatigue-rls-review.md (2023) - Association of multiple sclerosis with chronic fatigue syndrome, restless legs syndrome, and various sleep disorders, along with the recent updates: This international multi-author narrative review (one co-author affiliated with Lugansk State Medical University, Ukraine) discusses overlap between multiple sclerosis (MS), myalgic encephalomyelitis/chronic fatigue s...
• 2024-chen-acupuncture-hemodialysis-taiwan.md (2024) - Efficacy and Safety of Acupuncture for Restless Legs Syndrome in Patients with End-Stage Renal Disease: A Randomized-Controlled Trial at Hospital-Based Hemodialysis Center: A single-blind Taiwanese RCT found that 4 weeks of acupuncture (12 sessions) significantly improved RLS severity and insomnia in end-stage renal disease patients undergoing hemodialysis, with a parallel shift in heart...
• 2024-kniazeva-medication-overuse-headache-rls-cohort.md (2024) - Sleep disorders in patients with medication-overuse headache: In this Yekaterinburg prospective case-control study, RLS was significantly more common in patients with medication-overuse headache than in headache patients without overuse (37.4% vs 22.0%, p=0.002, OR 2.1, 95% CI 1...
• 2024-park-psmd-small-vessel-disease-korea.md (2024) - Small vessel disease in patients with restless legs syndrome evidenced by elevated peak width of skeletonized mean diffusivity: Korean RLS patients showed significantly higher peak width of skeletonized mean diffusivity (PSMD), a novel cerebral small-vessel-disease marker, than healthy controls, and PSMD rose with increasing RLS severity — sug...
• 2024-partinen-covid-rls-icoss-survey.md (2024) - Restless legs symptoms increased during COVID-19 pandemic. International ICOSS-survey: In this Helsinki-led international online survey (ICOSS consortium), self-reported restless legs symptoms (3+ evenings/nights per week) were significantly more common during the COVID-19 pandemic (9.1%, 95% CI 8.7-10....
• 2024-tam-sleep-disturbances-parkinsons-vietnam.md (2024) - Sleep disturbances and associated factors in patients with Parkinson's disease: In a Vietnamese cross-sectional cohort of 130 Parkinson's disease patients, 90.9% had a sleep disorder, with insomnia (76.2%) and restless legs syndrome (56.2%) the most common types; shoulder and neck pain was the on...
• 2024-vanderham-adhd-sleep-problems-netherlands.md (2024) - Sleep Problems in Adults With ADHD: Prevalences and Their Relationship With Psychiatric Comorbidity: In this large Dutch outpatient ADHD cohort, screening with the Holland Sleep Disorders Questionnaire found RLS/periodic limb movement disorder (PLMD) symptoms in 29% of adults with ADHD — the third most prevalent slee...
• 2025-anupama-esrd-hemodialysis-psychosocial-india.md (2025) - Prevalence, Risk Factors, and Psychosocial Impact of Restless Legs Syndrome in End-Stage Renal Disease Patients Undergoing Hemodialysis - A Cross-Sectional Study: Among 308 Indian hemodialysis patients, RLS was identified in 14.9% (46 patients), most with mild-to-moderate severity, and was associated with significantly greater anxiety, depression, and poor sleep quality (97.8% ...
• 2025-kim-rls-erectile-dysfunction-korea.md (2025) - Association between restless legs syndrome and erectile dysfunction in Korean men: A cross-sectional study: Treatment-naive Korean men with moderate-to-severe RLS had markedly worse erectile function than matched controls, with erectile dysfunction (ED) prevalence of 78.7% in the RLS group versus 52.5% in controls, and ED s...
• 2025-nepozitek-functional-motor-disorder-rls-polysomnography.md (2025) - Sleep in Functional Motor Disorders: A Case-Control Polysomnographic Study: In this Prague case-control polysomnographic study, 32% of patients with functional motor disorders (FMD) had restless legs syndrome, alongside 38% with clinically significant obstructive sleep apnoea and 8% with peri...
• 2025-nguyen-rls-psoriasis-vietnam.md (2025) - Restless Legs Syndrome in Psoriasis: A Multicenter Study on Its Prevalence, Severity, and Impact on Patients: In a multicenter Vietnamese case-control study (106 psoriasis patients vs. 106 healthy controls), RLS prevalence was significantly higher in psoriasis patients, and among psoriasis patients, those with RLS had signifi...
• 2025-raasing-sarcoidosis-small-fiber-neuropathy-rls.md (2025) - Sarcoidosis-related small fiber neuropathy: Focus on fatigue, pain, restless legs syndrome, and cognitive function: In this Dutch case-control study, RLS was present in 67% of sarcoidosis patients with small fiber neuropathy (SFN), and RLS severity was significantly higher in the sarcoidosis-with-SFN group than in sarcoidosis patie...
• 2025-tinh-stroke-related-rls-vietnam.md (2025) - Stroke-related restless leg syndrome in hemorrhagic and ischemic stroke patients: In a Vietnamese cohort of 423 MRI-confirmed stroke patients, RLS (diagnosed 1 month post-stroke per IRLSSG criteria) occurred in 11.6% overall — 13.1% after ischemic and 8.6% after hemorrhagic stroke — and was more fr...
• 2026-cucu-rls-sleep-quality-ms.md (2026) - Machine Learning-Based Prediction of Sleep Quality in Patients with Multiple Sclerosis: In a cross-sectional cohort of 173 people with multiple sclerosis (mean age 39.66 ± 11.86 years, 90.2% relapsing-remitting MS) treated in Iasi, Romania, 48.0% were classified as poor sleepers (PSQI > 5; mean PSQI 6.06...
• 2026-hu-sanjiao-acupuncture-massage-hemodialysis.md (2026) - Sanjiao acupuncture combined with abdominal massage for restless legs syndrome in maintenance hemodialysis patients: A randomized controlled trial: In a single-center Chinese RCT in hemodialysis patients, adding abdominal massage to Sanjiao acupuncture produced a higher responder rate and lower endpoint IRLS scores than acupuncture alone, though both groups impro...
• 2026-petrakis-rls-hiv-greece.md (2026) - Restless leg syndrome in people living with HIV: Prevalence, clinical predictors and the impact on sleep quality and psychological distress: In a cross-sectional study of 194 Greek people living with HIV and 200 HIV-negative controls, RLS prevalence was significantly higher in PWHIV (31%, 95% CI 25.3–38.3%) than controls (15%, 95% CI 10.2–20.2%, p < 0.001)...